Side effects, long term outcomes, and head to head comparisons for suppressive and device based contraception.
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Mayo Clinic, 2025 Mayo Clinic
Mayo Clinic patient overview of vasectomy, a permanent male contraceptive procedure that cuts and seals the vas deferens. Covers indications, the no-scalpel technique, risks, recovery, and semen testing. Notes vasectomy reversal and IVF are possible after vasectomy but are harder, costly, and not guaranteed, so vasectomy should be considered permanent. By Mayo Clinic Staff, updated March 7, 2025.
Yonis H et al., 2025 BMJ Open Access
To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction. Real-world, nationwide, prospective cohort study. Denmark, by use of national registries. All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy. First time diagnosis of ischaemic stroke or myocardial infarction at discharge. Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction). Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.
Hemmingsen CH et al., 2024 Eur J Cancer
Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information. Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤ 3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use. During 29,455,528 person-years, 1701 children developed leukemia (no use: 518, previous use: 974, recent use: 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95 % CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95 % CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95 % CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95 % CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95 % CI 1.28-3.44). Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products.
Letnar G et al., 2024 Stroke
The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke. In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30-40versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized. In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62-1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30to 40and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50-0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97-1.35]). Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.
Mengelkoch S et al., 2024 Brain, behavior, and immunity
Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.
Meaidi A et al., 2023 BMJ (Clinical research ed.)
To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. Nationwide cohort study. Denmark through national registries. All 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065). A first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism. Among 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception. NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.
Noachtar IA et al., 2023 JAMA network open
Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation. To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs. DESIGN, SETTING, This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria. COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses. Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed. A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause. In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.
Mosorin ME et al., 2023 Acta Obstet Gynecol Scand Open Access
Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. MATERIAL AND This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.
Johansson T et al., 2023 Epidemiol Psychiatr Sci Open Access
Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.
Davidson AV et al., 2023 Kans J Med Open Access
Evidence-based, nonbiased, counseling on contraceptive options, followed by shared decision-making, is key in facilitating reproductive justice in a diverse population. An estimated 3% of contraceptive users in the United States use fertility awareness-based methods (FABMs) for contraception, and demand for these methods is increasing. FABMs can be a highly effective form of family planning when used in accordance with evidence-based protocols. They are preferred by some patients due to medical contraindications to hormonal contraceptives, lack of side effects, religious convictions, preference to avoid hormones or contraceptive devices, improved body literacy, or a combination of the above. FABMs are infrequently covered in medical school curricula and are often perceived by physicians to be of low efficacy. There is an opportunity for improvement of physicians' evidence-based knowledge of FABMs, which has the potential to improve patient understanding of and access to the full menu of family planning options. A self-administered, cross-sectional survey was distributed to assess physician knowledge and opinions of FABMs by key university contacts. Univariate and bivariate statistics were calculated for close-ended questions and responses to open-ended questions were analyzed for common themes. A total of 79 participants completed the entire survey. Another 11 submitted partially completed surveys. For completed surveys, questions assessing knowledge of key concepts underlying FABMs, performance by specialty was 55% correct for OB/GYN (n = 16), 55% (n = 47) correct for family medicine, 36% (n = 10) correct for internal medicine, and 35% (n = 6) correct for pediatrics. Negative, neutral, mixed, and positive opinions related to FABMs were represented. There are opportunities to improve physicians' evidence-based knowledge of FABMs; this may improve patient-centered contraceptive care.
Kazmerski TM et al., 2023 J Cyst Fibros
As survival and health improve in people with cystic fibrosis (CF), more women with CF (wwCF) are considering their sexual and reproductive health (SRH). This study compared SRH experiences, behaviors, and care utilization of wwCF to the general population and defined CF-impacted considerations and care preferences. We surveyed wwCF aged ≥25 years regarding SRH and compared results to the US National Survey of Family Growth (NSFG;n = 4357) and friend controls(n = 123). We used descriptive statistics and chi-squared/Fisher's exact testing and linear regression for comparisons. A total of 460 wwCF (mean age 36.1 years) completed the survey. WwCF were less likely to report current contraceptive use (43%vs76% NSFG, p<0.001;60% friends, p = 0.005). Nearly 25% of wwCF reported worsened CF symptoms during their menstrual cycles, 50% experienced urinary incontinence, and 80% vulvovaginal candidiasis. WwCF were significantly less likely to be parents (46%vs62% friends, p = 0.015) and to have experienced pregnancy (37%vs78% NSFG, p<0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p<0.001 and 5% friends, p<0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p<0.001). WwCF report suboptimal rates of contraceptive and preconception counseling/care and are less likely to have received HPV vaccination (42%vs55%friends, p = 0.02). Despite desiring SRH conversations with their CF team, <50% report discussing SRH topics. WwCF have significantly different SRH experiences than non-CF peers. They report suboptimal SRH care compared to their preferences highlighting an urgent need to encourage SRH counseling/care in the CF model.
Latack KR et al., 2022 Contraception
To examine trends in national reporting of broken intrauterine devices (IUDs). We enumerated IUD device "breakage" reports in the Food and Drug Administration Adverse Event Reporting System from inception (1998) until February 2022. We explored associations of breakage with IUD type (copper versus hormonal), year reported, reporter (consumer versus clinician), and patient characteristics (age and weight). We identified 4144 breakage reports for copper versus 2140 for hormonal IUDs. Among the 170,215 adverse events reported, breaks were disproportionately reported for copper (9.6%) versus hormonal (1.7%) IUDs. National pharmacovigilance data suggests disproportionate breakage in copper versus hormonal IUDs though the true prevalence of breaks cannot be calculated from this dataset.
Jensen JT et al., 2022 Contraception Open Access
To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen. We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors. Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m(2). The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m(2), 25 to 29.9 kg/m(2), and ≥30 kg/m(2) of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception. E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable. Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.
Elgemark K et al., 2022 Obstetrics and gynecology
To assess the Pearl Index for risk of ectopic pregnancy in women using levonorgestrel-releasing intrauterine systems (LNG-IUS) with hormonal reservoirs of 13.5 mg, 19.5 mg, or 52 mg. This was a retrospective cohort study. Women diagnosed with an ectopic pregnancy in Stockholm County, Sweden, between January 1, 2014, and December 31, 2019, were identified through the electronic medical record system. The final analysis included 2,252 cases of ectopic pregnancy. Information on age, reproductive and medical history, as well as current use of contraception was retrieved. The time of intrauterine device (IUD) insertion before ectopic pregnancy and the numbers of sold LNG-IUS during the study period were used to calculate the incidence rate for ectopic pregnancy during use per 100 woman-years (Pearl Index). Among women with an ectopic pregnancy diagnosis, 105 presented with a known type of hormonal IUD in situ, of whom 94 were included in the calculations of the Pearl Index. The estimated Pearl Index for ectopic pregnancy was 0.136 (95% CI 0.106-0.176) for the LNG-IUS 13.5-mg, 0.037 (95% CI 0.021-0.067) for the LNG-IUS 19.5-mg, and 0.009 (95% CI 0.006-0.014) for the LNG-IUS 52-mg. With the 52-mg LNG-IUS as referent, the relative risk (RR) for ectopic pregnancy was higher during the first year for LNG 13.5-mg (RR 20.59, 95% CI 12.04-35.21), and for both 13.5-mg (RR 14.49, 95% CI 9.01-23.3) and 19.5-mg (RR 4.44, 95% CI 1.64-12.00) during the total study period. The absolute risk of ectopic pregnancy during the use of LNG-IUS at any doses was low. The results show that the lower the dose of the IUD, the higher the risk of an ectopic pregnancy. Higher-dose LNG-IUS should be considered when providing contraceptive counseling to a woman with known risk factors for ectopic pregnancy who are considering a hormonal IUD.
Mu E et al., 2022 Australian prescriber
Hormonal contraception is known to precipitate or perpetuate depression in some patients. The link between oral contraceptive pills and depression relates to the amount and type of progestogen contained in these pills. Many of the older oral contraceptive pills, which contain ethinylestradiol, are linked to severe mood problems. Newer oral contraceptive pills containing physiological forms of oestrogen may be better tolerated with a purported weaker link to mood problems. Clinicians should consider the temporal relationship between the use of hormonal contraception and development of new or worsened depression or mood changes.
Hua X et al., 2022 Journal of medical microbiology Open Access
Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.
He B et al., 2022 Eye (London, England) Open Access
Hormonal contraceptives (HCs) are a known risk factor for dry eye disease (DED), yet the relationship between HCs use and DED in women of child-bearing age remains debatable. The aim of this study was to determine the association between HCs and DED in females of reproductive age. This was a retrospective cohort study using data from IQVIA's electronic medical record (IQVIA, USA). 4,871,504 women (age 15-45) between 2008 and 2018 were followed to the first diagnosis of DED as defined by an ICD-9/10 code. DED cases also required at least two prescriptions of cyclosporine or lifitegrast topical drops within 60 days of the first code. The date of the first code was designated as the index date. Regular HCs users needed to have at least two prescriptions in both the first year and second year prior to the index date. For each case, five controls were selected and matched to cases by age and follow-up time. A conditional logistic regression model was used to adjust for confounders of DED and to calculate odds ratios (ORs). HCs users were at a higher risk for DED than non-users. Regular users of HCs were more likely to develop DED (ORs = 2.73, 95% CI [2.21-3.73]) than irregular users. Those who used a greater number of HCs were at a higher risk for DED. This study indicates an increased risk of DED with HCs use in women of child-bearing age.
Pasvol TJ et al., 2022 Alimentary pharmacology & therapeutics
How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described. To examine associations between types of hormonal contraception and development of IBD. This was a nested case-control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated. 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively). We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.
Khondoker CC et al., 2022 Reprod Health Open Access
Multiple contraindications to combined hormonal contraceptives (CHC) use exist. The impact of these factors on contraceptive choice, particularly among women living with HIV (WLWH), is not well understood. We measured and compared the prevalence of contraceptive use and contraindications among WLWH and women not living with HIV (controls). We examined cross-sectional survey and medical chart data from 83 WLWH and 62 controls, aged 16-49 and sexually active, from 2013-2017. We compared the age-adjusted prevalence and types of contraceptives used in the last month and the proportion of women with CHC contraindications, including drug interactions, medical comorbidities, and smoking at ≥ 35 years old. All WLWH received care at an interdisciplinary, women-centred HIV clinic. Compared to controls, WLWH were older (median [IQR)] 39 [34-43] vs 31 [23-41] years; p = 0.003), had less post-secondary education (37% vs 73%; p < 0.001), and more often had household income < $15,000/year (49% vs 30%; p = 0.006). WLWH trended to higher contraceptive prevalence than controls (80% vs 63%; p = 0.06 adjusted for age). Overall hormonal contraceptive use was similar. However, despite controlling for age, WLWH used CHC less (4% vs 18%; p = 0.006) than controls, and had more frequently undergone tubal ligation (12% vs 2%; p = 0.03). WLWH also experienced more CHC contraindications (54% vs 13%; p = 0.0001), including smoking at ≥ 35 years old (30% vs 6%; p = 0.0003) or a CHC-related drug interaction (all antiretroviral related) (25% vs 0%; p = 0.0001). WLWH attending our interdisciplinary clinic used hormonal contraception at similar rates as controls, though with different types. Differences may reflect different distributions of CHC contraindications. CHC contraindications present barriers to accessing the full range of contraceptive choices for WLWH. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed, especially when care is provided without the benefit of an interdisciplinary women-centered healthcare team.
Khafagy GM et al., 2021 Korean J Fam Med Open Access
Contraceptive agents are widely used by women of reproductive age, and resulting depression is the most common side effect of this usage. This study aimed to study the effect of monthly injectable combined contraceptives versus that of combined oral contraceptive pills (COC) on patients' mood. A prospective cohort study was conducted on 124 females aged 18-45 years attending the Kom-Ashfeen Family Medicine Unit, El-Kalyubia, Egypt. Participants were divided into three groups according to their choice: group A included 44 participants who received monthly combined injectable contraceptives (CIC); group B included 40 participants who took COC; and group C included 40 participants who used the copper intrauterine device (IUD). The Patient Health Questionnaire-9 (PHQ-9) score was assessed at the beginning of the study and after 6 months of follow-up. After 6 months of follow-up, there were mild but statistically significant increases in the PHQ-9 score in groups A and B, with group A (CIC users) showing the highest increase. Approximately 34.1%, 27.5%, and 15% of CIC, COC, and IUD users, respectively, moved from the non-depression stage to mild depression after 6 months; this change was statistically significant in groups A and B only. Monthly injectable combined contraceptives and oral contraceptive pills were associated with an increased risk of developing mild depression; this risk was higher in users of CICs, although the difference was not statistically significant. Thus, it is crucial to counsel patients about this possible risk and to follow them up. However, further studies are required to confirm our results.
Williams WV et al., 2021 Linacre Q
To investigate the sociological, environmental, and economic impact of hormonally active contraceptives, a series of comprehensive literature surveys were employed. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage, and an increase in divorce with deleterious effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality, and incarceration, among others. The environmental impact is discussed briefly and includes the feminization and trans-gendering of male fish downstream from the effluent of city wastewater treatment plants with declining fish populations. The potential economic impact of most of these side effects is estimated based on epidemiologic data and published estimates of costs of caring for the diseases which are linked to the use of hormonally active contraceptives. Hormonally active contraceptives appear to have a deleterious impact on multiple aspects of women's health as well as negative economic and environmental impacts. These risks can be avoided through the use of nonhormonal methods and need to be more clearly conveyed to the public. Hormonal contraceptives have wide-ranging effects. The potential economic impact of the medical side effects is estimated. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage and an increase in divorce with negative effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality and incarceration among others. The environmental impact includes hormonal effects on fish with declining fish populations. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free methods like Fertility Awareness Methods.
Morssinkhof MWL et al., 2021 Psychoneuroendocrinology Open Access
Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. This study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. Measurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. We included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not moderate the associations between OC use and depressive or insomnia symptoms. The study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between withinand between person-estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia.
Anderl C et al., 2021 J Child Psychol Psychiatry Open Access
Because of the widespread use of oral contraceptives (OCs) and the devastating effects of depression both on an individual and a societal level, it is crucial to understand the nature of the previously reported relationship between OC use and depression risk. Insight into the impact of analytical choices on the association is important when interpreting available evidence. Hence, we examined the association between adolescent OC use and subsequent depression risk in early adulthood analyzing all theoretically justifiable models. Data from the prospective cohort study TRacking Adolescents' Individual Lives Survey, among women aged 13-25 years were used. Adolescent OC use (ages 16-19 years) was used as a predictor and major depressive disorder (MDD) in early adulthood (ages 20-25 years), as assessed by the Diagnostic and Statistical Manual of Mental Disorders-IV oriented Lifetime Depression Assessment Self-Report and the Composite International Diagnostic Interview, was used as an outcome. A total of 818 analytical models were analyzed using Specification Curve Analysis in 534 adolescent OC users and 191 nonusers. Overall, there was an association of adolescent OC use and an episode of MDD in early adulthood [median odds ratio (OR)(median) = 1.41; OR(min) = 1.08; OR(max) = 2.18, p < .001], which was driven by the group of young women with no history of MDD (OR(median) = 1.72; OR(min) = 1.21; OR(max) = 2.18, p < .001). In summary, adolescent OC use was associated with a small but robust increased risk for experiencing an episode of MDD, especially among women with no history of MDD in adolescence. Understanding the potential side effects of OCs will help women and their doctors to make informed choices when deciding among possible methods of birth control.
Williams WV et al., 2021 Linacre Q
Hormonal contraceptives have been on the market for over fifty years and, while their formulations have changed, the basic mechanism of action has remained the same. During this time, numerous studies have been performed documenting side effects, some of which appear over time, some within weeks or months, but all can have a serious impact on health and quality of life. An effort was made to perform a series of comprehensive literature surveys to better understand immediate and long-term side effects of these agents. The results of this literature review uncovered a number of potential side effects, some of which are acknowledged and many of which are not noted in the prescribing information for these agents. Among the unacknowledged side effects are: an increased risk of HIV transmission for depot medroxyprogesterone acetate (DMPA), and for combination contraceptives breast cancer, cervical cancer, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, depression, mood disorders and suicides (especially among women twenty-five years of age and younger, in the first six months of use), multiple sclerosis, interstitial cystitis, female sexual dysfunction, osteoporotic bone fractures (especially for progesterone-only contraceptives), and fatty weight gain. Misleading prescribing information regarding cardiovascular and thrombotic risks are also noted. Women seeking birth control have a right to be informed and educated about risk avoidance through the use of effective nonhormonal methods like fertility awareness methods. In one case-that of DMPA-the increased risk of HIV acquisition has been conclusively demonstrated to be both real and unique to this drug. Considering the availability of numerous alternatives, there is no justification for the continued marketing of DMPA to the public. We reviewed the effect of hormonal contraceptives on women's health. A number of potential side effects were noted including increased risks of breast cancer, cervical cancer, inflammatory bowel disease, lupus, multiple sclerosis, cystitis, bone fractures, depression, mood disorders and suicides, fatty weight gain, and female sexual dysfunction. With the long-acting injectable contraceptives there is an increased risk of getting HIV. Misleading prescribing information regarding the risks of heart attacks, strokes and blood clotting problems were also noted. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free Fertility Awareness Methods.
Traven SA et al., 2021 Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
To use the Truven MarketScan database to (1) report the incidence of venous thromboembolism (VTE), including deep vein thromboses (DVTs) and pulmonary embolism (PE), in patients undergoing simple knee arthroscopy and anterior cruciate ligament (ACL) reconstruction, and (2) evaluate combined oral contraceptive (COCP) use as a potential risk factor for VTE in patients undergoing knee arthroscopy. All female patients between the ages of 16 and 40 years undergoing knee arthroscopy and ACL reconstruction between 2010 and 2015 were identified in the MarketScan database. Patients were stratified by whether they had a documented pharmaceutical claim for COCP therapy, and the primary outcome was the risk of DVT and or PE within 90 postoperative days. In total, 64,165 patients were identified for inclusion. While the overall incidence of VTE was low, patients taking COCPs had an increased risk of a DVT or PE compared with those not on COCPs (odds ratio [OR] 2.1, P < .001). When patients were analyzed by procedural subgroup (ACL reconstruction and simple knee arthroscopy), similar results held true. Furthermore, smoking and obesity had a synergistic effect when combined with COCPs use on the risk of VTE. Specifically, 3.1% of patients with obesity on COCPs (OR 3.1, P < .001) and 4.0% of smokers on COCPs (OR 4.3, P < .001) developed a postoperative VTE. This study demonstrates that COCP use is associated with an increased risk for a symptomatic DVT or PE (1.70% and 0.27%, respectively) after knee arthroscopy and an increased risk for DVT, but not PE (1.80% and 0.23%, respectively), after ACL reconstruction. In addition, patients with multiple risk factors present such as tobacco use, obesity, and COCP use had odds ratios greater than the sum of the individual risk factors alone. level III prognostic cohort study.
Fehring RJ et al., 2021 Linacre Q
Marital chastity is the practice of periodic abstinence with use of natural family planning (NFP). The purpose of this study was to determine the influence of the most common methods of contraception (female sterilization, oral contraceptive pills, and condoms) and NFP on divorce/separation and cohabitation rates among reproductive age women. The study involved an extensive review of the literature on the effects of practice of NFP on marital dynamics and a statistical analysis of 2,550 ever-married women in the (2015-2017) National Survey of Family Growth data set. Importance of religion and frequency of church attendance were included in the analysis. With ever-use of NFP, 14 percent were divorced or separated, and 27 percent to 39 percent were divorced or separated with ever-use of oral contraceptive pills. Stepwise logistic regression indicated that ever-use of contraception was associated with increased odds of divorce or separation (odds ratio [OR] = 2.05; confidence interval [CI]: 1.96-2.49) and cohabitation (2.95, CI: 2.20-3.95). Ever-use of NFP yielded 58 percent lower odds for divorce or separation. Frequent church attendance was associated with lower odds of divorce or separation and cohabitation. Although there are lower odds of divorce among NFP users, the reason might be due to their religiosity. This study showed that ever-use of natural family planning (NFP) among ever-married women was associated with 58 percent lower odds of divorce than among women who never-used NFP. Ever-use of contraceptive methods was associated with two times the odds of divorce and four times for cohabitation compared to those women who never-used those methods. Use of periodic abstinence with NFP is the practice of marital chastity and is thought to strengthen the marital relationship.
Singata-Madliki M et al., 2021 Int J Gynaecol Obstet Open Access
To compare the effects of depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and copper intrauterine device (IUD) on mood and sexual function. At the Effective Care Research Unit in South Africa, women already randomized in the ECHO Trial to the three methods were asked to participate in this study. Participants were interviewed at 3 and 12 months after enrollment using the Beck Depression Inventory and Arizona Sexual Experiences Scale, and at 12 months using the WHO-5 Wellbeing Index and the Patient Global Impression scale. A total of 605 women participated. There was little difference in depression at 3 months across the three study groups. Contrary to our hypothesis, at 12 months, depression was lowest among DMPA-IM users (16/167, 9.6%) and highest among IUD users (28/158, 17.7%) (p = 0.032). There was little difference in sexual function at any time-point. More women in the DMPA-IM group felt "very much better" on the PGI scale than in the IUD and LNG implant groups (p = 0.003). Depression may be less likely with DMPA-IM than with the other methods 1 year after initiation. Major differences in sexual functioning are unlikely. Unhappiness related to not using DMPA-IM, the most popular method in our setting, may have skewed results. PACTR201706001651380.
Mosorin ME et al., 2020 Eur J Endocrinol
The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial. The study is a prospective longitudinal population-based cohort study. The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n = 153), progestin-only contraceptive (POC, n = 842), and non-hormonal contraceptive users (n = 884). In the entire study population, current CHC use was significantly associated with prediabetes (OR: 2.0, 95% CI: 1.3-3.2) and type 2 diabetes (OR: 3.3, 95% CI: 1.1-9.7) compared to non-hormonal contraceptive use. After 5 years of use, the prediabetes risk increased 2.2-fold (95% CI: 1.3-3.7) and type 2 diabetes risk increased 4.5-fold (95% CI: 1.5-13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR: 1.9, 95% CI: 1.2-3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for BMI and socioeconomic status. CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.
Bronnick MK et al., 2020 Frontiers in Psychology Open Access
Hormonal contraceptive drugs are being used by adult and adolescent women all over the world. Convergent evidence from animal research indicates that contraceptive substances can alter both structure and function of the brain, yet such effects are not part of the public discourse or clinical decision-making concerning these drugs. We thus conducted a systematic review of the neuroimaging literature to assess the current evidence of hormonal contraceptive influence on the human brain. The review was registered in PROSPERO and conducted in accordance with the PRISMA criteria for systematic reviews. Structural and functional neuroimaging studies concerning the use of hormonal contraceptives, indexed in Embase, PubMed and/or PsycINFO until February 2020 were included, following a comprehensive and systematic search based on predetermined selection criteria. A total of 33 articles met the inclusion criteria. Ten of these were structural studies, while 23 were functional investigations. Only one study investigated effects on an adolescent sample. The quality of the articles varied as many had methodological challenges as well as partially unfounded theoretical claims. However, most of the included neuroimaging studies found functional and/or structural brain changes associated with the use of hormonal contraceptives. The included studies identified structural and functional changes in areas involved in affective and cognitive processing, such as the amygdala, hippocampus, prefrontal cortex and cingulate gyrus. However, only one study reported primary research on a purely adolescent sample. Thus, there is a need for further investigation of the implications of these findings, especially with regard to adolescent girls.
Edwards AC et al., 2020 Psychol Med Open Access
Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.
Buskmiller C et al., 2020 Linacre Q
This review sought to evaluate the evidence for embryo formation during intrauterine device (IUD) use, to articulate how often embryo loss occurs in well-designed studies, and to comment on other bodies of literature suggestive of postfertilization mechanisms of action of IUDs. The MEDLINE, EMBASE, and Ovid databases were searched for English-language studies of markers of pregnancy in IUD users in May 2018. Studies of human chorionic gonadotropin (hCG) were subjected to quality assessment based on the US Preventive Services Task Force quality tool. Bias of studies assessing pregnancy in other ways was assessed on a study-to-study basis. In all, 1,073 studies were identified and 138 were read in detail. Twenty-three studies of β-hCG, 4 studies of direct observation of embryos in fallopian tubes, 2 studies of pregnancy-specific binding globulin (PSBG), and 1 study of heat-shock protein 10 (Hsp10) or chaperonin 10 were included. In all studies considered together, 7.3 percent of IUD users had evidence of fertilization and pregnancy failure. In good-quality studies, 4.5 percent had evidence of fertilization and pregnancy failure. There are no randomized trials of embryo formation and loss in IUD users compared with noncontracepting controls. Studies of β-hCG span a large spectrum of quality, but several good-quality studies exist, which support embryo formation and loss in IUD users. Evidence of embryos found in tubes is moderate and evidence of PSBG and Hsp10 elaboration was limited, but these are also concerning for embryo formation and loss. There is good-quality evidence of embryo formation and loss in IUD users. Studies are inconsistent, and the stated conclusions of several papers inaccurately diminish postfertilization evidence of embryo formation. To better assess the rate of embryo loss in IUD users compared with non-users, future research should include well-designed prospective trials and less subjective assessments of embryos in fallopian tubes. A systematic review was carried out examining the English-language literature in the MEDLINE, EMBASE, and Ovid databases for evidence of embryo formation and loss during IUD use. In all, 1,073 studies were identified and 138 were read. There are no randomized trials and evidence ranges in quality, but evidence for the embryo formation and loss in 4.5 percent of IUD users exists in good-quality research. Further research is needed to compare embryo loss in IUD users to loss in controls.
Garforth B et al., 2020 Sci Rep Open Access
Oral contraception (OC) is used by approximately fifty-five million women in the USA alone and is listed as an essential medicine by the World Health Organisation. Altered mood is a common reason for OC cessation. Here we investigate the effects of OC on hormones that are linked to mood. We obtained blood samples from 185 young women (average age 21.2) in two cohorts and tested the effects of OC on plasma levels of oxytocin, adrenocorticotropic hormone (ACTH), estradiol, progesterone and testosterone. We related plasma hormone levels with self-reported measures of mood, well-being and depression. OC-users in both cohorts showed elevated basal oxytocin, lower ACTH, estradiol, progesterone and testosterone compared with non-OC users. Satisfaction With Life Score (SWLS) was higher in OC -users compared to non-OC users, with no differences in the Beck Depression Score (BDI) and Positive And Negative Affect Schedule (PANES). In conclusion, our data show alterations in hormone levels and SWLS in response to OC.
Hapgood JP, 2020 AIDS research and human retroviruses
Intramuscular depo-medroxyprogesterone acetate (DMPA-IM) is the most widely used hormonal contraceptive in sub-Saharan Africa. Previous meta-analyses of observational studies found a significant 40%-50% increased risk associated with DMPA-IM use, relative to no contraception or infrequent condom use. This raised substantial concerns, although these studies had important limitations. Consequently, the open-label randomized Evidence for Contraceptive Options and HIV Outcomes trial was conducted, designed primarily to detect a 50% or greater difference in HIV risk between DMPA-IM, the levonorgestrel (LNG) implant, and the copper-intrauterine device. The ECHO study, published in July 2019, concluded that there is no substantial difference in HIV risk among the methods evaluated, and that all three methods are safe and highly effective. In response, the WHO relaxed the Medical Eligibility Criteria for DMPA-IM use among women at high HIV risk in August 2019. However, two of the three comparisons in the ECHO trial could rule out neither a 50% increase nor no change in HIV risk for one contraceptive compared with another. The study had limitations and the results contained considerable uncertainty. They also did not inform on associated HIV risk for any one of the individual methods due to the absence of a control group such as no contraception or only infrequent condom use. The HIV risks associated with LNG implant and copper-IUD relative to no contraception or infrequent condom use are unknown and these cannot be seen as controls, nor did the authors claim them to be. The results will be discussed in the context of their limitations, what they add to the body of work to date on contraception and HIV acquisition, and the implications of the findings and reports thereof for future research and contraceptive choice.
Iyanda AE et al., 2020 Int J Public Health Open Access
We examined the association between incorrect knowledge of ovulation and unintentional pregnancy and child among young women in sub-Saharan Africa countries. Using Pearson's Chi-square, t test, multiple logistic regression, and likelihood ratio test, we analyzed Demographic and Health Survey data (2008-2017) of 169,939 young women (15-24 year). The range of prevalence of incorrect knowledge of ovulation was 51% in Comoros and 89.6% in Sao Tome and Principe, while unintentional pregnancy ranged between 9.4% in the Republic of Benin and 59.6% in Namibia. The multivariate result indicates a strong association between incorrect knowledge of ovulation and unintentional pregnancy (OR = 1.17; p < 0.05) and unintentional child (OR = 1.15; p < 0.05). Adolescent women (15-19) generally have poor knowledge of ovulation and are more likely to report an unintentional pregnancy/child than women between ages 20-24. To reduce the burden of unintentional child/pregnancy in Africa, fertility knowledge should not only be improved on but must consider the sociocultural context of women in different countries that might affect the adoption of such intervention programs. Pragmatic efforts, such as building community support for young women to discuss and share their experiences with professionals and educate them on fertility and sexuality, are essential.
Webb S et al., 2020 Women's Health Reports Open Access
To understand how Title X providers currently engage with fertility awareness-based methods (FABMs) for pregnancy prevention in Title X clinics across the United States. We developed a survey to assess knowledge of fertility for purposes of pregnancy prevention, attitudes toward FABMs use for pregnancy prevention, and practices when patients request FABMs for pregnancy prevention. In total, 329 participants who met all inclusion criteria completed the survey. Respondents were generally highly knowledgeable on fertility, felt neutrally toward FABMs or thought they were a nonviable option for most women, and were likely to respond to patient requests for FABMs for pregnancy prevention by providing information. Qualitative responses included several barriers to provision of FABMs for pregnancy prevention and few successes to provision. Fertility knowledge and discussion of specific methods increased with the number of methods included in the clinic's written materials or with the number of different FABMs someone at that clinic had been trained on. Significant clinician or administrative barriers may exist to offering FABMs to patients. Incorporating up-to-date information on a range of FABMs-rather than treating them as one method-into contraceptive counseling represents an opportunity to increase the contraceptive offering for clients who want them, leading to increased patient satisfaction and successful family planning outcomes.
Dinehart E et al., 2020 Journal of assisted reproduction and genetics Open Access
Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.
Larsen B et al., 2020 Frontiers in physiology
This study investigated the association between synthetic ovarian hormone use [i.e., the oral contraceptive (OC) pill] and basal C-reactive protein (CRP), peripheral blood immune cell subsets, and circulating pro- and anti-inflammatory cytokine concentrations in elite female athletes. Elite female athletes (n = 53) selected in Rio Summer Olympic squads participated in this study; 25 were taking an OC (AthletesOC) and 28 were naturally hormonally cycling (AthletesNC). Venous blood samples were collected at rest for the determination of sex hormones, cortisol, CRP, peripheral blood mononuclear memory and naïve CD4+ T-cells, CD8+ T-cells and natural killer cells, as well as pro- and anti-inflammatory cytokine concentrations. C-reactive protein concentrations were elevated (p < 0.001) in AthletesOC (median = 2.02, IQR = 3.15) compared to AthletesNC (median = 0.57, IQR = 1.07). No differences were reported for cortisol, cytokines, or PBMC immune cell subsets, although there was a trend (p = 0.062) for higher IL-6 concentrations in AthletesNC. Female Olympians had substantially higher CRP concentrations, a marker of inflammation and tissue damage, before the Rio Olympic Games if they used an OC. Future research should examine the potential consequences for athlete performance/recovery so that, if necessary, practitioners can implement prevention programs.
Shaaban YM et al., 2019 BMC ophthalmology
To evaluate the effect of oral contraceptive pills (OCP) on the macula, the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the choroidal thickness (CT). In this prospective observational cross-sectional study, 60 eyes of 30 healthy women taking monophasic OCP (0.03 mg ethinylestradiol and 0.15 mg levonorgestrel) for contraception for at least 1 year were compared with 60 eyes of a control group of 30 healthy women who were not taking any OCP. Spectral-Domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macula, the RNFL, the GCL, and the CT. Measurements were taken in the follicular phase (day 3) of the last menstrual cycle in all women. The body mass index (BMI) scores of all participants were also recorded. No disparity in terms of age and BMI between both groups was observed (p = 0.444, p = 0.074, respectively). All the macular parameters measurements were considerably lower in the OCP group compared to the control group (p < 0.001). Also, the RNFL thickness, the GCL thickness, and the CT were all significantly thinner in the OCP group (p < 0.001). The use of OCP can cause significant changes in the retina and choroid thickness over 1 year period. The women who are using OCP for a longer duration could have some eye problems. OCT should be routinely done for follow up. Further long term studies are required, using different preparations of OCP. It is important to find out when this thickness alterations can be clinically significant or symptomatic and if these changes are reversible or not.
de Wit AE et al., 2019 JAMA Psychiatry Open Access
Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear. To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use. DESIGN, SETTING, Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019. Exposure: Oral contraceptive use at 16, 19, 22, and 25 years of age. Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years). Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs -0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age, -0.021; 95% CI, -0.038 to -0.005; P = .0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P < .001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P = .006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P = .009) than nonusers. Conclusions and Relevance: Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence.
Anderl C et al., 2019 J Child Psychol Psychiatry Open Access
Previous evidence suggests that use of oral contraceptives (OCs), especially during adolescence, may increase women's vulnerability to depression in the short term. Here, we investigate whether women who had first used OC in adolescence show an increased prevalence of depression in the long term. We examined 1,236 women in the United States National Health and Nutrition Examination Survey for whom information on depression and age at first OC use was publicly available. We compared women who reported first use of OCs in adolescence to women who had never used OCs and women who had first used OCs in adulthood on 1-year prevalence of major depressive disorder (MDD) assessed by trained interviewers. Compared with women who had used OCs during adolescence, women who had never used OCs were less likely to meet the criteria for MDD within the past year in adulthood [odds ratio (OR) = 0.31, 95% CI = 0.16-0.60], and so were women who only started using OCs in adulthood (OR = 0.54, 95% CI = 0.30-0.95). Third factors that have previously been proposed to explain the relationship between OC use and depression risk such as age at sexual debut, and, importantly, current OC use, did not account for the results in propensity score analyses. We show a long-term association between adolescent OC use and depression risk in adulthood regardless of current OC use. Our findings suggest that adolescence may be a sensitive period during which OC use could increase women's risk for depression, years after first exposure.
Pletzer B et al., 2019 Sci Rep Open Access
Oral contraceptive (OC) effects on the brain have gained increasing interest, but are highly controversial. Previous studies suggest that OC users have larger hippocampi, parahippocampi, fusiform gyri and Cerebelli. Preliminary evidence from one of those studies even suggests an effect of previous contraceptive use on the hippocampi of women who are not current users of OCs. Furthermore, more recent studies postulate an involvement of previous OC treatment in later development of mood disorders. To address the question whether previous OC treatment affects women's brain structure later in life, high resolution structural images were obtained from 131 naturally cycling women. Among them, 52 women had never used OC before, 52 had previously used one OC for a continuous time period and 27 had previously used multiple contraceptives. The groups did not differ in gray matter volumes. Since endogenous sex hormones modulate gray matter volumes of the hippocampus and basal ganglia along the menstrual cycle, we hypothesize effects of OC use on these areas. Specifically, we hypothesize that a longer duration of previous OC treatment is related to larger hippocampi and larger basal ganglia. Indeed we found the duration of previous OC use to be positively correlated to hippocampal and basal ganglia volumes bilaterally. For the hippocampus, but not for the basal ganglia, this association disappeared after controlling for the time since discontinuation. These results suggest that for the hippocampus, but not for the basal ganglia, effects of previous contraceptive treatment are reversed after a time period comparable to treatment duration. These data question the immediate reversibility of OC effects on brain structure. Accordingly, some changes in the brain due to long-term contraceptive use, while subtle, may be long-lasting.
Berglund Scherwitzl E et al., 2019 Eur J Contracept Reprod Health Care Open Access
The aim of the study was to compare the effect of previously used contraceptive methods on women's shortand long-term fecundity. Use of hormonal contraception (HC) was compared with the use of a contraceptive mobile application (app). This real-life prospective observational study comprised 2874 women who were attempting to become pregnant using the Natural Cycles mobile app to monitor their fertility. The women registered to use the app between August 2014 and June 2016 with the intention of planning a pregnancy and had previously either used the same app to prevent pregnancy or had recently discontinued HC use. We calculated the average time to pregnancy (TTP) for all women who became pregnant during the study and performed Kaplan-Meier life-table analysis to examine the cumulative probabilities of pregnancy for all women in the study. The average TTP was 2.3 (95% confidence interval [CI] 2.1, 2.4) and 3.7 (95% CI 3.4, 3.9) cycles for women who had previously used Natural Cycles and HC, respectively. The time to reach 30% pregnancy probability for women previously on HC was 1.6 (95% CI 1.5, 1.8) times longer than for women previously using Natural Cycles. There was no significant difference in the 13 cycle cumulated pregnancy probability between the two groups. The results show that fertility awareness-based methods of contraception increase short-term pregnancy rates relative to HC, but have no effect on long-term pregnancy rates.
Ibrahim H et al., 2019 Journal of Taibah University Medical Sciences
Weight gain remains an issue for contraceptive users due to the high prevalence of obesity. This retrospective study compares the weight gain between hormonal and non-hormonal contraceptive users in government health clinics in Kota Bharu, Kelantan, Malaysia. A total of 380 women who had used the same contraceptive method for at least twelve months were recruited in this study. Covariance analysis was done to compare the weight gain between hormonal and non-hormonal contraceptive users, while studying the same confounders [age, household income, number of pregnancies, and baseline body mass index (BMI)]. Hormonal methods were more commonly used. The mean weight gain among hormonal users (adjusted mean 2.85, 95% CI 2.45, 3.24) was significantly higher than non-hormonal users (adjusted mean 0.46, 95% CI -0.73, 1.65; p-value <0.001), after controlling for age, household income, number of pregnancies, and baseline BMI. The possibility of weight gain following the use of hormonal methods should be investigated and non-hormonal methods should be considered to prevent weight gain. أهداف البحث: لا تزال زيادة الوزن قضية، لمستخدمات وسائل منع الحمل بسبب زيادة الوزن وانتشار معدل السمنة. تهدف هذه الدراسة المرجعية لمقارنة زيادة الوزن بين موانع الحمل الهرمونية وغير الهرمونية في عيادات الصحة الحكومية في مدينة بهارو، كلنتان، ماليزيا. طرق البحث: تم مشاركة ما مجموعه ٣٨٠ سيدة من اللواتي استخدمن نفس وسيلة منع الحمل لمدة ١٢ شهرا في هذه الدراسة. تم عمل تحليل التباين لمقارنة زيادة الوزن بين مستخدمات موانع الحمل الهرمونية وغير الهرمونية، أثناء دراسة نفس العوامل (العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي). النتائج: كانت الطرق الهرمونية هي الأكثر شيوعا. متوسط زيادة الوزن بين مستخدمات الهرمون (المتوسط المعدل ٢.٨، فاصل الثقة ٩٥٪ ٢.٤٥، ٣.٢٤) أعلى بكثير من مستخدمات الطرق غير الهرمونية (المتوسط المعدل ٠.٤٦، فاصل الثقة ٠.٧٣-، ١.٦٥) بعد التحكم في العمر، ودخل الأسرة، وعدد مرات الحمل ومؤشر كتلة الجسم الأساسي. الاستنتاجات: ينبغي التحقق من إمكانية زيادة الوزن بعد استخدام الطرق الهرمونية وينبغي النظر في خيارات أخرى من الطرق غير الهرمونية للحد من زيادة الوزن.
McKetta S et al., 2019 Ann Epidemiol Open Access
Depression is a prevalent health problem affecting U.S. women. Oral contraceptive pills (OCPs) are commonly used for pregnancy prevention, and evidence is mixed regarding any increased risk for incident depression among users, particularly adolescents. We examined the relationship between OCP use and depressive disorders among female adolescents using validated, structured interview assessments in a general population sample of adolescents in the National Comorbidity Survey-Adolescent Supplement. Respondents were 4765 female adolescents with no history of pregnancy who reported current OCP use, lifetime OCP use, and age of OCP initiation. Lifetime and current depressive disorders, including major depressive disorder and depressive episodes, were assessed by lay interviewers. In logistic regression models adjusted for a range of confounders, there was no relationship between ever using OCPs and lifetime depressive disorder (OR 1.10, 95% CI 0.88-1.37), nor current use of OCPs and current depressive disorder (OR 0.82, 95% CI 0.50-1.35). Using survival analysis for age-of-onset data, we found that OCP use is not associated with an increased risk of depressive disorders. In sum, use of OCPs in a general population sample of adolescents did not increase the risk of depressive disorders.
Jung SJ et al., 2018 J Affect Disord
The association of suicide with the use of oral contraceptives (OC) is unknown in the Asian population. We aimed to evaluate the association of OC use and suicidal behavior in a nationally representative population of Korean women. Of the 44,501 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20 years or older who had completed information on OC use and suicidal behavior were included. Women with a history of cancer were excluded. Compared to non-users of OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a multivariable logistic regression among OC users, with testing of the interaction term of OC use and history of depression. We also conducted a stratified analysis by history of depression. A total of 4,067 women (14.0%) reported they had suicide ideations or had attempted suicide, respectively. OC use was associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00-1.24) after adjustments for age, demographic factors, age of menarche, and lifestyle behaviors. When stratified by history of depression diagnosis, ORs linearly increased as the total duration of OC use lengthened among women with a history of depression; however, women without a history of depression showed peaked OR at 4to 12-month use. There is an increased association between OC use and suicidality and the pattern of the relationship differs depending on whether there is a history of depression.
Fehring RJ et al., 2018 Linacre Q Open Access
Oral contraceptives (OCs) are often prescribed to adolescents and young adults for the treatment of health problems and to avoid unwanted pregnancies. We hypothesized that the use of OCs, among adolescents and young adults, is associated with a greater likelihood of pregnancy, abortion, sexually transmitted diseases (STDs), pelvic inflammatory disease (PID), and sexual behaviors that will enhance those problems (i.e., earlier sexual debut and more sexual partners) than adolescents and young adults not using OCs. To test this hypothesis, data from 1,365 adolescents and young adults in the 2011-2013 National Survey of Family Growth (NSFG) were used to describe the influence of ever use of OCs on ever having sex, sexual debut, multiple sexual partners, STDs, PID, pregnancy, and abortion. A secondary purpose was to evaluate protective factors from unhealthy sexual practices like religiosity, church attendance, and intact families. We found that the "ever use" of OCs by US adolescents and young adults results in a greater likelihood of ever having sex, STDs, PID, pregnancy, and abortion compared with those adolescents and young adults who never used OCs. Furthermore, those adolescents who ever used OCs had significantly more male sexual partners than those who never used OCs, and they also had an earlier sexual debut by almost two years. Conversely, we found that frequent church attendance, identification of the importance of religion, and having an intact family among adolescents were associated with less likelihood of unsafe sexual practices. We concluded that the use of OCs by adolescents and young adults might be considered a health risk. Further research is recommended to confirm these associations. The purpose of this article was to show the correlation between contraceptive use in adolescents and negative sexual outcomes. We used data from the 2011-2013 NSFG and demonstrated that never married adolescents who used oral hormonal contraception were three times more likely to have an STD, have PID, and to become pregnant, and, surprisingly, ten times more likely of having an abortion compared to noncontracepting adolescents. These are outcomes that contraception is intended to prevent. These data also showed that the contraceptors had significantly more male partners than their contraceptive counterparts. Protective factors such as church attendance and family cohesiveness were associated with a decreased likelihood of sexual activity.
Maritz MF et al., 2018 PLoS One Open Access
High usage of progestin-only injectable contraceptives, which include the intramuscular injectables depo-medroxyprogesterone acetate (DMPA-IM, Depo-Provera) and norethisterone (NET) enanthate (NET-EN or Nur-Isterate), correlates worldwide with areas of high HIV-1 prevalence. Epidemiological data show a significant association between usage of DMPA-IM and increased HIV-1 acquisition but no such association from limited data for NET-EN. Whether MPA and NET have similar effects on HIV-1 acquisition and pathogenesis, and the relationship between these effects and the dose of MPA, are critical issues for women's health and access to suitable and safe contraceptives. We show for the first time that MPA, unlike NET, significantly increases HIV-1 replication in peripheral blood mononuclear cells (PBMCs) and a cervical cell line model. The results provide novel evidence for a biological mechanism whereby MPA, acting via the glucocorticoid receptor (GR), increases HIV-1 replication by at least in part increasing expression of the CCR5 HIV-1 coreceptor on target T-lymphocytes. MPA, unlike NET, also increases activation of T-cells and increases the CD4/CD8 ratio, suggesting that multiple mechanisms are involved in the MPA response. Our data offer strong support for different biological mechanisms for MPA versus NET, due to their differential GR activity. The dose-dependence of the MPA response suggests that significant effects are observed within the range of peak serum levels of progestins in DMPA-IM but not NET-EN users. Dose-response results further suggest that effects of contraceptives containing MPA on HIV-1 acquisition and disease progression may be critically dependent on dose, time after injection and intrinsic factors that affect serum concentrations in women.
Worly BL et al., 2018 Contraception
We performed a systematic review to look for an association between progestin-only contraception and depression. We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders. We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression. Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).
Kavanaugh ML et al., 2018 Contraception
The objective was to examine levels of, correlates of and changes in the use of individual and grouped methods of contraception among US females aged 15-44 from 2008 to 2014. Using three rounds of the National Survey of Family Growth, we analyzed samples of 12,279 (2008), 5601 (2012) and 5699 (2014) females. We conducted simple and multivariable logistic regression analyses to identify associations between demographic characteristics and contraceptive use, as well as between characteristics and changes in use patterns. In terms of overall trends in contraceptive use between 2008 and 2014, there was no significant change in the proportion of women who used a method among either all women (60%) or those at risk of unintended pregnancy (90%). Significant changes in use occurred among six methods. The largest increase in use was among users of long-acting reversible contraceptive (LARC) methods, including the intrauterine device and implant - from 6% to 14% - across almost all population groups of female contraceptive users, while the largest decrease occurred among users of sterilization - from 37% to 28% - with lower-income women driving the decline in female sterilization and higher-income women driving the decline in a partner's sterilization as a primary method. Moderate increases were seen in the use of withdrawal and natural family planning. Most shifts in recent contraceptive use have occurred among the most effective methods - sterilization and LARCs. Differences in method-specific user characteristics underscore the importance of ensuring full access to the broad range of methods available. The lack of change in the overall use of contraceptives among women at risk for unintended pregnancy may have implications for the extent to which further declines in national rates of unintended pregnancy can be expected.
Skovlund CW et al., 2017 Am J Psychiatry
The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception. Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85–2.10) for suicide attempt and 3.08 (95% CI=1.34–7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79–2.03) for oral combined products, 2.29 (95% CI=1.77–2.95) for oral progestin-only products, 2.58 (95% CI=2.06–3.22) for vaginal ring, and 3.28 (95% CI=2.08–5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use. Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.
Dumitru AM et al., 2017 Issues Law Med
Background and PurposePublished reports indicate that over 100 million women worldwide use the birth control pill (Oral Contraceptives, or OCPs).1,2 However, in a national study conducted by the Battelle Centers for Public Health Research and Evaluation, rates of discontinuation of some birth control methods were as high as 90%, and had averages between 40-61% (depending on marital status) for women who were followed over a two-year period.3 This suggests that women are searching for new methods, perhaps with fewer side effects or better effectiveness rates. Studies show up to 60% of women would be interested in using Fertility Awareness Based Methods (FABMs) if given information.4 Both FABMs and OCPs entail behavior modification on a daily basis, so the efficacy and side effects of FABMs and OCPs were chosen for comparison during this study.Most commonly reported unintended pregnancy rates for FABMs and OCPs are based on low quality retrospective surveys. A popularly cited review from J. R. Trussell and colleagues reports typical use failure rates of 24% for FABMs and 9% for OCPs.5 These numbers are based on estimates of the probability of pregnancy drawn from the 1995 and 2002 National Surveys of Family Growth.5'6 There are at least three major problems with these surveys. One is that these are lower quality retrospective surveys based primarily on patient recall, with the data collected via a series of phone surveys. Another major problem is that 86% of the purported FABM users surveyed identified the calendar method-a much older and less effective method-as their primary form of contraception. Then, the rates for all types of FABMs were pooled together, including some methods which are not even classified as FABMs by trained providers. This lumping together of all FABMs including rhythm masks important differences in effectiveness among the variety of modern methods; a fact acknowledged by Trussell, the author of this estimate.7'8'9 The third major issue with this review is that the rates of effectiveness were adjusted to account for the researchers' assumption of underreporting of abortion. As a result of the issues with these popularly cited statistics, we sought to design objective criteria with which to evaluate the primary literature available for FABMs and OCPs, in order to understand both the quality of the studies available as well as the true effectiveness rates. In total, three major search engines (Medline, PubMed, and EMBASE) were used with keyword searches to identify relevant articles. For FABMs, 30 articles from 1980 on were included in the study.6 For OCPs, 47 articles from 2000 on were included in the study. (The year 2000 was chosen in part because studies from earlier decades had used higher dose hormone formulations which were proven to be unsafe for women, and the trend in later years has been towards seeking lower dose hormonal formulations to provide the same efficacy with fewer side effects1). Strength of Recommendation Taxonomy (SORT) criteria10 were established first for the FABM review6 and then adapted for the OCP review (Adapted SORT). The adaptation was based on fundamental differences between FABMs and OCPs such as lack of a learning phase for OCPs. The purpose of the SORT and Adapted SORT criteria was to provide a framework to determine the level of evidence for individual studies.Two independent reviewers scored each of the identified articles for the FABMs and the OCPs reviewed. Major discrepancies in scores were resolved by sending the articles in question to a third reviewer for a tie-break score. For the FABMs reviewed, there were 56 maximum possible points with the SORT criteria. The scores ranged from 31-55 points, and 10 of the 30 articles (30%) were found to earn a SORT Level 1 status (qualified by earning a positive score in all of the critical criteria).6For the OCPs reviewed, there were 42 maximum possible points with the Adapted SORT criteria. …
Unseld M et al., 2017 Front Public Health Open Access
Birth control is a persistent global health concern. Natural family planning (NFP) comprises methods to achieve or avoid pregnancy independent of mechanical or pharmacological intervention. The sympto-thermal method (STM) of NFP employs daily observation of cervical fluids and measurement of basal body temperature. This multi-country study was undertaken to describe the characteristics of STM users, understand their perceptions of NFP, and its perceived impact on relationships. Questionnaires for women and men were developed in German and translated to English, Polish, Italian, Czech, and Slovak by native speakers. A total of 2,560 respondents completed the online questionnaire (37.4% response). Participants were married (89%) and well educated, and their self-perceived financial status was described as "good" or "very good" by 65% of the respondents. Forty-seven percent had previously used contraceptives. Ninety-five percent of women and 55% of men said using NFP has helped them to know their body better. Large majorities of men (74%) and women (64%) felt NFP helped to improve their relationship while <10% felt use of NFP had harmed their relationship. Most women (53%) and men (63%) felt using NFP improved their sex life while 32% of women and 24% of men felt it was unchanged from before they used NFP. Seventy-five percent of women and 73% of men said they are either "satisfied" or "very satisfied" with their frequency of sexual intercourse. This survey demonstrates STM of NFP is a well-accepted approach to family planning across several Western cultures. It is consistently viewed as being beneficial to couples' self-knowledge, their relationship, and satisfaction with frequency of sexual intercourse.
Sundaram A et al., 2017 Perspect Sex Reprod Health Open Access
Contraceptive failure rates measure a woman's probability of becoming pregnant while using a contraceptive. Information about these rates enables couples to make informed contraceptive choices. Failure rates were last estimated for 2002, and social and economic changes that have occurred since then necessitate a reestimation. To estimate failure rates for the most commonly used reversible methods in the United States, data from the 2006-2010 National Survey of Family Growth were used; some 15,728 contraceptive use intervals, contributed by 6,683 women, were analyzed. Data from the Guttmacher Institute's 2008 Abortion Patient Survey were used to adjust for abortion underreporting. Kaplan-Meier methods were used to estimate the associated single-decrement probability of failure by duration of use. Failure rates were compared with those from 1995 and 2002. Long-acting reversible contraceptives (the IUD and the implant) had the lowest failure rates of all methods (1%), while condoms and withdrawal carried the highest probabilities of failure (13% and 20%, respectively). However, the failure rate for the condom had declined significantly since 1995 (from 18%), as had the failure rate for all hormonal methods combined (from 8% to 6%). The failure rate for all reversible methods combined declined from 12% in 2002 to 10% in 2006-2010. These broad-based declines in failure rates reverse a long-term pattern of minimal change. Future research should explore what lies behind these trends, as well as possibilities for further improvements.
Skovlund CW et al., 2016 JAMA Psychiatry
Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. DESIGN, SETTING, This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016. Exposures: Use of different types of hormonal contraception. Main Outcomes and Measures: With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital. A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.
Lopez LM et al., 2016 Cochrane Database Syst Rev Open Access
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users. The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight. Until 4 August 2016, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. For the initial review, we contacted investigators to identify other trials. Selection Criteria: We considered comparative studies that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight. Data Collection and Analysis: Two authors extracted the data. Non-randomized studies (NRS) need to control for confounding factors. We used adjusted measures for the primary effects in NRS or the results of matched analysis from paired samples. If the report did not provide adjusted measures for the primary analysis, we used unadjusted outcomes. For RCTs and NRS without adjusted measures, we computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% CI. MAIN We found 22 eligible studies that included a total of 11,450 women. With 6 NRS added to this update, the review includes 17 NRS and 5 RCTs. By contraceptive method, the review has 16 studies of depot medroxyprogesterone acetate (DMPA), 4 of levonorgestrel-releasing intrauterine contraception (LNG-IUC), 5 for implants, and 2 for progestin-only pills.Comparison groups did not differ significantly for weight change or other body composition measure in 15 studies. Five studies with moderate or low quality evidence showed differences between study arms. Two studies of a six-rod implant also indicated some differences, but the evidence was low quality.Three studies showed differences for DMPA users compared with women not using a hormonal method. In a retrospective study, weight gain (kg) was greater for DMPA versus copper (Cu) IUC in years one (MD 2.28, 95% CI 1.79 to 2.77), two (MD 2.71, 95% CI 2.12 to 3.30), and three (MD 3.17, 95% CI 2.51 to 3.83). A prospective study showed adolescents using DMPA had a greater increase in body fat (%) compared with a group not using a hormonal method (MD 11.00, 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD -4.00, 95% CI -6.93 to -1.07). A more recent retrospective study reported greater mean increases with use of DMPA versus Cu IUC for weight (kg) at years 1 (1.3 vs 0.2), 4 (3.5 vs 1.9), and 10 (6.6 vs 4.9).Two studies reported a greater mean increase in body fat mass (%) for POC users versus women not using a hormonal method. The method was LNG-IUC in two studies (reported means 2.5 versus -1.3; P = 0.029); (MD 1.60, 95% CI 0.45 to 2.75). One also studied a desogestrel-containing pill (MD 3.30, 95% CI 2.08 to 4.52). Both studies showed a greater decrease in lean body mass among POC users. AUTHORS' We considered the overall quality of evidence to be low; more than half of the studies had low quality evidence. The main reasons for downgrading were lack of randomizations (NRS) and high loss to follow-up or early discontinuation.These 22 studies showed limited evidence of change in weight or body composition with use of POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. Those with multiyear data showed mean weight change was approximately twice as much at two to four years than at one year, but generally the study groups did not differ significantly. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.
Prior JC, 2016 Women's Reproductive Health
Non-sexually active adolescents are currently treated with combined hormonal contraception (CHC) for common experiences (e.g., cramps, acne) and serious problems (e.g., hypothalamic amenorrhea, heavy menstrual flow) for which it is not indicated, is ineffective, and is likely to cause negative long-term reproductive and bone effects. The importance to a woman's health of adolescent reproductive/bone maturation is described. Evidence is also provided to show the association of CHC use by adolescents with subfertility and inadequate bone growth. Ibuprofen is safer and more effective for cramps and heavy flow; cyclic progesterone builds bone in amenorrhea. In summary, a common, unscientific medical "habit" is compromising long-term reproductive and bone health in adolescents.
Wang YE et al., 2016 Ophthalmology
To investigate the association between oral contraceptive (OC) use and glaucoma prevalence in the United States. Cross-sectional study. A total of 3406 female participants, aged 40 years or older, from the 2005 to 2008 National Health and Nutrition Examination Survey, who reported a presence or absence of glaucoma or ocular hypertension completed both the vision and the reproductive health questionnaires and underwent eye examinations. Multivariate regression analysis was used to assess the correlation between OC use and self-reported glaucoma or ocular hypertension (n = 231 cases), controlling for potential confounders, including age, ethnicity, systemic comorbidities such as hypertension and stroke, ocular diseases such as cataract and diabetic retinopathy, and reproductive health factors, including age at menopause, age at menarche, history of hormone replacement therapy, and gynecological surgical history. The outcome variable was self-reported glaucoma or ocular hypertension. After adjusting for confounders, those with ≥3 years of OC use had greater odds (odds ratio, 1.94; 95% confidence interval, 1.22-3.07) of self-reported glaucoma or ocular hypertension. Other factors associated with higher glaucoma or ocular hypertension prevalence included older age, African American race, and later age at menarche. Oral contraceptive use may be associated with increased risk of self-reported glaucoma or ocular hypertension.
Hellwig K et al., 2016 PLoS One Open Access
The incidence of multiple sclerosis (MS) is rising in women. To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. We identified 400 women with incident MS/CIS and 3904 matched controls. Fortypercent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.
Fitzgerald JE, 2016 Natl Cathol Bioeth Q
In 2014, the American Academy of Pediatrics published its policy statement on contraception for adolescents, which provides, in effect, a mandate to temporarily sterilize all adolescents with long-acting reversible contraceptives for five to ten years. The author reviews the AAP guidelines and their effects on Catholic adolescents, their families, and adolescent health care providers. He then discusses medicolegal issues raised by the policy, outlines Catholic strategies for combating it, and proposes a diocese-based physician-led program for teaching and counseling elementary and high school students.
Brind J et al., 2015 Issues Law Med
As the HIV/AIDS epidemic continues to spread in Africa and Asia, use of the injectable contraceptive steroid DMPA is widespread and has been increasing. Since studies dating back to 1992 have suggested that DMPA may increase the transmission of HIV to women, we endeavored to determine if the extant epidemiological and biological evidence is sufficient to conclude that DMPA use constitutes a definite hazard to women's health. We searched Medline using the search terms: contraceptives or contraception AND HIV and searched bibliographies of articles thus identified. We included in the meta-analysis all studies examining the association between use of DMPA (or injectable contraceptives comprising mostly DMPA) and the presence (cross-sectional studies, n = 8) or acquisition (longitudinal studies, n = 16) of HIV+ status in women, using a random effects models to estimate odds ratios (ORs; cross-sectional studies) and hazard ratios (HRs; longitudinal studies). Studies were excluded if the comparison group included women using any form of steroidal contraception. Statistically significant positive associations between DMPA use and HIV positivity were observed both in cross-sectional (OR = 1.41, 95% CI 1.15 - 1.73) and longitudinal studies (HR = 1.49, 95% CI 1.28 - 1.73). The biological plausibility of increased vulnerability to HIV infection due to progestational action (via thinning of the vaginal epithelial barrier and immunosuppression) as well as glucocorticoid agonistic immunosuppression, are discussed. The epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission.
Champaneria R et al., 2015 Int Urogynecol J
Hormonal contraceptive use is common practice worldwide. Although the effects of hormone treatments in the pelvic region are well established, there is no clear evidence regarding their effects on incontinence, bladder, bowel, vaginal and sexual symptoms in premenopausal women. We hypothesized that hormonal contraceptives affect pelvic floor function. We therefore performed a comprehensive systematic review of published studies to determine the influence of hormonal contraception on pelvic floor functions. Electronic literature databases were searched from database inception to March 2015. Keywords and medical subject headings searched for included terms and word variations for 'contraception', and 'bowel', 'vaginal', 'sexual' and 'urinary' symptoms. Studies were eligible if they looked at these symptoms in women taking hormonal contraception. Two reviewers independently screened studies for inclusion, and extracted data on study characteristics, quality and results. Data were combined where possible. Of the 429 citations identified, 13 studies were included in the review. Data were meta-analysed where possible and presented as prevalence. The results indicate statistically significant links between interstitial cystitis and oral contraceptive use at any point (ever) (OR 2.31, 95 % CI 1.03 - 5.16; p = 0.04) and vulvar vestibulitis and current oral contraceptive use (OR 2.10, 95 % CI 1.26 - 3.49; p = 0.004). The evidence is unclear in other areas. Our results indicate that oral contraceptives may have an effect on pelvic floor function. They could increase the risk of painful bladder and vulvar vestibulitis, but their effect on dyspareunia is inconsistent. However, robustly collected prospective data to establish causal associations are needed.
Napolitano A et al., 2015 Eur J Contracept Reprod Health Care
The effect on body composition and in particular on fat mass (FM) of 12 months' use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause. An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months. FM did not change in the control group (- 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (- 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h). The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation.
Petersen N et al., 2015 Human brain mapping Open Access
Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology.
Vinogradova Y et al., 2015 BMJ Open Access
To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Two nested case-control studies. General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10,000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.
Andersen L et al., 2015 British journal of clinical pharmacology Open Access
Oral contraceptive use influences the risk for certain cancers. However, few studies have examined any link with risk of central nervous system tumours. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population-based setting. Using national administrative and health registries in Denmark to conduct a nationwide case-control study, we identified all women ages 15 to 49 years with a first time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age-matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e. combined oestrogen-progestagen or progestagen only, and duration of use (<1, 1 to <5, ≥5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders. We identified 317 cases and 2126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI 1.2, 2.0) and the OR increased with duration of use (long term, ≥5 years: OR 1.9; 95% CI 1.2, 2.9). The association between long term hormonal contraceptive use and glioma risk was most pronounced for progestagen only therapy (OR 2.4; 95% CI 1.1, 5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR 4.1; 95% CI 0.8, 20.8). Long term hormonal contraceptive use may increase the risk of glioma.
Morrison CS et al., 2015 PLoS Med Open Access
Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. Findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
Ralph LJ et al., 2015 Lancet Infect Dis Open Access
The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies. We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features. Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1·40, 95% CI 1·16-1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10-1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I(2) 51·1%, 95% CI 0-79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I(2) 54%, 0-88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86-1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88-1·37). Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive. None.
Lidegaard Ø, 2014 Expert Opin Drug Saf
This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages. Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased risk of venous thromboembolism as compared with nonusers, and about twice the risk as compared with users of products with norethisterone, levonorgestrel or norgestimate (low-risk products). Transdermal patches and vaginal ring belong to high-risk products. The risk of thrombotic stroke and myocardial infarction is increased 50 - 100% with use of combined products, with little difference in risk between different progestins. Progestin-only products do not confer any increased risk of venous or arterial thrombosis, except for progestin depot, which may double the risk of venous thrombosis. EXPERT Opinion: First choice in women below 35 years should be a combined low-risk pill, that is, with a second-generation progestin, with the lowest compliable dose of estrogen. Young women with risk factors of thrombosis such as age above 35 years, genetic predispositions, adiposity, polycystic ovary syndrome, diabetes, smoking, hypertension or migraine with aura should not use high-risk products, but should primarily consider progestin-only products, and be careful to use low-risk combined products.
Pletzer BA et al., 2014 Frontiers in Neuroscience Open Access
Hormonal contraceptives are on the market for more than 50 years and used by 100 million women worldwide. However, while endogenous steroids have been convincingly associated with change in brain structure, function and cognitive performance, the effects of synthetic steroids contained in hormonal contraceptives on brain and cognition have barely been investigated. In this article we summarize the sparse findings, describing brain structural, functional and behavioral findings from the literature and suggest that synthetic steroids may contribute to masculinizing as well as feminizing effects on brain and behavior. We try to identify methodological challenges, explain, how results on endogenous steroids may transfer into research on hormonal contraceptives and point out factors that need to be controlled in the study of hormonal contraceptive dependent effects. We conclude that there is a strong need for more systematic studies, especially on brain structural, functional and cognitive changes due to hormonal contraceptive use. The hormonal contraceptive pill is the major tool for population control. Hence, such behavioral changes could cause a shift in society dynamics and should not stay unattended.
Apter D et al., 2014 Fertility and sterility
To assess the pharmacokinetics and pharmacodynamics of levonorgestrel intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg (total content). Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies. Randomized, open-label, multicenter studies. PATIENT(S): Nulliparous and parous women. INTERVENTION(S): Levonorgestrel intrauterine system 13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 μg/24 h (total content 52 mg). MAIN OUTCOME MEASURE(S): Pharmacokinetics of LNG, ovulation rate, cervical function, and endometrium effects. RESULT(S): The in vivo LNG release rate of LNG-IUS 13.5 mg was approximately 14 μg/24 h after 24 days, declining progressively to 5 μg/24 h after 3 years. The average LNG serum concentration over 3 years of use was 74.3 ng/L, 114 ng/L, and 218 ng/L for LNG-IUS 13.5 mg, LNG-IUS 19.5 mg, and LNG-IUS 20 μg/24 h, respectively. All treatments showed very similar progestogenic effects on cervical mucus, with low and similar cervical scores throughout treatment. Ovulation was observed in the majority of women in all groups where assessment was possible, although there was a lower incidence of anovulation with LNG-IUS 13.5 mg and LNG-IUS 19.5 mg compared with LNG-IUS 20 μg/24 h. The progestogenic effect on the endometrium was marked in all three LNG-IUS groups. CONCLUSION(S): Levonorgestrel intrauterine system 13.5 mg and LNG-IUS 19.5 mg result in alower systemic exposure to LNG, lower incidence of anovulation, and similar progestin impact on the endometrium and cervical function compared with LNG-IUS 20 μg/24 h.
Crook AM et al., 2014 Hum Reprod Open Access
Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women? After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06-2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC). An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence. STUDY DESIGN, SIZE, A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) with a median age of 28 years were included in the analysis; 382 HIV seroconverted by 52 weeks follow-up; 10% of women-years were lost to follow-up before 52 weeks. PARTICIPANTS/MATERIALS, SETTING, Contraceptive use was reported at each 4-weekly visit. Cox proportional hazards (PH) models were used to estimate the effects of baseline and current use of injectable DMPA, injectable Net-En and OC compared with no HC, on the risk of HIV, adjusting for baseline and time-updated covariates. Causal effects for 52 weeks of HC use compared with no HC were estimated in a weighted Cox model, censoring women at deviation from baseline HC use (or non-use) or pregnancy. MAIN At baseline, 2499 (29%) women were on DMPA, 1180 (14%) on Net-En, and 1410 (16%) on OC; 3574 (40%) not on HC, started HC in follow-up. Adjusted hazard ratios (HR) for baseline HC use, compared with no HC, were 1.38 (95% confidence interval (CI) 1.07-1.78) for DMPA; 1.18 (0.86-1.62) for Net-En and 0.97 (0.68-1.38) for OC. The estimated causal effects of DMPA and Net-En over 52 weeks were: HR = 1.49 (95% CI 1.06-2.08) and HR = 1.31 (95% CI 0.62-1.61), respectively. LIMITATIONS, A main limitation of the study was that it was a secondary analysis of data from a study that was not designed to investigate this question. Despite our best efforts, we cannot exclude residual confounding to explain the effect of DMPA. The results of this study should be reviewed by the World Health Organization to determine whether current recommendations on the use of DMPA in settings with high HIV prevalence require modification. MDP is a partnership of African and European academic/government institutions with commercial organizations, which is funded by the UK Government (DFID and MRC), with support from IPM and EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: None.
Dal'Ava N et al., 2014 Contraception
Weight gain is a concern with the contraceptive depot-medroxyprogesterone acetate (DMPA); however, this issue remains controversial. The objective of this study was to compare body weight (BW) and body composition (BC) in DMPA and copper intrauterine device (IUD) users at baseline and after one year of use. We enrolled new DMPA users and age and weight matched new IUD users into this prospective study. Weight and height were measured, BC (fat and lean mass) was evaluated using dual-energy X-ray absorptiometry, and physical activity was assessed at baseline and at 12 months. Student's paired t test and the Wilcoxon paired test for matched samples were used. Ninety-seven women were enrolled for the study; 26 matched pairs continued using the initial method for at least one year, and completed the baseline and 12 month assessments. An increase of 1.9 kg occurred in BW (p=.02) in DMPA users at 12 months of use, resulting from an increase in fat mass of 1.6 kg (p=.03). Weight remained stable in IUD users; however, there was an increase in lean mass at 12 months of use (p=.001). The number of women practicing physical activity increased in this group. There was a significant difference between the groups regarding the variation in the percentage of central fat (p=.04). Weight gain in the DMPA group after the first year of use resulted from an increase in fat mass. Weight remained stable in the IUD group; however, an increase in lean mass and a reduction in localized abdominal fat mass occurred, possibly because more users were practicing physical activity. There was a greater increase in body weight in DMPA users compared to TCu380A IUD users in the first year of use of the contraceptive method. Furthermore, the weight increase in users of DMPA occurred principally as the result of an increase in fat mass. Physical activity probably could increase the lean mass in the users of TCu380A IUD.
Dinger J et al., 2014 Contraception
The "International Active Surveillance Study of Women Taking Oral Contraceptives" investigated the risks of shortand long-term use of an extended 24-day regimen of drospirenone and ethinylestradiol (DRSP24d) compared to established oral contraceptives (OCs) in a routine clinical setting. Prospective, controlled, noninterventional cohort study conducted in the United States and six European countries with three main cohorts: new users of DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs without DRSP). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular venous thromboembolism (VTE). Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. Primary statistical variable was the VTE hazard ratio (HR) for DRSP24d vs. non-DRSP. A total of 2285 study centers enrolled 85,109 women. Study participants were followed for 2 to 6 years, which generated 206,296 woman-years (WY) of observation. A low loss to follow-up of 3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs (LNG) showed similar incidence rates of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events. VTE incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8 VTE/10,000 WY, respectively. Adjusted HRs for DRSP24d vs. non-DRSP and DRSP24d vs. LNG were 0.8 [95% confidence interval (CI), 0.5-1.3] and 0.8 (95% CI, 0.4-1.5). DRSP24d, DRSP21d, non-DRSP and LNG use was associated with similar risks of serious adverse events, and particularly VTE, during routine clinical use. The 24-day regimen of drospirenone-containing combined OCs is associated with similar risks of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events compared to 21-day regimens of drospirenone-containing combined OCs, OCs without drospirenone and LNGs.
Huijbregts RP et al., 2014 Contraception Open Access
The potential effect of hormonal contraception on HIV-1 acquisition and transmission represents an important public health issue. Several observational studies have suggested an association between the use of hormonal contraception, in particular injectable depot medroxyprogesterone acetate (DMPA), and an increased risk of HIV-1 acquisition and transmission. We and others have previously demonstrated that DMPA acts as a potent inhibitor of innate and adaptive immune mechanisms. The study presented here addresses the immunomodulatory properties of several common progestins with a potential to replace DMPA. To identify safe alternatives to DMPA, we tested the effect of commonly used progestins on the function of human primary T cells and plasmacytoid dendritic cells (pDCs) obtained from the blood of healthy premenopausal women. Medroxyprogesterone acetate (MPA) inhibited the activation of T cells and pDCs in response to T cell receptorand Toll-like receptor-mediated activation at physiological concentrations. Etonogestrel exerted a partial suppressive activity at high concentrations. In sharp contrast, norethisterone (NET) and levonorgestrel (LNG) did not exhibit detectable immunosuppressive activity. Evidence indicating the immunosuppressive properties of DMPA strongly suggests that DMPA should be discontinued and replaced with other forms of long-term contraception. Since NET and LNG do not exert immunosuppressive properties at physiological concentrations, these progestins should be considered as alternative contraceptives for women at high risk for HIV-1 infection. The presented data suggest that, at physiological levels, the progestins NET and LNG do not suppress cytokine production by immune cells and should be considered as alternatives to DMPA; however, more in vivo testing is needed to confirm this data.
Hapgood JP et al., 2014 Am J Reprod Immunol
Whether hormonal contraceptives increase HIV-1 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off-target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET-EN), widely used as injectable contraceptives in sub-Saharan Africa. While most high-quality clinical studies find no increased risk for HIV-1 acquisition with oral contraception or injectable NET-EN, most do find an increase with MPA, particularly in young women. Furthermore, mounting evidence from animal, ex vivo and biochemical studies are consistent with MPA acting to increase HIV-1 acquisition and pathogenesis, via mechanisms involving glucocorticoid-like effects on gene expression, in particular genes involved in immune function. We report that MPA, unlike NET and progesterone, represses inflammatory genes in human PBMCs in a dose-dependent manner, via the glucocorticoid receptor (GR), at concentrations within the physiologically relevant range. These and published results collectively suggest that the differential GR activity of MPA versus NET may be a mechanism whereby MPA, unlike NET or progesterone, differentially modulates HIV-1 acquisition and pathogenesis in target cells where the GR is the predominant steroid receptor expressed.
Battaglia C et al., 2014 The journal of sexual medicine
Oral contraceptives (OC) are effective for birth control and have good cycle control and tolerability. However, the hormonal components could modify mood and libido. The aim of this study is to evaluate the genital vascular effects and sexual behavior of an OC containing 30 μg ethinyl estradiol and 3 mg drospirenone in comparison with a flexible combined contraceptive vaginal ring. Forty women underwent a sonographic assessment of the clitoral anatomy and vascularization and were administered the McCoy Female Sexuality Questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). Estradiol, androstenedione, testosterone, and SHBG were assayed. Free Androgen Index (FAI) and Free Estrogen Index (FEI) were calculated. The patients were randomly submitted to OC (group I; n = 21) or vaginal ring (group II; n = 19). Ultrasonographic clitoral volume, pulsatility index (PI) of dorsal clitoral arteries, MFSQ, BDI, and hormonal and biochemical assays were analyzed. After therapy, the testosterone levels were reduced in both groups, whereas estradiol decreased only in group I women. The SHBG increased in all the subjects, and both FAI and FEI decreased. The clitoral volume decreased in all the women. The PI of the dorsal clitoral artery increased only in patients on OC. The hormonal contraception was associated, in both studied groups, with a significant decrease of the two-factor Italian MFSQ score, which was more marked in OC users. In group I subjects, there was a reduction of the number of intercourse/week and a reduction of orgasm frequency during intercourse. The pain during intercourse worsened after OC use. The vaginal ring users reported a vaginal wetness. Six-month treatment with hormonal contraception is associated with a diminished MFSQ score. However, the frequency of sexual intercourse and orgasm was reduced only by the use of OC. The OC use was associated with increased pain during intercourse.
Gallo MF et al., 2014 Cochrane Database Syst Rev Open Access
Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. Selection Criteria: All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. Data Collection and Analysis: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. MAIN We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied. AUTHORS' Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non-hormonal group to control for other factors, including changes in weight over time.
Keyes KM et al., 2013 Am J Epidemiol Open Access
An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.
Little AC et al., 2013 Psychoneuroendocrinology
Millions of women use hormonal contraception and it has been suggested that such use may alter mate preferences. To examine the impact of oral contraceptive (pill) use on preferences, we tested for within-subject changes in preferences for masculine faces in women initiating pill use. Between two sessions, initiation of pill use significantly decreased women's preferences for male facial masculinity but did not influence preferences for same-sex faces. To test whether altered preference during pill use influences actual partner choice, we examined facial characteristics in 170 age-matched male partners of women who reported having either been using or not using the pill when the partnership was formed. Both facial measurements and perceptual judgements demonstrated that partners of women who used the pill during mate choice have less masculine faces than partners of women who did not use hormonal contraception at this time. Our data (A) provide the first experimental evidence that initiation of pill use in women causes changes in facial preferences and (B) documents downstream effects of these changes on real-life partner selection. Given that hormonal contraceptive use is widespread, effects of pill use on the processes of partner formation have important implications for relationship stability and may have other biologically relevant consequences.
Welling LL, 2013 Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior
Although female use of hormonal contraceptives (HCs) has been associated with a variety of physical side effects, the psychological and behavioral side effects have received comparatively little attention until recently. Indeed, the long-term impact of HC use on human psychology has been vastly under-researched and has only recently become a focus for mainstream scholars. Women who use HCs report higher rates of depression, reduced sexual functioning, and higher interest in short-term sexual relationships compared to their naturally-cycling counterparts. Also, HC use may alter women's ability to attract a mate, as well as the mate retention behaviors in both users and their romantic partners. Some evidence even suggests that HC use alters mate choice and may negatively affect sexual satisfaction in parous women, with potential effects on future offspring. Interestingly, HCs have become a standard method of population control for captive nonhuman primates, opening up exciting avenues for potential comparative research. Here, the existing literature on the psychobehavioral effects of HCs in humans and nonhuman primates is reviewed and discussed. The potential resulting downstream consequences for the path of human evolution and recommendations for how future research could tease apart the underlying causes of these psychobehavioral effects of HC use are discussed, including suggestions for research involving nonhuman primates.
Heidarzadeh Z et al., 2013 J Stroke Cerebrovasc Dis
Combined oral contraceptives (COCs) are considered for their thrombogenicity and the risk of premature atherosclerosis and the stroke caused by them. The aim of this study was to evaluate the relationship between chronic use of low-dose COCs (ethinyl estradiol 30 mcg + levonorgestrel 150 mcg) and endothelial dysfunction and intima-media thickness. In a cross-sectional study, in 2011-2012, 60 healthy premenopausal women (30 cases of COC consumers and 30 controls as nonconsumers), aged between 25 and 45 years, participated in this study. They were current users for at least a 3-year period. Brachial artery flow-mediated dilatation (FMD) and common carotid artery intima-media thickness (CCA-IMT) were measured for the patients. The mean duration of COC consumption was 54.03 ± 27.27 months in the case group. There was a significant FMD% difference between 2 groups of cases and controls: 11 ± 3.53 versus 15.80 ± 9.22 (P = .01). In addition, a significant mean CCA-IMT thickness difference was detected: .53 ± .07 versus .44 ± .08 (P = .00). However, after multiple regression analysis and adjusting for body mass index (BMI), in COC users, no significant association between COC consumption duration and FMD% and mean CCA-IMT was observed. Prolonged used of low-dose COCs may cause changes in both endothelial function (measured by FMD%) and endothelial structure (measured by CCA-IMT). There was a nonsignificant inverse relationship between the duration of COC ingestion and FMD% and a nonsignificant positive relationship with CCA-IMT. Our results are in favor of early atherosclerotic changes in prolonged users of COCs.
Le Moigne E et al., 2013 Thromb Res
The risk of recurrent venous thromboembolism (VTE) in young women after a first oestrogen contraception associated VTE episode is unknown. This uncertainty has an impact on the decision whether to stop anticoagulant treatment. Our objective was to assess the risk of recurrent VTE in women after a first VTE episode on oestrogen contraception. This was a prospective cohort study in which we consecutively enrolled between 1992 and 2011 all women under 50years with a first objectively confirmed VTE. The incidence of recurrent VTE during follow-up after stopping anticoagulation was compared between women users and non-users of combined oral contraception (COC) at the time of index VTE. Of the 241 women aged 50 or younger seen for a first VTE and followed-up after stopping anticoagulation, there were 180 COC-users and 61 non-users. Median duration of follow-up off-anticoagulants was 66 months (interquartile range: 33-103). There were 14 recurrences in COC-users and 5 cases in non-users. No significant association was found between exposure to COC and the incidence of recurrent VTE after adjustment for age or after restricting the analysis to major unprovoked incidence rate of recurrence 17.9/1,000/year (95% CI: 9.6-33.2) in women with COC as compared with 17.6/1,000/year (95% CI: 6.6-47) with an incidence ratio of 0.7 (95% CI: 0.2-2.4, p=0.59). The risk of recurrent VTE is low in young women after a first VTE. However, this risk is not significantly lower in women after a first VTE while exposed to combined oral contraception.
Tomasicchio M et al., 2013 PLoS One Open Access
The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4(+) T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4(+) T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptorselective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPAand Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4(+) T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4(+) T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and progression of diseases such as HIV-1.
Vickery Z et al., 2013 Contraception Open Access
Concerns about weight gain may influence contraceptive use. We compared the change in body weight over the first 12 months of use between women using the etonogestrel (ENG) implant, the levonorgestrel intrauterine system (LNG-IUS) or depot medroxyprogesterone acetate (DMPA) with women using the copper intrauterine device (IUD). This was a substudy of the Contraceptive CHOICE Project, a prospective cohort study of 9256 women provided no-cost contraception. Women who had been using the ENG implant, LNG-IUS, DMPA or copper IUD continuously for at least 11 months were eligible for participation. We obtained body weight at enrollment and at 12 months and compared the weight change for each progestin-only method to the copper IUD. We enrolled a total of 427 women: 130 ENG implant users, 130 LNG-IUS users, 67 DMPA users and 100 copper IUD users. The mean weight change (in kilograms) over 12 months was 2.1 for ENG implant users [standard deviation (SD)=6.7]; 1.0 for LNG-IUS users (SD=5.3); 2.2 for DMPA users (SD=4.9) and 0.2 for copper IUD users (SD=5.1). The range of weight change was broad across all contraceptive methods. In the unadjusted linear regression model, ENG implant and DMPA use were associated with weight gain compared to the copper IUD. However, in the adjusted model, no difference in weight gain with the ENG implant, LNG-IUS or DMPA was observed. Only Black race was associated with significant weight gain (1.3 kg, 95% confidence interval=0.2-2.4) when compared to other racial groups. Weight change was variable among women using progestin-only contraceptives. Black race was a significant predictor of weight gain among contraceptive users.
McCoy SI et al., 2013 AIDS
To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe. Secondary data analysis of 4913 sexually active women aged 18-49 years followed for up to 24 months in the Methods for Improving Reproductive Health in Africa (MIRA) phase III effectiveness trial of the diaphragm and lubricant gel for HIV prevention. Participants were interviewed quarterly about contraception and sexual behavior and were tested for pregnancy, HIV, and other sexually transmitted infections. We used a Cox proportional hazards marginal structural model, weighted by the inverse probability of hormonal contraception use, to compare the risk of HIV acquisition among nonpregnant women reporting use of combined oral contraceptive pills (COC), progestin-only pills (POP), and/or injectable hormonal contraception to women not using these methods. During the study, 283 participants seroconverted. Use of oral contraceptives (POP or COC) was not associated with HIV risk [adjusted hazard ratio (HRa) = 0.86, 95% confidence interval (CI) 0.32, 1.78]. Injectable hormonal contraception was associated with a small nonsignificant risk of HIV infection (HR(a) = 1.34, 95% CI 0.75, 2.37). The effect of injectable hormonal contraception was similar in the unweighted site-adjusted only (HR(a) = 1.32, 95% CI 1.00, 1.74) and baseline factor adjusted models (HR(a) = 1.27, 95% CI 0.94, 1.72). In this study, oral contraceptives were not associated with HIV acquisition. There is substantial uncertainty in the effect of injectable hormonal contraception on HIV risk. These findings underscore the importance of dual protection with condoms and the need for diverse contraceptive options for women at risk of HIV infection.
Sidney S et al., 2013 Contraception
Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile. All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study. The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes. In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not.
Talukdar N et al., 2012 Obstetrics and gynecology
To estimate whether there is any association of long-term use of combined oral contraceptive pills (OCP) with adverse endometrial growth. We reviewed the charts of 137 patients with history of OCP use undergoing endometrial preparation with estrogen for frozen embryo transfer. Endometrial thickness was measured by transvaginal ultrasonography on day 10 after menses and patients were divided into two groups (less than 7 mm and 7 mm or more). Thirty patients had endometrial thickness less than 7 mm and 107 had thickness of 7 mm or more. Mean years of combined OCP use in each group were 9.8±4.54 and 5.8±4.52, respectively (P<.001). With 10 years of combined OCP use as the threshold, the difference between the two groups (63.35% users in less than 7 mm group compared with 28.04% in the 7 mm or more thickness group) was highly significant (P<.001 by Fisher exact test), with an odds ratio of 4.43 (95% confidence interval 1.89-10.41). Past use of 5 years of OCPs was also associated with a significant (P=.002) difference in endometrial thickness. The mean endometrial thicknesses on cycle day 10 in patients using combined OCP for less than 10 years and 10 years or more were 9.54±1.88 mm and 8.48±2.33 mm, respectively, with P=.007. The mean endometrial thickness was 9.72±1.69 mm in less than 5 years and 8.81±2.23 mm in 5 or more years of use, respectively (P=.008). Cycle cancellation rates in the less than 7 mm group and 7 mm or greater endometrial thickness group were 23% and 4%, respectively (P=.002), but there was no difference in the clinical pregnancy rates between the two groups (13% compared with 27%, respectively; P=.15). Long-term combined OCP use (5 years or more) can potentially affect optimal endometrial growth, leading to a higher cancellation rate and longer stimulation in frozen embryo transfer cycles. These findings suggest a previously unidentified adverse effect of long-term combined OCP use in women who are anticipating future fertility. II.
Lidegaard Ø et al., 2012 N Engl J Med
Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting. In this 15-year Danish historical cohort study, we followed nonpregnant women, 15 to 49 years old, with no history of cardiovascular disease or cancer. Data on use of hormonal contraception, clinical end points, and potential confounders were obtained from four national registries. A total of 1,626,158 women contributed 14,251,063 person-years of observation, during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred. As compared with nonuse, current use of oral contraceptives that included ethinyl estradiol at a dose of 30 to 40 μg was associated with the following relative risks (and 95% confidence intervals) for thrombotic stroke and myocardial infarction, according to progestin type: norethindrone, 2.2 (1.5 to 3.2) and 2.3 (1.3 to 3.9); levonorgestrel, 1.7 (1.4 to 2.0) and 2.0 (1.6 to 2.5); norgestimate, 1.5 (1.2 to 1.9) and 1.3 (0.9 to 1.9); desogestrel, 2.2 (1.8 to 2.7) and 2.1 (1.5 to 2.8); gestodene, 1.8 (1.6 to 2.0) and 1.9 (1.6 to 2.3); and drospirenone, 1.6 (1.2 to 2.2) and 1.7 (1.0 to 2.6), respectively. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (1.3 to 1.9) and 1.6 (1.1 to 2.1); gestodene, 1.7 (1.4 to 2.1) and 1.2 (0.8 to 1.9); and drospirenone, 0.9 (0.2 to 3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5). Although the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg and by a factor of 1.3 to 2.3 with those that included ethinyl estradiol at a dose of 30 to 40 μg, with relatively small differences in risk according to progestin type. (Funded by the Danish Heart Association.).
Khalili H et al., 2012 Gut Open Access
Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC). To determine whether this association is confounded or modified by other important lifestyle and reproductive factors. A prospective cohort study was carried out of 117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2 years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs. Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (pheterogeneity=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD. In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.
Lidegaard O et al., 2012 BMJ Open Access
To assess the risk of venous thrombosis in current users of non-oral hormonal contraception. Historical national registry based cohort study. Four national registries in Denmark. All Danish non-pregnant women aged 15-49 (n=1,626,158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010. Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis. Within 9,429,128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10,000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7). Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10,000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.
Rodriguez D et al., 2012 Linacre Q Open Access
Hispanics are the largest minority group in the U.S. and they contribute to over 50 percent of Catholics under the age of 25. The purpose of this study was to determine the patterns of contraceptive use (current and ever), natural family planning (NFP), and abortion among U.S. Hispanic women between the ages of 15 and 44 years and to compare their patterns of use to non-Hispanic women of the same age range. A particular interest was to determine the influence of faith on the choice of family-planning methods among the sexually active U.S. Catholic Hispanic women. Data for this study came from the National Survey of Family Growth 2006-2008, which included 1,613 Hispanic and 5,743 non-Hispanic women between the ages of 15 and 44. Approximately 57 percent of the Hispanic women are Catholic. In general, U.S. Hispanic women had significantly less frequent use of the hormonal pill, male condom, withdrawal, and vasectomy (of male partner) but more frequent use of the IUD and Depo-Provera compared to non-Hispanic women. There was little use of NFP and no difference in the frequency of reported abortion. Catholic Hispanic women had significantly less frequent use of the male condom, the Pill, vasectomy, and abortion and more use of NFP compared to non-Catholic Hispanic women. Although there is some positive influence of faith among the sexually active Hispanic women of reproductive age, overall, the amount of ever use of sterilization (21 percent), condom use (80 percent), Pill use (66 percent), and Depo-Provera (30 percent) is remarkable. The more frequent use of Depo-Provera and the IUD might reflect the economic level of the participants and the use of federally funded family-planning services.
Svendal G et al., 2012 J Affect Disord
Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women. This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented. After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking. This study is cross-sectional, which precludes any determination regarding the direction of the relationships. These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders.
Roberts SC et al., 2012 Proceedings. Biological sciences Open Access
Hormonal variation over the menstrual cycle alters women's preferences for phenotypic indicators of men's genetic or parental quality. Hormonal contraceptives suppress these shifts, inducing different mate preference patterns among users and non-users. This raises the possibility that women using oral contraception (OC) choose different partners than they would do otherwise but, to date, we know neither whether these laboratory-measured effects are sufficient to exert real-world consequences, nor what these consequences would be. Here, we test for differences in relationship quality and survival between women who were using or not using OC when they chose the partner who fathered their first child. Women who used OC scored lower on measures of sexual satisfaction and partner attraction, experienced increasing sexual dissatisfaction during the relationship, and were more likely to be the one to initiate an eventual separation if it occurred. However, the same women were more satisfied with their partner's paternal provision, and thus had longer relationships and were less likely to separate. These effects are congruent with evolutionary predictions based on cyclical preference shifts. Our results demonstrate that widespread use of hormonal contraception may contribute to relationship outcome, with implications for human reproductive behaviour, family cohesion and quality of life.
Dal'Ava N et al., 2012 Contraception
There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD). A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (±2 years) and body mass index (BMI, kg/m², ±2). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat. There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean±SD) (34.4±7.5 vs. 33.9±8.0 years), BMI (25.3±4.1 vs. 25.9±4.1) and number of pregnancies (1.9±0.2 vs. 1.7±0.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use. Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes.
Battaglia C et al., 2012 The Journal of Sexual Medicine
Oral contraceptives (OCs) induce mood and libido changes. The aim of this study was to evaluate in young, eumenorrheic, healthy women the sexual behavior and the genital vascular effects of an OC containing 30 µg ethinylestradiol (EE) and 3 mg drospirenone (DRSP). The main outcome measures are McCoy Female Sexuality Questionnaire (MFSQ), the labia minora thickness and vaginal introitus area, the pulsatility index (PI) of clitoral and labia minora arteries, and hormonal and biochemical assays. Twenty-two adult, eumenorrheic, healthy women were administered the two-factor Italian MFSQ. The labia minora thickness was studied by two-dimensional ultrasonographic, and the clitoral and labia minora arteries were evaluated by color Doppler; three-dimensional static volumes of the vulvar area were calculated. Hormonal (estradiol, androstenedione, and testosterone) and biohumoral (sex hormone binding globulin) parameters were assayed. Subjects were studied in baseline conditions and after 3 months of therapy with an OC (Yasmin®, Bayer-Schering Italia, Milan, Italy; −30 µg EE + 3 mg DRSP). After 3-month treatment, the labia minora thickness and the vaginal introitus area significantly decreased in comparison with the baseline values, whereas the PI of the dorsal clitoral artery and the posterior labial artery significantly increased. The OC use induced a significant decrease of the two-factor Italian MFSQ score, a reduction of the number of intercourse/week, and a reduction of the frequency of orgasm during intercourse. The item 18 (pain during intercourse) worsened after OC. The treatment with Yasmin® (Bayer-Schering Italia) is associated with increased pain during intercourse, with decreased libido and spontaneous arousability, and with diminished frequency of sexual intercourse and orgasm.
Wand H et al., 2012 AIDS
To investigate the association between hormonal contraceptives and risk of HIV-1 seroconversion and prevalence of other sexually transmitted infections. Prospective cohort. The study population was 2,236 HIV-negative women who were screened in a biomedical intervention trial in Durban, South Africa. The association between the use of hormonal contraceptives and risk of HIV-1 seroconversion was modeled using Cox proportional hazards regression analysis. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections were assessed using logistic regression models. Hormonal injectables were the most common method of contraceptives (46.47%) followed by condom use (28.04%). Overall, compared with women who reported using condoms or other methods as their preferred form of contraceptive, those who reported using hormonal contraceptives (injectables and oral pills) were less likely to use condoms in their last sexual act. Using hormonal injectables during the study was significantly associated with increased risk for HIV-1 infection [adjusted hazard ratio 1.72, 95% confidence interval (CI) 1.19-2.49, P = 0.005]; hormonal injectables were also significantly associated with higher prevalent of C. trachomatis infections (adjusted odds ratio 2.46, 95% CI 1.52-3.97, P < 0.001). Hormonal injectables are highly effective and well tolerated family planning methods and have played an important role in reducing unplanned pregnancies and maternal and infant mortality. However, they do not protect against HIV-1 and other sexually transmitted infections. This study reinforces the importance of comprehensive contraceptive counseling to women about the importance of dual protection, such as male condoms and hormonal contraceptives use.
Lundgren R et al., 2012 Reproductive Health
Introducing a new method into family planning programs requires careful attention to ensure it meets an actual need and has a positive effect on program goals. The Standard Days Method® is a fertility awareness-based method of family planning that is being introduced into family planning programs in countries around the world. It is different from other methods offered by programs, and may bring new couples into family planning, and increase contraceptive prevalence. The study assesses the effect on contraceptive use and prevalence of Introducing Standard Days Method into existing family planning services in whole regions of India, Peru, and Rwanda. In collaboration with the Ministry of Health, health providers were given a contraceptive update on all methods, then trained in counseling on Standard Days Method. Efforts were made to promote demand in the context of informed choice. Routine monthly service statistics in control and intervention areas were used to assess the effect of Standard Days Method introduction at the clinic level; baseline and endline household-based surveys were undertaken to obtain results at the community level (n > 3400 women at endline). Demand for the method is evident in countries with different levels of contraceptive prevalence. The method attracts couples new to family planning, and introducing it into services may increase overall contraceptive prevalence. Introducing Standard Days Method into existing family planning has the potential of benefiting men and women in diverse settings and populations. This study illustrates the critical role of evidence in scaling up a health innovation.
Heffron R et al., 2012 Lancet Infect Dis Open Access
Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Findings: Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6-24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06-3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8-24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12-3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Interpretation: Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. US National Institutes of Health and the Bill & Melinda Gates Foundation.
Morrison CS et al., 2011 AIDS
To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa. We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16-24 years) in particular. Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI 0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96-2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users. In this study conducted among South African women, hormonal contraception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies.
Norouzi V et al., 2011 Anadolu Kardiyol Derg
Increased levels of homocysteine and C-reactive protein (CRP) are considered as independent risk factors for atherosclerosis. As the level of these factors is affected by sex hormones, a population-based assessment of their changes following oral contraceptive therapy is needed to avoid the side effects that might arise of these variations. To this aim, the present study was to investigate the effect of combined oral contraceptive (OCP) on CRP and homocysteine levels among young healthy women. We conducted an observational cross-sectional analysis of 90 healthy, non-obese women (mean age 25 years and body-mass index 22 kg/m2). Forty-five healthy women on OCP and 45 healthy controls were studied for CRP and homocysteine levels by enzyme-linked immunosorbent assay (ELISA). Unpaired t test and Chi-square test were used for comparison of variables between oral contraceptive users and non-oral contraceptive users. The results showed that the homocysteine (13.268±3.475 vs. 7.288±2.621 µmol/L) and CRP (5863.0±1349.5 vs. 1138.3±691.12 ng/ml) levels were significantly higher in women receiving OCP in comparison with the control group (p=0.027 and p<0.001, respectively). The alteration in homocysteine and CRP levels could be attributed to the OCP suggesting that use of these pills should be reviewed in women with increased risk of atherosclerosis and other cardiovascular risk factors.
Gronich N et al., 2011 CMAJ Open Access
Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives. Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors. We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431,223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10,000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15-1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02-2.65). There was no increase in the risk of arterial thrombosis with drospirenone. Interpretation: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to secondand third-generation combined oral contraceptives.
Lidegaard Ø et al., 2011 BMJ Open Access
To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose. National historical registry based cohort study. Four registries in Denmark. Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009. Relative and absolute risks of first time venous thromboembolism. Within 8,010,290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10,000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year. After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.
Toffol E et al., 2011 Hum Reprod
The effects of oral contraceptives (OCs) on mental health are not clear, and no study has been focused on the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on mental health. The aim of this study was to analyse the association between the use of OCs and the LNG-IUS and psychological well-being and psychopathology. The associations between the current use of OCs and the LNG-IUS, and their duration versus mood symptoms [Beck Depression Inventory (BDI)], psychological well-being [(General Health Questionnaire-12 (GHQ-12)] and recent psychiatric diagnoses [(Composite International Diagnostic Interview (CIDI)] were examined among women who participated in the Finnish-population-based Health 2000 study. Analyses were performed on the 30to 54-year-old sample (n = 2310); some of the analyses were extended to include the younger age group (18to 54-year-old sample; n = 3223). Overall, hormonal contraception was well tolerated with few significant effects on psychological well-being. The length of OC use was inversely associated with some BDI items ('dissatisfaction, irritability, lost interest in people, earlier waking and lost interest in sex'), and directly associated with 'worries about one's health' (BDI) and with a current diagnosis of 'alcohol dependence' (CIDI). The current use of the LNG-IUS was inversely associated with 'earlier waking' (BDI) and with 'impaired concentration' (GHQ), while the length of LNG-IUS use was inversely associated with 'strain' (GHQ). The influence of hormonal birth control on mental health is modest and mainly favourable. The length of current OC use seems to have some beneficial effects on mood although the longer the duration of use, the greater the association with a diagnosis of alcohol dependence. Knowledge of the use of hormonal contraception might be of value when assessing psychopathology in women. The cross-sectional design, with partly retrospective data collection, precludes any causal conclusions.
Jick SS et al., 2011 BMJ Open Access
To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel. Nested case-control and cohort study. The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans. The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time. Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives. 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100,000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100,000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8). The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account.
Parkin L et al., 2011 BMJ Open Access
To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel. Nested case-control study. UK General Practice Research Database. Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case. Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression. 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100,000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100,000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7). These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.
Hickson SS et al., 2011 J Hypertens
The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women. Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed. Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups. Use of the OCP is associated with elevated pulse pressure and SV and a small increase in aPWV in young women. The longer term implications of these effects require further investigation.
Griksiene R et al., 2011 Psychoneuroendocrinology
Cognitive abilities, such as verbal fluency and mental rotation, are most sensitive to changes in sex steroids but poorly studied in the context of hormonal contraceptive usage. Therefore, we investigated the performance of mental rotation and verbal fluency in young (21.5±1.8 years) healthy oral contraceptive (OC) users (23 women) and non-users (20 women) during the follicular, ovulatory and luteal phases of the menstrual cycle. Salivary 17β-estradiol, progesterone and testosterone levels were assayed to evaluate hormonal differences between groups and the phases of the menstrual cycle. To assess the effects of progestins having androgenic/anti-androgenic properties, OC users were subdivided into the third and new generation OC users. In addition, positive and negative affects as factors possibly affecting cognitive performance were evaluated. Salivary 17β-estradiol and progesterone levels were significantly lower in hormonal contraception users. Level of salivary testosterone was slightly lower in the OC users group with significant difference only during ovulatory phase. Naturally cycling women performed better on verbal fluency task as compared to OC users. Subjects who used the third generation (androgenic) OCs generated significantly fewer words as compared to new generation (anti-androgenic) OC users and non-users. The third generation OC users demonstrated significantly longer RT in MRT task as compared to non-users. The MRT, verbal fluency and mood parameters did not depend on the phase of menstrual cycle. The parameters of the PANAS (Positive and Negative Affect Schedule) scales did not differ between OC users and non-users. Our findings show that hormonal contraception has an impact on verbal and spatial abilities. Different performances between users of oral contraceptives with androgenic and anti-androgenic properties suggest an essential role for the progestins contained in OCs on cognitive performance.
Choi J et al., 2010 J Obstet Gynaecol Can
To assess physicians' knowledge, attitudes, and practice with respect to four evidence-based natural family planning (NFP) Standard Days, cervical mucus, basal body temperature, and the lactational amenorrhea method. We undertook a cross-sectional survey of a random sample of family physicians and all gynaecologists in British Columbia (n = 460) who have women of reproductive age in their practice, as well as all affiliated residents (n = 239). Main outcome measures were (1) physicians' attitudes towards NFP and their perceptions of its effectiveness; (2) the relationship between physicians' demographic factors, their personal experience or beliefs, and their attitudes and knowledge; and (3) how these factors affect the counselling physicians offer their patients. The survey response rate was 44%. Only 3% to 6% of physicians had correct knowledge of the effectiveness in perfect use of the NFP methods cited in this study. Fifty percent of physicians who responded mention NFP to their patients as an option for contraception, and 77% of physicians mention NFP as an option to couples trying to conceive. Family physicians and residents were much more likely than gynaecologists or gynaecology residents to mention NFP during counselling. Older physicians were more likely to mention NFP than younger physicians and also had more personal experience with NFP. Most physicians in our study underestimated the effectiveness of NFP methods, and only a small proportion of physicians provide information about NFP during contraceptive counselling. Physicians need better understanding of modern methods of NFP to provide evidence-based contraceptive counselling to selected highly motivated patients who prefer NFP as a contraceptive choice.
Dinger J et al., 2010 J Fam Plann Reprod Health Care
The primary objective of the study was to clarify whether the use of the oral contraceptive 2 mg dienogest/30 microg ethinylestradiol (DNG/EE) is associated with a higher risk of venous thromboembolism (VTE) than the use of other combined oral low-dose contraceptives (i.e. containing < or =30 microg EE), particularly oral contraceptives containing levonorgestrel (LNG). The secondary objective was to investigate the VTE risk associated with drospirenone/ethinylestradiol (DRSP/EE) in comparison to low-dose LNG/EE. This German community-based, case-control study recruited VTE cases from the primary care sector. Eligible cases were women aged 15-49 years with a VTE between January 2002 and February 2008. Four controls (women without a confirmed or potential VTE before the index date) were matched by age and region to each case. Medical information relevant for the assessment of VTE was abstracted from patient charts. Data on personal characteristics of the patients were collected via self-administered questionnaires. At the end of the study a blinded adjudication of the reported VTE was conducted. Conditional logistic regression techniques were used, adjusting for nine potential confounders, including personal history of VTE, family history of VTE, body mass index, duration of current combined oral contraceptive (COC) use and smoking. A total of 680 VTE cases and 2720 corresponding controls were analysed. The mean age of cases and controls was - as a result of matching - almost identical (36.1 years).
Pantoja M et al., 2010 Contraception
Weight gain is a frequent reason for discontinuing the contraceptive with depot-medroxyprogesterone acetate (DMPA). This 3-year retrospective cohort study assessed body mass index (BMI; kg/m(2)) variations in 379 current or past DMPA users compared to TCu380A intrauterine device (IUD) users matched for age and BMI, categorized into G1 (normal weight), G2 (overweight) or G3 (obese) according to baseline BMI. Variations in weight and BMI were evaluated using analysis of variance. BMI increased progressively in all groups but significantly more in G1 and G2 DMPA users compared to nonusers and according to duration of use. In the G3 subgroup, weight trends were similar in the DMPA and IUD users. Normal and overweight women increased BMI with DMPA use; however, obese women did not increase weight. Weight increase in DMPA users could be associated with metabolic alterations related to duration of use in normal and overweight women and to alterations already present in obese women. Prospective studies are required to determine triggering factors. DMPA use or=30.
Waller DK et al., 2010 Epidemiology
Oral contraceptives (OCs) are the most commonly used reversible contraceptive method among US women. Although the majority of previous studies have reported no association between OC use during pregnancy and birth defects, some studies have reported increased occurrence of neural tube defects, limb reduction defects, and urinary tract anomalies. We assessed OC use among mothers who participated in the multisite, case-control, National Birth Defects Prevention Study. Mothers of 9986 infants with 32 types of birth defects and 4000 infants without birth defects were included. Maternal OC use during the first 3 months of pregnancy was associated with an increased odds ratio for 2 of 32 birth defects: hypoplastic left heart syndrome (adjusted odds ratio = 2.3 [95% confidence interval = 1.3-4.3) and gastroschisis (1.8 [1.3-2.7]). Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects, our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall, our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.
Palan PR et al., 2010 Obstetrics and gynecology international
The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research.
van Hylckama Vlieg A et al., 2009 BMJ Open Access
To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands. Population based case-control study. Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht). Premenopausal women <50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls. First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf's method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model. Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives. Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.
Lidegaard Ø et al., 2009 BMJ Open Access
To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. National cohort study. Denmark, 1995-2005. Danish women aged 15-49 with no history of cardiovascular or malignant disease. Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.
Cagnacci A et al., 2009 Contraception
The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity (SI). This is a prospective, randomized study performed in the University Hospital. Subjects were healthy lean young women, needing a hormonal contraceptive, randomly allocated to receive for 6 months (a) an oral contraceptive (OC) containing 30 mcg ethinylestradiol (EE)/150 mcg desogestrel (DSG) (high-estrogen group; n=12), (b) an OC containing 20 mcg EE/150 mcg DSG (low-estrogen group; n=12) and (c) a vaginal ring contraceptive releasing, per day, 15 mcg EE/120 mcg etonorgestrel, the active DSG metabolite (n=12). SI and glucose utilization independent of insulin (Sg) were evaluated by the minimal model method. Modifications of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol and triglycerides were also evaluated. Sg did not vary with any treatment. SI decreased during OCs (5.74+/-0.49 vs. 3.86+/-0.44; p=.0005), independently of the high/low-estrogen dose. SI did not decrease during vaginal ring use (4.64+/-1.03 vs. 5.25+/-1.36; p=.57; p=.019 vs. oral). Total cholesterol and HDL cholesterol increased (p=.02) during OCs, independently of the dose. Triglycerides increased during both oral (p=.01) and vaginal (p=.032) contraceptive use. The present data indicate that in contrast to OC use, vaginal contraception with the ring does not deteriorate SI. The vaginal ring may represent an appropriate choice for long-term contraception in women at risk for developing diabetes mellitus or metabolic syndrome.
Hubacher D et al., 2009 Contraception Open Access
The copper intrauterine device (IUD) can cause side effects in some women; increased uterine bleeding and pain may cause early removal. Because of simplified reporting from previous research, little is known about how side effects might change over time. This is a secondary analysis of a prospective study of 1947 first-time copper IUD users. Over a 1-year period, we collected detailed information on side effects and looked for trends using generalized mixed-effects regression modeling. During menses, most bleeding and pain side effects were found to decrease over time (p<.05). During intermenstrual intervals, overall spotting and pain complaints remained unchanged, but the number of days with these problems increased (p<.05). Serious side effects that prompted either a clinic visit or IUD removal had varied patterns over time, depending on the type of problem. Side effects from the copper IUD can be troubling for both user and clinician. Some problems improve over time, while others do not. This information may be helpful in counseling women who are considering IUD use and current users who are contemplating IUD removal due to side effects.
Bernier MO et al., 2009 Arthritis Rheum
To assess whether the risk of incident systemic lupus erythematosus (SLE) is associated with the use of combined oral contraceptives (COCs), because studies of the link between exogenous hormonal exposure and the risk of SLE have produced conflicting results. We conducted a population-based nested case-control study among women ages 18-45 years, using the UK's General Practice Research Database. All incident cases of SLE from 1994-2004 (n = 786) were identified in the database and matched with up to 10 controls (n = 7,817) among women without SLE at the time of the case's diagnosis. The adjusted rate ratio (RR) of incident SLE associated with any use of COC was 1.19 (95% confidence interval [95% CI] 0.98-1.45), whereas with current use it was 1.54 (95% CI 1.15-2.07). The rate was particularly increased in current users who had only recently started COC use (RR 2.52, 95% CI 1.14-5.57) compared with longer-term current users (RR 1.45, 95% CI 1.06-1.99). The risk appeared to be particularly elevated with current exposure to firstor second-generation contraceptives (RR 1.65, 95% CI 1.20-2.26), and increasing with the dose of ethinyl estradiol (RR 1.42, 1.63, and 2.92 for < or =30 microg, 31-49 microg, and 50 microg, respectively). The use of COCs is associated with an increased risk of SLE. This risk is particularly elevated in women who recently started contraceptive use, suggesting an acute effect in a small subgroup of susceptible women.
Roberts SC et al., 2008 Proceedings. Biological sciences
Previous studies in animals and humans show that genes in the major histocompatibility complex (MHC) influence individual odours and that females often prefer odour of MHC-dissimilar males, perhaps to increase offspring heterozygosity or reduce inbreeding. Women using oral hormonal contraceptives have been reported to have the opposite preference, raising the possibility that oral contraceptives alter female preference towards MHC similarity, with possible fertility costs. Here we test directly whether contraceptive pill use alters odour preferences using a longitudinal design in which women were tested before and after initiating pill use; a control group of non-users were tested with a comparable interval between test sessions. In contrast to some previous studies, there was no significant difference in ratings between odours of MHC-dissimilar and MHC-similar men among women during the follicular cycle phase. However, single women preferred odours of MHC-similar men, while women in relationships preferred odours of MHC-dissimilar men, a result consistent with studies in other species, suggesting that paired females may seek to improve offspring quality through extra-pair partnerships. Across tests, we found a significant preference shift towards MHC similarity associated with pill use, which was not evident in the control group. If odour plays a role in human mate choice, our results suggest that contraceptive pill use could disrupt disassortative mate preferences.
Rietzschel E et al., 2008 Circulation
Oral contraceptives (OC) are among the most frequently used drugs in the world with approximately 100 million women worldwide taking OC. In contrast to the active controversy surrounding hormone replacement therapy, little attention has been focused on OC, a drug therapy taken by far more women for far longer time periods. We describe the population effects of current and long-term OC exposure on a prognostically well validated marker of arterial stiffness: carotid-femoral pulse wave velocity (PWV). The Asklepios study is a representative sample (2524 apparently healthy M/F volunteers, aged 35–55 years, 1301 women) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened (biochemistry, lifestyle, cardiac and vascular echography, arterial tonometry). PWV was measured from flow patterns registered by Doppler echography in the femoral and carotid arteries. Of 1301 women (median age 45.7 y), 27.4% were actively taking OC. In contrast past use of OC is far more prevalent with 81% of women having taken OC for at least 1 year. The median duration of exposition in these women was 13 years. Age-adjusted PWV was higher in women currently taking OC: 6.75 versus 6.55 m/s (difference 0.19 ± 0.09 m/s; p = 0.034). However, current OC users also had higher blood pressures (BP): systolic BP (+4.4 ± 0.9 mmHg; p < 0.001), diastolic BP (+2.3 ± 0.6 mmHg; p < 0.001). After adjustement for BP, the difference in PWV between current OC users and non-users became non-significant: 6.60 versus 6.62 m/s (difference 0.02 ± 0.09 m/s; p = 0.814). In contrast, duration of OC use is a significant determinant of PWV, even after adjustement for age, BP, lipid levels, body size, heart rate, drug therapy (lipid-lowering, antihypertensive), glycemic status and smoking: F = 6.1; p = 0.013. Per 10 years of OC exposure PWV increased by 0.1 m/s (0.02– 0.18; p = 0.013). Use of OC is associated with increased vascular stiffness in women. Current use is associated with increased PWV because OC’s increase blood pressure, long-term use (probably through structural remodelling of the vessels) is an independent determinant of PWV, increasing PWV by 0.10 m/s per 10 years exposure.
Cornish JA et al., 2008 Am J Gastroenterol
Several environmental and genetic factors have been implicated to date in the development of Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to provide a quantification of the risk of oral contraceptive pill (OCP) use in the etiology of inflammatory bowel disease. A literature search was performed to identify comparative studies reporting on the association of oral contraceptive use in the etiology of UC and CD between 1983 and 2007. A random-effect meta-analysis was used to compare the incidence of UC or CD between the patients exposed to the OCP and nonexposed patients. The results were adjusted for smoking. A total of 75,815 patients were reported on by 14 studies, with 36,797 exposed to OCP and 39,018 nonexposed women. The pooled relative risk (RR) for CD for women currently taking the OCP was 1.51 (95% confidence interval [CI] 1.17-1.96, P= 0.002), and 1.46 (95% CI 1.26-1.70, P < 0.001), adjusted for smoking. The RR for UC in women currently taking the OCP was 1.53 (95% CI 1.21-1.94, P= 0.001), and 1.28 (95% CI 1.06-1.54, P= 0.011), adjusted for smoking. The RR for CD increased with the length of exposure to OCP. Moreover, although the RR did not reduce once the OCP was stopped, it was no longer significant once the OCP was stopped (CI contains 1), both for CD and for UC. This study provides evidence of an association between the use of oral contraceptive agents and development of IBD, in particular CD. The study also suggests that the risk for patients who stop using the OCP reverts to that of the nonexposed population.
Rietzschel E et al., 2007 Circulation
Combination therapy with the female hormones estrogen (E) and progestins are very frequently used with approximately 100 million women worldwide taking oral contraceptives (OC). Recent trials have cast doubt on the cardiovascular safety of hormonal replacement therapy (HRT). In contrast to the HRT-controversy, little attention has been focused on OC, a therapy using 10 –100 fold higher levels of E than HRT. We describe population correlates of long-term OC use. The Asklepios study is a representative sample (2524 M/F volunteers, 35–55 years) from the Belgian general population free from overt cardiovascular disease. Vascular echography of the carotid and femoral arteries was systematically performed and atherosclerosis was defined by presence of carotid or femoral plaque. Of 1301 women (median age 45.7 y), 27.4% were taking OC and 10.0% were taking HRT. In contrast, past OC-use is far more prevalent: 81% of women having taken OC for at least 1 year, with a median exposition of 13 years. After multivariate adjustment for age, smoking, blood pressure, lipids, obesity, diabetes, physical activity, fruit, vegetable and alcohol intake, educational level and drug therapy (lipid-lowering, antihypertensive, aspirin), use of OC was associated with a significant increase in carotid or femoral unilateral plaque. Odds ratio’s (OR) per 10 years of OC exposure were: carotid plaque 1.17 (1.00 –1.33) and femoral plaque 1.28 (1.10 –1.47). We also looked at prevalence of bilateral disease (involvement of right and left carotid/femoral artery) as a more stringent phenotype of atherosclerosis. OR per 10 years OC exposure were: carotid plaque 1.42 (1.03–1.84); femoral plaque 1.34 (1.05–1.63). Interpretation : Use of contraceptive therapy is very common and associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20 –30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread (>80% of our population sample; > 100 million women globally) and usually prolonged OC use (>10 years) these results suggest OC use could be an important factor in the global atherosclerotic burden.
Moreau C et al., 2007 Contraception
This study examines contraceptive discontinuation due to method dissatisfaction among women in the United States. The study population, drawn from the 2002 National Survey of Family Growth, consisted of 6724 women (15-44 years of age) who had ever used a reversible contraceptive method. We first estimated the overall proportion of women who had ever discontinued their contraceptive due to dissatisfaction. We then calculated method-specific discontinuation risks due to dissatisfaction and analyzed the reasons for dissatisfaction given by women who had ever stopped using Norplant, Depo-Provera, oral contraceptives or condoms. Overall, 46% of women had ever discontinued at least one method because they were unsatisfied with it. Dissatisfaction-related discontinuation risks varied widely by the diaphragm and cervical cap showed the highest proportions of such discontinuation (52%), followed by long-acting hormonal methods (42%). Oral contraceptives were associated with an intermediate risk of dissatisfaction-related discontinuation (29%), while condoms had the lowest risk (12%). A broader understanding of women's concerns and experiences using contraception could help health care providers redesign counseling strategies to improve contraceptive continuation.
Baeten JM et al., 2007 AIDS
Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive. To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population. Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases. : Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82). In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.
Young EA et al., 2007 Psychoneuroendocrinology Open Access
Hormone-based contraceptives affect mood in healthy women or in women with premenstrual dysphoric disorder (PMDD). No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen-progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD. This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the US, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen-progestin)(N=232), progestin-only (N=58), and no hormone treatment (N=948). Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder (COCD) comorbidity than either of the other groups. Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women.
Dinger JC et al., 2007 Contraception
The study was conducted to compare risks of adverse cardiovascular and other events associated with the use of drospirenone (DRSP)-containing oral contraceptives (OCs) and other OCs. The European Active Surveillance study (EURAS) was a multinational, prospective, noninterventional cohort study of new users of DRSP, levonorgestrel (LNG) and other progestin-containing OCs. Semiannual follow-up was based on mailed questionnaires, with additional follow-up procedures when needed. Overall, 58,674 women were followed for 142,475 women-years of observation. Loss to follow-up was 2.4%. Serious adverse and fatal events were rare, and rate ratios were close to unity (1.0). Cox regression analysis of cardiovascular outcomes yielded hazard ratios for DRSP-containing vs. LNG-containing and other OCs of 1.0 and 0.8 (upper 95% confidence limits, 1.8 and 1.3) for venous, and 0.3 and 0.3 (upper 95% confidence limits, 1.2 and 1.5) for arterial thromboembolism, respectively. Risks of adverse cardiovascular and other serious events in users of a DRSP-containing OC are similar to those associated with the use of other OCs.
Kleinschmidt I et al., 2007 Contraception
To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception. Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year. There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study. There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.
Morrison CS et al., 2007 AIDS
Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.
Myer L et al., 2007 Int J Epidemiol
Many women using hormonal contraceptives are also at risk of sexually transmitted HIV infection, but data are mixed on whether hormonal contraception increases women's risk of HIV. We investigated associations between HIV incidence and use of combined oral contraceptives (COC), norethindrone enanthate (NET-EN) or depot medroxyprogesterone acetate (DMPA) in a cohort of South African women. Participants were 4200 HIV-negative women aged 35-49 years enrolled into a cervical cancer screening trial. At enrollment, women were tested for sexually transmitted infections and reported on their sexual behaviour and contraceptive use. During the 24 months of follow-up, women reported on their sexual behaviours and contraceptive use and underwent repeat HIV testing. During the 5010 person-years of follow-up, 111 incident HIV infections were observed (HIV incidence, 2.2 infections/100 person-years). At enrollment, 21% of women reported using hormonal contraception, primarily DMPA (14% of all women) or NET-EN (5%). After adjusting for sexual risk behaviours and sexually transmitted infections, the incidence of HIV was similar among women using COC, NET-EN or DMPA compared with women not using any hormonal method [incidence rate ratios and 95% confidence intervals, 0.65, 0.16-2.66; 0.79, 0.31-2.02 and 0.96, 0.58-1.59, respectively]. There was also no association between increased duration of DMPA use and HIV incidence (P-value for trend, 0.51). These findings contribute to the evidence from general population cohorts of women that hormonal contraceptive use is not associated with increased risk of HIV acquisition. Nonetheless, family planning services are an important venue for HIV prevention activities.
Hubacher D et al., 2006 Hum Reprod
Increased menstrual bleeding and pain are the primary side effects that lead to early removal of the copper intrauterine device (IUD). Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) are proven treatments for such IUD-induced problems, but their effect on early IUD removal is unknown. A total of 2019 first-time IUD users were recruited in Chile for this double-blind, randomized, placebo-controlled trial. Half of the participants were given ibuprofen and instructions to take 1200 mg daily during menses (for up to 5 days each cycle) for the first 6 months of IUD use. The other half were asked to take an identical appearing placebo in the same manner. The primary outcome was IUD removal within 12 months of insertion. A total of 1011 and 1008 women were randomly assigned to ibuprofen and placebo, respectively. During 12 months of observation, 190 had the device removed because of dysmenorrhoea and/or increased menstrual bleeding: 85 in the placebo group and 105 in the ibuprofen group. For ibuprofen users, the hazard ratio for removal for these IUD-induced side effects was 1.0 and 1.2 at 6 and 12 months, respectively (both not significant). Although increased menstrual bleeding and pain are common reasons for early IUD removal, prophylactic use of ibuprofen, at the dosage used here, does not reduce removal rates.
Curtis KM et al., 2006 Contraception
This systematic review examines evidence evaluating whether women with headaches who use combined oral contraceptives (COCs) have a greater risk of stroke than women with headaches who do not use COCs. We searched MEDLINE for articles published from 1966 through March 2005 relevant to headaches and COC use as risk factors for stroke. Of the 79 articles identified, nine met our selection criteria (eight reports of six observational studies plus one meta-analysis). All studies reported specifically on migraine headaches. Evidence from six case-control studies suggested that COC users with a history of migraine were two to four times as likely to have an ischemic stroke as nonusers with a history of migraine. The odds ratios for ischemic stroke ranged from 6 to almost 14 for COC users with migraine compared with nonusers without migraine. The three studies that provided evidence on hemorrhagic stroke reported low or no risk associated with migraine or with COC use.
Kulkarni J et al., 2005 Aust Fam Physician
Although there have been numerous studies investigating the relationship between the use of oral contraceptives and depressive symptoms, they have differed widely in both their methods and findings. A particular problem is determining and quantifying depression. The authors onducted a pilot study using well validated depression rating scales. (non-author abstract)
Alonso A et al., 2005 Arch Neurol
Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS). To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. DESIGN AND A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners. One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records. The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity. The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS.
Hitchcock CL et al., 2004 Womens Health Issues
For many years, individual women and doctors have experimented with extending the duration of active oral contraceptive (OC) pills between pill-free intervals (long OC) to control menstruation. The U.S. approval of an OC with 84 active days and 7 pill-free days in 2003 has attracted considerable media attention. In this review we consider the published evidence on the effectiveness, side effects, and risks of menstrual suppression with long OC. We performed a systematic review of published literature on long OC, up to April 2003. Ten papers were located; two were randomized trials comparing long OC to standard OC; the remaining studies were single-group observational studies. Women on long OC schedules had fewer days of scheduled bleeding during days without pills but more days of unscheduled bleeding and spotting than those on standard OC. These problems were worse for women new to OC and diminished over time. Women on long OC were more likely to discontinue due to poor control of bleeding; women on standard OC were more likely to stop because of problems with headaches. Women on long OC and standard OC both showed increases in physiological factors related to clotting, with a nonsignificant tendency for those on long OC to be more affected. No studies considered the effects of long OC on breast tissue, breast density, endometrial safety, or adolescent maturation and reproductive development. No systematic data were available on the return to reproductive function and fertility after taking long OC. There were no placebo-controlled trials and no information on how long OC compares to normal, unmedicated menstrual cycles. Therefore we believe scientific evidence for safety of long OC use is presently lacking.
Burkman R et al., 2004 Am J Obstet Gynecol
Since the introduction of hormonal contraceptives in the 1960s, there have been a variety of both health benefits and safety concerns attributed to their use. In most instances, the noncontraceptive benefits of oral contraceptives (OCs) outweigh the potential cardiovascular risks. In fact, the probability of a patient experiencing a cardiovascular event while taking a low-dose OC is very low. However, smoking, hypertension, obesity, and diabetes are risk factors that must be taken into account when prescribing OCs. The neoplastic effects of hormonal contraceptives have been extensively studied, and recent meta-analyses indicate that there is a reduction in the risk of endometrial and ovarian cancer, a possible small increase in the risk for breast and cervical cancer, and an increased risk of liver cancer. Finally, many women will experience noncontraceptive health benefits with OCs that expand far beyond pregnancy prevention. Some of these benefits include reduction in menstrual-related symptoms, fewer ectopic pregnancies, a possible increase in bone density, and possible protection against pelvic inflammatory disease.
Backman T et al., 2004 American journal of obstetrics and gynecology
This study was undertaken to evaluate the pregnancy rate with the levonorgestrel intrauterine system (LNG IUS) and to analyze the outcome of pregnancies with the LNG IUS in situ in regular use. Questionnaires from 17,360 users of the LNG IUS were analyzed. With the consent of women reporting pregnancy during the use of the LNG IUS, related hospital records were reviewed concerning the pregnancies. Originally 132 pregnancies were reported. Medical records were reviewed from 108 of these women. In 64 pregnancies, conception occurred with the LNG IUS in situ. Thirty-three pregnancies were ectopic. The 5-year cumulative pregnancy rate per 100 users was 0.5 and the 5-year Pearl rate was 0.11. Pregnancy with the LNG IUS in situ is rare. Ectopic pregnancies constitute 53% of all pregnancies. Typical pregnancy symptoms occur during pregnancies with the LNG IUS. The importance to counsel about the risk of pregnancy before insertion is emphasized.
Lebrun CM et al., 2003 Br J Sports Med Open Access
Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear. To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes. This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO(2)MAX) >/==" BORDER="0">50 ml/kg/min. Four measures of athletic performance were tested: VO(2)MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO(2)MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase). Absolute and relative changes in VO(2)MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO(2)MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment. The decrease in VO(2)MAX that occurs when oral contraceptive is taken may influence elite sporting performance in some women. Further studies are required to determine the mechanisms of this change.
Rauchfuss M et al., 2003 Contraception
A discrepancy exists between the interest in modern methods of natural family planning (NFP) and their actual use in developed countries. To explore reasons for this discrepancy, we analyzed data from a questionnaire administered to postpartum women in Berlin (n = 223) and Cracow (n = 233). Knowledge of NFP, past use of NFP and expected effects of abstinence on the partnership were independently associated with interest in using NFP, but not the choice to do so among those interested. Desire for future pregnancies, importance of religious belief and location in Cracow were independently associated with the choice to use NFP among those interested. Perceived accuracy of observation to identify the fertile time and acceptance of own body were independently associated with both interest in and choice to use NFP. Frequency of intercourse had no effect on interest. These results suggest that increased access and cultural support would likely lead to a higher prevalence of NFP use in developed countries.
Kiddugavu M et al., 2003 AIDS
Hormonal contraceptives have been associated with increased risk of HIV acquisition. The association between hormonal contraception use and HIV acquisition was assessed in a rural community-based cohort in Rakai District, Uganda. A group of 5117 sexually active HIV-negative women were surveyed at 10 month intervals between 1994 and 1999. Information on demographic and sociobehavioral characteristics, use of hormonal contraception (pill and injectable methods), condoms and the number of sexual partners was obtained by home-based interview. HIV incidence rate ratios (IRR) and 95% confidence intervals (CI) associated with hormonal contraception were estimated by multivariate Poisson regression after adjustment for age, condom use, number of sexual partners, marital status, education and history of genital ulcer disease. At one or more interviews, 16.6% of women reported use of hormonal contraceptives and 23.0% reported condom use. HIV incidence was 2.3/100 person-years in hormonal contraceptive users compared with 1.5/100 person-years in non-hormonal contraceptive users (unadjusted IRR, 1.56; 95% CI, 1.00-2.33). After multivariate adjustment, the IRR associated with hormonal contraceptives was reduced to 0.94 (95% CI, 0.53-1.64). The adjusted IRR was 1.12 (95% CI, 0.48-2.56) with oral contraceptive use and 0.84 (95%CI, 0.41-1.72) with injectable methods. Use of hormonal contraception is not associated with HIV acquisition after adjustment for behavioral confounding.
Lussana F et al., 2003 Thrombosis research
To compare the levels of total homocysteine (tHcy), folate, vitamin B6 and B12, in women not using oral contraceptives (OC) vs. those using OC. 219 healthy women were enrolled in the study; 159 of them had not been using OC for at least 12 months prior to their enrollment, while 60 were on regular OC treatment. The median levels of vitamin B6 and B12 were significantly lower in OC users than in non-users (24.2 vs. 32.9 nmol/l, p=0.029; 278 vs. 429 ng/ml, p<0.001). There were no statistically significant differences in the levels of tHcy (fasting and post-methionine loading) and folate. In our cross-sectional study, OC use was associated with low vitamin B6 and B12 levels. Since low vitamin B6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users.
Stanford JB et al., 2002 Am J Obstet Gynecol
There are many potential mechanisms of action for the intrauterine device (IUD), which vary by type of IUD (inert, copper, or hormonal). This paper reviews the evidence for each potential mechanism of action. On the basis of available data for fertilization rates and clinical pregnancy rates, the relative contribution of mechanisms acting before or after fertilization were quantitatively estimated. These estimates indicate that, although prefertilization effects are more prominent for the copper IUD, both prefertilization and postfertilization mechanisms of action contribute significantly to the effectiveness of all types of intrauterine devices.
Lidegaard Ø et al., 2002 Contraception
The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994-1995 and 1200 per year 1996-1998. Response rates for cases and controls were 87.2% and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis or myocardial infarction, coagulopathies, diabetes, years of schooling, and previous birth. The risk of VTE among current users of OCs was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: <1 year, 7.0 (5.1-9.6); 1-5 years, 3.6 (2.7-4.8); and >5 years, 3.1 (2.5-3.8), all compared with nonusers of OCs. After adjustment for confounders, current use of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins when compared with nonuse resulted in ORs for VTE of 2.9 (2.2-3.8) and 4.0 (3.2-4.9), respectively. After adjusting for progestin types and length of use, the risk decreased significantly with decreasing estrogen dose. With 30-40 microg as reference, 20 and 50 microg products implied ORs of 0.6 (0.4-0.9) and 1.6 (0.9-2.8), respectively (p(trend) = 0.02). After correction for duration of use and differences in estrogen dose, the third/second-generation risk ratio was 1.3 (1.0-1.8; p <0.05). In conclusion, use of OCs was associated significantly to the risk of VTE. The risk among current users was reduced by more than 50% during the first years of use. The risk increased more than 100% with increasing estrogen dose, and the difference in risk between users of thirdand second-generation OCs, after correction for length of use and estrogen dose, was 33%.
den Tonkelaar D et al., 2002 Eur J Contracept Reprod Health Care
To study the extent to which variation in satisfaction with a birth control method is explained by variation in perceived physical and psychological effects. A population survey among 1466 German women was carried out. Within the overall sample, 1303 women had ever used oral contraceptives, 996 had relied on condoms, 342 had ever used intrauterine devices (IUD), 428 had used natural family planning and 139 women were sterilized. For each method a woman had ever used, she answered questions about satisfaction with the method, concerns about getting pregnant or suffering health risks during use, ease of use, changes in sexual relationship, relationship with the partner and mood. Past and current users of oral contraceptives and IUDs and sterilized women additionally reported changes in menstrual bleeding. Variation in satisfaction was, for a large part, explained by variation in health concerns among oral contraceptive users, by variation in perceived changes in the quality of the sexual relationship among condom users, by perceived ease of use among IUD users and sterilized women, and by variation in pregnancy concern among natural family planning users. Counselling about these perceived experiences is most likely to result in greater satisfaction and therefore improved compliance.
Brown C et al., 2002 J Reprod Med
To determine whether a new monophasic oral contraceptive containing drospirenone/ethinyl estradiol reduces premenstrual symptoms. In an open-label study measuring intrasubject changes in premenstrual symptoms and comparing effects between women who were new users of oral contraceptives and those who switched from previous contraceptives, ethinyl estradiol (30 micrograms) and drospirenone (3 mg) were administered for 13 menstrual cycles to 326 healthy women aged 18-35 years. Subjects completed the 23-item Women's Health Assessment Questionnaire at baseline and at the end of the sixth cycle. At the end of cycle 6, premenstrual and menstrual symptom scores on the negative affect and water retention scales were reduced significantly relative to baseline, as was increased appetite during the premenstrual and menstrual phases. Similar improvements were seen among new users of hormonal contraceptives and those who switched from previous contraceptives. Impaired concentration scale scores were not significantly reduced from baseline, and assessments of undesired hair changes and feelings of well-being did not change appreciably. An oral contraceptive containing drospirenone/ethinyl estradiol may reduce the premenstrual symptoms of negative affect, water retention and increased appetite.
Hernán MA et al., 2000 Neurology
Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS. We assessed whether MS incidence was associated with oral contraceptive use or parity in two cohort studies of U.S. women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55 years at baseline in 1976) and the Nurses' Health Study II (NHS II; 116,671 women aged 25 to 42 years at baseline in 1989). Participants with a diagnosis of MS before baseline were excluded. Oral contraceptive history and parity were assessed at baseline and updated biennially. During follow-ups of 18 years (NHS) and 8 years (NHS II) we documented a total of 315 definite or probable cases of MS. Neither use of oral contraceptives nor parity were significantly associated with the risk of MS. As compared with women who never used oral contraceptives, the age-adjusted relative risk (95% CI) was 1.2 (0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users. Similar results were obtained after adjustment for latitude, ancestry, and other potential confounding factors. There was no clear trend of MS risk with either increasing duration of use or time elapsed since last use. Age at first birth was also not associated with the risk of MS. These prospective results do not support a lasting protective effect of oral contraceptive use or pregnancy on the risk of MS. The decision to use hormonal contraception should not be affected by its effects on the risk of MS.
Parkin L et al., 2000 Lancet
In a national case-control study of fatal pulmonary embolism in New Zealand women of childbearing age, we estimated that current users of combined oral contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national distribution data, the absolute risk of death from pulmonary embolism in current users was estimated to be 10.5 per million woman-years.
Oddens BJ, 1999 Contraception
User satisfaction and the physical and psychological effects of five commonly used contraceptive methods were investigated in a population survey among 1466 West German women. The focus was on effects attributed by current and past users to these methods, rather than objectively assessed effects, to shed further light on personal experiences that are highly relevant to the user but often remain unknown to prescribers and unreported in the medical literature. Within the overall sample, 1303 women were surveyed concerning their current or past use of oral contraceptives (OC), 996 regarding condoms, 342 with respect to intrauterine devices (IUD), 428 in regard to natural family planning (NFP), and 139 in relation to sterilization (respondents completed questions about each method used). It emerged that satisfaction was greatest with sterilization (92% of users), followed by OC (68% of ever users), IUD (59%), NFP (43%), and condoms (30%). Almost one in three NFP users had experienced an unwanted pregnancy during use of this method, as compared with one in 20 OC and condom users. The majority of users reported no mood changes during use of the methods studied. The percentages reporting negative mood changes (various items were scored) were up to 16% among OC users, 23% among condom users, and 30% among NFP users. The latter observations suggested that subjective side effects of a contraceptive agent on mood generally reflected, at least in part, the user's sense of confidence in the method concerned (notably, with regard to efficacy and safety). Oral contraceptives, IUD, and sterilization had a broadly positive impact on sex life, whereas that of condoms was often negative. Whereas OC users often reported less heavy and painful menstruation (in up to 56% of cases), IUD were associated with heavier, prolonged, and more painful menstruation (in up to 65% of cases), as also was sterilization, although to a lesser extent (in up to 32% of cases). Overall, the study findings indicated that OC and sterilization had less negative impact on physical and psychological functioning than the other methods studied, in contrast to what the general public often believes.
Trussell J et al., 1999 Fam Plann Perspect
The incidence of unintended pregnancy has long been used as a primary indicator of the state of reproductive health. However, the definition--and therefore the measurement--of this indicator has been elusive. Data from the 1995 National Survey of Family Growth (NSFG) were used to compare levels of unintended pregnancy among contraceptive users based on two definitions--the standard definition based on women's reports of contraceptive failure, and the NSFG definition based on pregnancy timing (wanted then, wanted later, or not wanted then or in the future). An attitudinal scale was used to examine women's feelings about their unintended pregnancy. Of pregnancies classified as contraceptive failures under the standard definition, only 68% were unintended pregnancies--94% of those ending in abortion and 60% of those ending in birth. Just 59% of women with a contraceptive failure classified as an unintended pregnancy reported feeling unhappy or very unhappy about their pregnancy, while 90% of those with a failure classified as an intended pregnancy reported being happy or very happy. Measures of wantedness based on women's feelings about their pregnancy may correlate more closely with important pregnancy outcomes than do traditional measures of intendedness. This study examines the alternative implications of the measurements of unintended pregnancy during contraceptive failure in the US. The data from the 1995 National Survey of Family Growth (NSFG) were used to compare levels of unintended pregnancy among contraceptive users based on two definitions: the standard definition based on women's report of contraceptive failure; and the NSFG definition based on pregnancy timing. An attitudinal scale was used to examine women's feeling about their unintended pregnancy. The results of the analysis revealed 68% were unintended pregnancies under the classification of standard definition, while 59% of women with contraceptive failure classified under NSFG definition and reported feeling unhappy or very unhappy about their pregnancy. About 90% of those with contraceptive failure classified as an intended pregnancy reported feeling happy or very happy. Although these results were consistent with one another, it is still unclear why these women feeling happy about their unintended pregnancy are practicing contraception.
Hillis SD et al., 1999 Obstetrics and gynecology
To evaluate the cumulative probability of regret after tubal sterilization, and to identify risk factors for regret that are identifiable before sterilization. We used a prospective, multicenter cohort study to evaluate the cumulative probability of regret within 14 years after tubal sterilization. Participants included 11,232 women aged 18-44 years who had tubal sterilizations between 1978 and 1987. Actuarial life tables and Cox proportional hazards models were used to identify those groups at greatest risk of experiencing regret. The cumulative probability of expressing regret during a follow-up interview within 14 years after tubal sterilization was 20.3% for women aged 30 or younger at the time of sterilization and 5.9% for women over age 30 at sterilization (adjusted relative risk [RR] 1.9; 95% confidence interval [CI] 1.6, 2.3). For the former group, the cumulative probability of regret was similar for women sterilized during the postpartum period (after cesarean, 20.3%, 95% CI 14.5, 26.0; after vaginal delivery, 23.7%, 95% CI 17.6, 29.8) and for women sterilized within 1 year after the birth of their youngest child (22.3%, 95% CI 16.4, 28.2). For women aged 30 or younger at sterilization, the cumulative probability of regret decreased as time since the birth of the youngest child increased (2-3 years, 16.2%, 95% CI 11.4, 21.0; 4-7 years, 11.3%, 95% CI 7.8, 14.8; 8 or more years, 8.3%, 95% CI 5.1, 11.4) and was lowest among women who had no previous births (6.3%, 95% CI 3.1, 9.4). Although most women expressed no regret after tubal sterilization, women 30 years of age and younger at the time of sterilization had an increased probability of expressing regret during follow-up interviews within 14 years after the procedure.
Lewis MA et al., 1999 Hum Reprod
Previous discussions have indicated that the small increases of risk of venous thromboembolism (VTE) associated with newer combined oral contraceptives (third generation, containing desogestrel and gestodene) may be attributed to bias due to cohort effects. In a case-control analysis, this may produce an overestimate of risk of newer preparations. In 10 centres in Germany and the UK, the Transnational Study analysed data from 502 women aged 16-44 years with VTE, and from 1864 controls matched for 5-year age group and region. Information on lifetime exposure history from all subjects was added to the dataset used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17 622 continuous exposure episodes comprising 47 914 person-years of observation, the adjusted hazard ratio (equivalent to odds ratio, OR) of VTE for the comparison of current users of third-generation versus current users of second-generation (primarily levonorgestrel compounds) combined oral contraceptives was 0.8 (0.5 to 1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1 to 2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the Transnational Study data show no evidence for an increased risk of VTE with thirdcompared with second-generation combined oral contraceptives.
Todd J et al., 1999 Hum Reprod
In October 1995 the Committee on Safety of Medicines advised UK doctors and pharmacists that oral contraceptives containing desogestrel and gestodene were associated with double the risk of venous thromboembolic events (VTE) compared to pills containing other progestogens. In 1997 data was analysed from the MediPlus database of UK general practitioner records, which reported odds ratios for desogestrel and gestodene lower than that for levonorgestrel. Here the results of a more stringent nested case control analysis on the MediPlus database are reported. The study was larger and cases were verified. A crude incidence of idiopathic VTE was found amongst users of combined oral contraceptives of 4.6 per 10 000 exposed women years. Using levonorgestrel 150 microg + ethinyloestradiol 30 microg as reference, non-significant odds ratios of 1.1 (0.5-2.6) for desogestrel 150 microg + ethinyloestradiol 30 microg and 1.1 (0.5-2.4) for gestodene 75 microg + ethinyloestradiol 30 microg were found. The results of this study show no significant difference in risk between different formulations of combined oral contraceptive.
Bloemenkamp KW et al., 1999 Arch Intern Med
The magnitude of the relative risk of venous thrombosis caused by low-dose oral contraceptive use is still debated because previous studies might have been affected by diagnostic suspicion and referral bias. We conducted a case-control study in which the effect of diagnostic suspicion and referral bias was excluded. The study was performed in 2 diagnostic centers to which patients with clinically suspected deep vein thrombosis of the leg were referred. History of oral contraceptive use was obtained before objective testing for thrombosis. Young females with an objective diagnosis of deep vein thrombosis were considered case patients, and those who were referred with the same clinical suspicion but who had no thrombosis served as control subjects. Participants were seen between September 1, 1982, and October 18, 1995: 185 consecutive patients and 591 controls aged 15 to 49 years with a first episode of venous thrombosis and without malignant neoplasms, pregnancy, or known inherited clotting defects. The overall odds ratio for oral contraceptive use was 3.2 (95% confidence interval [CI], 2.3-4.5); after adjustment for age, family history of venous thrombosis, calendar time, and center, the odds ratio was 3.9 (95% CI, 2.6-5.7). In the idiopathic group (120 patients and 413 controls, excluding recent surgery, trauma, or immobilization), the odds ratio for oral contraceptive use was 3.8 (95% CI, 2.5-5.9); after adjustment, the odds ratio was 5.0 (95% CI, 3.1-8.2). In this study, in which patients and controls were subj ect to the same referral and diagnostic procedures, we found similar relative risk estimates for oral contraceptive use as in previous studies. We conclude that diagnostic suspicion and referral bias did not play an important role in previous studies and that the risk of venous thrombosis with use of current brands of oral contraceptives still exists.
Thorogood M et al., 1999 Br J Obstet Gynaecol
To examine the risk of multiple sclerosis in users of combined oral contraceptives. Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners General practices throughout the United Kingdom. Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives.
AAPLOG, 1999
The mechanism of action of contraceptive drugs and devices forms an essential part of informed consent for patients considering various methods of family planning. Currently the literature is confusing at best, in part due to non-uniform definitions of basic terms, as well as the misinterpretation of endpoints of current. AAPLOG members take different positions on the issue of contraception per se. The purpose of this document is to investigate and summarize the current evidence-based concerns regarding potential embryocidal mechanisms of action of modern contraceptive drugs and devices. There are three reasons for concern about embryos conceived during the use of a particular contraceptive drug or device: 1. 1) All contraceptive drugs and devices “fail” at a certain rate. As noted in a recent paper, “Unintended pregnancies occur with all contraceptive methods, including IUDs. This provides incontrovertible evidence that fertilization and implantation can occur, albeit rarely, with modern methods of contraception.”1 2. 2) Since pregnancies can and do occur during the use of all contraceptive drugs and devices, then we know by definition that fertilization, which marks the beginning of an embryonic human organism, can and does happen with all contraceptive drugs and devices since by definition, an embryo must be created for pregnancy to occur. That means embryos are created at a certain rate with all contraceptive drugs or devices. 3. 3) The contraceptive drug or device will create a certain environment for the embryos created during their use. This environment may adversely affect embryo survival up to the point of yielding a positive pregnancy test at the end of the cycle (the contraceptive efficacy end point). The remainder of this article will try to summarize what is known in the published medical literature about the environment facing an embryo who has been created during the use of various kinds of contraceptive drugs or devices.
Lemaire JC et al., 1998 J Fam Pract
In the United States, approximately 4% of women of reproductive age use natural family planning (NFP) to avoid pregnancy. It is unclear whether this low number is related to a lack of available information, women's lack of interest, or other factors. Our study examined women's interest in using NFP either to become pregnant or to avoid it. A questionnaire was mailed to 1500 women, aged 18 to 50, who were randomly selected from driver's license renewal records in Missouri for the year beginning July 1991 and ending June 1992. Of the 747 returned questionnaires, 484 were from women who were still potentially fertile. Of these women, 22.5% indicated that they would be likely or very likely to use NFP in the future to avoid pregnancy, and 37.4% indicated that they would be likely or very likely to use NFP in the future to become pregnant. Only 2.8% were currently using a method of NFP. Past use of any method of NFP (including the outdated calendar rhythm method) to avoid pregnancy was associated with interest in future use of modern methods of NFP to avoid pregnancy. Past use of NFP to become pregnant and the possible desire for future pregnancy were associated with interest in future use of NFP to conceive. Many women who are not currently using NFP indicated that they are interested in doing so in the future, either to avoid pregnancy or to conceive. Interest in future use of NFP is associated with, but not limited to, those who have previously used NFP.
Bonnar J et al., 1997 Adv Contracept
A pilot study was conducted in Ireland to test the effectiveness of the calendar method of contraception. A conservative rule was used, requiring on average 16 days of abstinence per cycle. Among the 19 couples who entered into the study and were followed for up to seven cycles, there were no pregnancies. Since the length of abstinence was relatively long, we collected data to determine how couples expressed love and affection towards each other during those days when the woman was potentially fertile. We also collected data about barrier method use during the fertile time. We found that almost all couples gave each other hugs and kisses to show affection although couples were taught to abstain from vaginal intercourse during the fertile time. About one-third of the couples avoided genital contact, while about half reported using oral sex and/or frottage (body rubbing). Twice as many men reported using masturbation compared to women, although about half of the couples practiced mutual (partner) masturbation. In addition, about one-fifth of the couples used condoms during the fertile time in some cycles. These findings show that a variety of sexual expressions are used by couples when vaginal intercourse is to be avoided. Knowledge about these alternative sexual expressions may be important for couples who wish to engage in sexual activity and to avoid pregnancy.
Sanchez-Guerrero J et al., 1997 Arthritis Rheum
To examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE). Prospective cohort study of 121,645 women who were followed up every 2 years between 1976 and 1990 as part of the Nurses' Health Study. Women were classified as never users or past users of OCs based on self-report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (> or = 4 ACR criteria), 2) > or = 4 ACR criteria and any physician's diagnosis, 3) > or = 4 ACR criteria and diagnosis by an ACR-certified rheumatologist, 4) > or = 3 ACR criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR criteria. Compared with never users of OCs, and after adjusting for age and ever use of postmenopausal hormones, the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (> or = 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58), the relative risk for past users compared with never users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE. Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.
Farmer RD et al., 1997 Lancet
Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. Findings: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. Interpretation: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.
Reinberg AE et al., 1996 Chronobiology international
Sixteen healthy women users and nonusers of oral contraceptives (OC) volunteered to document a set of circadian rhythms. Nine were taking OC providing ethynyl estradiol (0.03-0.05 mg/24h, 21 days/month) combined with DL- or L-norgestrel or norethisterone. There was no group difference (p > 0.05) in median age (22 years), weight (57 kg), and height (162) cm). Data were obtained at fixed hours, 5 times/24h, during a 48-h span, in November. (Day activity from approximately 08:00 to approximately 23:00 h and night rest). Environmental conditions were controlled, using air-conditioned rooms of constant temperature (26 degrees +/- 0.5) and relative humidity 45% +/- 1. Both cosinor and ANOVA were used for statistical analyses. All circadian rhythms were validated with one exception: that of salivary melatonin was not detected in OC users. The 24h mean (M) exhibited group differences for certain variables: M was greater in OC than non-OC users for systolic blood pressure (p < 0.0001), heart rate (p < 0.01), skin blood flow (p < 0.04), and transepidermal water loss (p < 0.02). M was lower in OC than non-OC users in salivary cortisol (p < 0.04) and skin amino acids (p < 0.003). No group difference was detected in any other documented rhythms: diastolic blood pressure, grip strength of both hands, oral temperature, self-rated fatigue, and the skin variables of urea, lactate, triglycerides, and acid phosphatase activity.
Spitzer WO et al., 1996 BMJ Open Access
To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism. Matched case-control study. 10 centres in Germany and United Kingdom. Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting. Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year. Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.
No Authors Listed, 1995 Lancet
A multinational hospital-based case-control study of the risk of venous thromboembolic disease associated with combined oral contraceptives (OCs) done in 1989-93 prompted a separate inquiry comparing the risk of venous thromboembolism (VTE) associated with low oestrogen (< 35 micrograms ethinyloestradiol) OCs containing levonorgestrel with risks in low oestrogen preparations containing the third-generation progestagens desogestrel or gestodene. This analysis of data from 9 countries, involved 769 cases and 1979 age matched hospital controls and, in one centre, 246 community controls matched on age and general practice. 137 cases and 203 controls were current users of levonorgestrel (odds ratio [OR with 95% confidence interval] 3.5 [2.6-4.7]), with non-users as the reference; 35 cases and 28 controls were current users of desogestrel (9.1 [4.9-17.0]), and 36 cases and 28 controls were current users of gestodene (9.1 [4.9-16.7]). The ratios of these risks, compared with levonorgestrel, were 2.6 (1.4-4.8) for both products separately. Risk estimates adjusted for body mass index (BMI) were 3.4, 7.3, and 10.2 for levonorgestrel, desogestrel, and gestodene, respectively, compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene, respectively, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls exposed to desogestrel or gestodene were from the UK (Oxford region). In this centre risk estimates compared with non-users, adjusted for BMI, were 2.6, 5.3, and 5.7 for levonorgestrel, desogestrel, and gestodene, respectively. Current users of low oestrogen dose combined OCs containing desogestrel or gestodene appear to be at higher risk of VTE than users of combined OCs containing levonorgestrel. The possibility that these unexpected results on a secondary study objective are due to chance, bias, or residual confounding cannot be excluded entirely and the results need to be confirmed by independent studies. They are at variance with the apparently more favourable metabolic effects of the newer progestagens. Whether the new progestagens are associated with lower risk of arterial disease (stroke and myocardial infarction) must be evaluated further.
Bloemenkamp KW et al., 1995 Lancet
Recent concern about the safety of combined oral contraceptives (OCs) with third-generation progestagens prompted an examination of data from a population-based case-control study (Leiden Thrombophilia Study). We compared the risk of deep-vein thrombosis (DVT) during use of the newest OCs, containing a third-generation progestagen, with the risk of "older" products. We also investigated the influence of family history of thrombosis, previous pregnancy, age, and the thrombogenic factor V Leiden mutation. We selected 126 women with DVT and 159 controls aged 15-49 (mean age 34.9) and premenopausal and found, as compared with non-users, the highest age-adjusted relative risks to be that for an OC containing desogestrel and 30 micrograms ethinyloestradiol (relative risk [RR] 8.7, 95% CI 3.9-19.3). We found lower relative risks for all other types of OC, ranging from 2.2 to 3.8. In a direct comparison, users of the desogestrel-containing oral contraceptive had a 2.5-fold higher risk (95% CI 1.2-5.2) than users of all other OC types combined. The relative risk for the desogestrel-containing OC was similar among women with and without a family history--ie, preferential prescription because of family history cannot explain our findings. Nor could the excess risk be explained by previous pregnancy, and it was highest in the youngest age categories, where we would expect most new users. The age-adjusted RR for the desogestrel-containing contraceptive was 9.2 (3.9-21.4) among non-carriers of the factor V Leiden mutation and 6.0 (1.9-19.0) among carriers of the mutation. This latter risk is superimposed on the 8-fold increased risk of venous thrombosis for carriers of the factor V Leiden mutation. The risk of carriers using the desogestrel-containing OC as compared with noncarrier non-users will therefore be increased almost 50-fold. Use of low-dose OCs with a third-generation progestagen carries a higher risk of DVT than the previous generation of OCs. The absolute risk of DVT associated with these OCs seems to be especially high among carriers of the factor V Leiden mutation and among women with a family history of thrombosis. However, the higher risk associated with OC with a third-generation progestagen compared with previous generations was also present in women without factor V Leiden and with no family history.
No Authors Listed, 1995 Lancet
The composition and use of oral contraceptives (OCs) have changed since their cardiovascular side-effects were established 20 years ago. This report describes the risk of idiopathic venous thromboembolic (VTE) events (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) in association with current use of combined OCs among 1143 cases aged 20-44 and 2998 age-matched controls, as evaluated in a hospital-based, case-control study in 21 centres in Africa, Asia, Europe, and Latin America. OC use was associated with an increased risk of VTE in Europe (odds ratio 4.15 [95% CI 3.09-5.57]) and in non-European ("developing") countries (3.25 [2.59-4.08]). Risk estimates were generally higher for DVT than for PE but no consistent trend by certainty of diagnosis (definite, probable, possible) was found. Increased risk was apparent within 4 months of starting OCs, was unaffected by duration of current episode of OC use, and had disappeared within 3 months of stopping OCs. Relative risk estimates of VTE associated with OC use were unaffected by age of user, by history of hypertension (excluding hypertension in pregnancy), or in any consistent way by smoking. However, in both groups of countries increased body mass index (BMI) was an independent risk factor for VTE, and OC-associated odds ratios were higher among those with a BMI above 25 kg/m2 than among those with smaller BMIs. OC-associated risk estimates were high among women in Europe with a history of hypertension in pregnancy. Odds ratios associated with the use of OCs containing a third-generation progestagen were higher than those observed with progestagens of the first (norethindrone type) and second (norgestrel group) generation. Odds ratios associated with first and second generation progestagens tended to be lower, though not significantly, when used in combination with low (< 50 micrograms oestrogen) rather than higher oestrogen doses. This study confirms an association between OC use and VTE in Europe and the developing countries, although overall risk estimates associated with use were lower than demonstrated in most previous studies of non-fatal idiopathic VTE.
Jick H et al., 1995 Lancet Open Access
Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.
Fehring RJ, 1995 Linacre Q
Perinatal health professionals are in key positions to either promote or dissuade the use of Natural Family Planning (NFP). The purpose of this article is to describe a survey conducted with perinatal physicians and nurses on their knowledge and professional use of NFP. Four hundred and fifty physicians and nurses (150 MDs and 300 RNs) were sent a questionnaire on the use of and knowledge of NFP. One hundred sixty-six (or 37%) returned the completed questionnaires. Fifty-two percent of the nurses who returned the questionnaires and 48% of the physicians indicated they were taught about NFP in basic (generic) medical or nursing school. The average lecture time spent on the subject in either nursing or medical school was less than one hour. The majority learned about NFP through self-education or on-the-job training. Only four (1 RN and 3 MDs) are certified to teach NFP. Fifty-three percent of the nurses and 44% of physicians would not advise the use of NFP to avoid pregnancy. The most frequent reasons given for not promoting the use of NFP to either avoid or achieve pregnancy were that it is not effective, not natural, too difficult to learn, better methods are available, and it only works for highly motivated educated women.
Godet PG et al., 1995 Gut Open Access
Numerous epidemiological studies have been performed to determine factors that might contribute to the development of inflammatory bowel disease. Although the role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis (UC) have been assessed, most studies were of small sample size and characterised by low statistical precision. A meta-analysis was performed to increase the statistical power and to investigate the association between the use of oral contraceptives and the development of CD and UC. The study was based on a search of a Medline database from 1975 to October 1993 and a review of reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. All studies specifically designed to evaluate this association were selected. The combined results of nine studies--two cohort studies (30,379 unexposed and 30,673 exposed patients) and seven case-control studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection criteria were evaluated. The pooled relative risk (adjusted for smoking) associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29 (0.94, 1.77) for UC. These results suggest modest associations between the use of oral contraceptives and the development of CD and UC. As these associations are weak, non-causal explanations for the findings cannot be eliminated.
Boyko EJ et al., 1994 Am J Epidemiol
Research on inflammatory bowel disease risk among oral contraceptive users has reached conflicting conclusions. This population-based case-control study evaluated the effects of oral contraceptive use on ulcerative colitis and Crohn's disease risk. Cases were women enrollees, aged 15-68 years, of Group Health Cooperative of Puget Sound (a prepaid health plan based in western Washington State) who had ulcerative colitis (n = 211) or Crohn's disease (n = 91). Age-matched controls were randomly selected from the health plan enrollment file. An in-person interview obtained information about lifetime contraceptive use. Conditional logistic regression analysis was used to estimate relative risks and 95% confidence intervals for disease. Women who reported oral contraceptive use within 6 months before disease onset were at increased risk for both diseases compared with never users (relative risk (RR) of ulcerative colitis = 2.0, 95% confidence interval (CI) 1.2-3.3; RR of Crohn's disease = 2.6, 95% CI 1.2-5.5). Women who had used oral contraceptives for more than 6 years had the highest risk of Crohn's disease (RR = 5.1, 95% CI 1.8-14.3). In contrast, increasing duration of use was not associated with increased risk of ulcerative colitis. Adjustment for race, smoking, income, or pregnancy history did not substantially alter these results. Higher ulcerative colitis risk tended to occur among users of high estrogen dose oral contraceptives, while Crohn's disease risk was similar regardless of estrogen potency.
Villard-Mackintosh L et al., 1993 Contraception
Data from the Oxford.FPA prospective study show that oral contraceptive use and pregnancy have no discernible effect on the risk of developing multiple sclerosis (MS). Women of parity 0-2 developed MS twice as often as women of parity 3 or more but the difference did not reach statistical significance. Smoking may be a risk factor for developing MS. A nested case-control analysis did not identify any associations between MS onset and preceding illnesses.
Hilgers TW, 1993 Linacre Q
Sandler RS et al., 1992 Epidemiology
We used rosters of the Crohn's and Colitis Foundation of America to identify potential cases and peer-nominated controls to explore the reported association between oral contraceptives and inflammatory bowel disease. Overall, women who used oral contraceptives were at increased risk of developing Crohn's disease (odds ratio = 1.49, 95% confidence interval (CI) = 0.99-2.26). The findings persisted after adjustment for age at symptom onset, decade of onset, education, marital status, and location of disease. There was an interaction with cigarette smoking; the risk associated with oral contraceptives was elevated in current smokers (odds ratio = 2.64, 95% CI = 1.22-5.75), but not in former smokers or never-smokers. The risk was not elevated for ulcerative colitis (odds ratio = 1.10, 95% CI = 0.65-1.85).
Jarrett ME et al., 1990 Nurse Pract
For those women who have not been contraceptively sterilized, midlife is a period of waning fertility. However, the occurrence of anovulatory menstrual cycles is unpredictable. Contraceptive methods also become increasingly contraindicated, both medically and physiologically. This article reviews the physiology of waning fertility and midlife contraceptive options, and discusses implications for helping women meet their contraceptive needs throughout the perimenopausal period.
Lashner BA et al., 1990 Gastroenterology
Previous epidemiological studies suggesting an association between oral contraceptive use and ulcerative colitis incidence have been weak and conflicting. To measure a possible association, 46 incident cases of ulcerative colitis patients, women aged 18-50 years, were compared with peer-nominated age-matched and sex-matched controls. There were no differences between case and control patients in demographic characteristics. There was no association between oral contraceptive use and ulcerative colitis (current use: odds ratio 0.70, 95% confidence interval 0.27-1.83; former use: odds ratio 1.14, confidence interval 0.41-3.15; current or former use: odds ratio 0.86, confidence interval 0.40-1.85). Stratifying by disease location (pancolitis or left-sided disease) also failed to identify an association. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and ulcerative colitis. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of 2.8 and higher. In this matched case-control study of incident cases and community controls, there was no association between oral contraceptive use and ulcerative colitis incidence. To date, there is no evidence suggesting that women predisposed to the development of ulcerative colitis should be advised to avoid oral contraceptive use.
Lashner BA et al., 1989 Gastroenterology
Previous epidemiologic studies have suggested a weak association between oral contraceptive use and Crohn's disease, specifically Crohn's colitis. To measure a possible etiologic association, 51 women with Crohn's disease who were 18-50 yr old were studied and compared with peer-nominated ageand sex-matched controls. There were no differences between cases and controls with respect to race, religion, marital status, and number of pregnancies. There was no association between oral contraceptive use and Crohn's disease incidence [current use: odds ratio (OR) 0.73, 95% confidence interval (CI) 0.34-1.59; former use: OR 1.80, CI 0.61-5.29; current or former use: OR 1.00, CI 0.46-2.16]. Stratifying by disease location also failed to identify an association. Cigarette smoking was significantly associated with Crohn's disease incidence. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and Crohn's disease. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of greater than or equal to 2.76. From this community-based matched case-control study, there was no association between oral contraceptive use and Crohn's disease, and women need not be advised to discontinue oral contraceptive use when a diagnosis of Crohn's disease is made.
Logan RF et al., 1989 Int J Epidemiol
Data from the Royal College of General Practitioners Oral Contraception Study have been examined to determine whether oral contraceptive use was associated with the development of Crohn's disease or ulcerative colitis. Over a 17 year period Crohn's disease developed in 42 women and ulcerative colitis in 78. The incidence of both diseases was greater in oral contraceptive users compared to non-users with the rate ratio for Crohn's disease being 1.7 (95% confidence limits, 0.88, 3.2) and for ulcerative colitis being 1.3 (95% confidence limits 0.82, 2.0). For both diseases incidence was unrelated to parity or social class, but women smoking at recruitment had a greater incidence of Crohn's disease (rate ratio 1.8, 95% confidence limits 0.93, 3.3) and a reduced incidence of ulcerative colitis (rate ratio 0.68, 95% confidence limits 0.41, 1.1). Although these results are based on small numbers and could be chance findings, they are consistent with other studies showing associations between oral contraceptive use, smoking and the development of Crohn's disease and ulcerative colitis.
World Health Organization, 1987 Fertil Steril
During the 13-cycle effectiveness phase of a five-center study of the ovulation method of natural family planning, there were substantial differences, particularly between the two developed and the three developing countries, in the stated degree of satisfaction with the frequency of intercourse (most couples were satisfied in Bangalore, Manila, and San Miguel, whereas one-third of the subjects and half of their partners would have preferred more frequent intercourse in Auckland and Dublin) and in expressed difficulties associated with abstinence (e.g., 62% had occasional difficulty in Auckland, 14% in Bangalore, 55% in Dublin, 28% in Manila, and 5% in San Miguel). Cumulative net probabilities of discontinuation due to pregnancy were 1.8%, 18.6%, and 54.7% for couples in whom the male partner's degree of satisfaction was described as "no difficulty," "occasional difficulty," and "always some difficulty," respectively.
Laing JE, 1987 Stud Fam Plann
This paper presents the main survey findings from a nationally representative sample of 607 users of periodic abstinence methods in the Philippines in 1984. The survey was conducted because of the widespread popularity of periodic abstinence in the Philippines and a lack of detailed knowledge about how the method is understood and practiced in the Philippines. Findings are presented on the prevalence of the different types of periodic abstinence methods, the nature of their use, knowledge about the various periodic abstinence methods, instruction received, perceived advantages and disadvantages, the husband's role, and the use-effectiveness of periodic abstinence both with and without backup methods. The implications of these findings for program management and for future research are also discussed.
Robert JA et al., 1986 Adv Contracept Deliv Syst
Human cervical mucus from women using Lippes Loop and T-Cu-200 IUDs was used to study sperm migration in vitro using flat capillary tubes. Cervical mucus from women bearing no IUD was used as the control. 100% of the control samples, 83% of the Lippes Loop users, and 88% of the T-Cu-200 users had more than 100 spermatozoa/field of 100x. In 17% and in 11% there were between 40 and 100 spermatozoa/field of 100x in the Lippes Loop and T-Cu-200 users. The presence of copper IUDs does not interfere with sperm migration in vitro through human cervical mucus.
Prahalada S et al., 1985 Contraception
A single dose of MPA (Depo-Provera; Upjohn Co.; USA) was administered intramuscularly on day 27 (+/- 2) of gestation to three dosage groups of pregnant baboons. The dosage expressed as mg/kg corresponded to 1 (2.5 mg/kg), 10 (25 mg/kg) and 40 (100 mg/kg) times the human contraceptive dose equivalent (HDE) based on body weight. Injectable MPA was not teratogenic in baboons at 1x HDE. The teratogenicity was confined to the higher doses which included malformations of the external genitalia at 10x and 40x HDE and adrenal gland hypoplasia at 40x HDE. The maternal serum MPA concentrations were high during the critical period of adrenal and genital development. The pattern of MPA concentrations in maternal sera was similar between animals in the low dose group (10x HDE). In contrast, animals in the high dose group (40x HDE) showed interanimal variations in maternal serum concentrations of MPA. This study has demonstrated that injectable MPA is not teratogenic in baboons at human contraceptive dose equivalent and, even at higher doses, does not result in any nontarget organ malformations.
Lesko SM et al., 1985 Gastroenterology
The risk of Crohn's disease in relation to oral contraceptive use was evaluated in a hospital-based, case-control study of 57 women with Crohn's disease and 2189 controls with other conditions. The relative risk for oral contraceptive users compared with women who had never used these drugs was 1.9 (95% confidence interval 1.0-3.5). The magnitude of the relative risk estimate was related to the timing and duration of oral contraceptive use. For use within the year before admission to a hospital (recent use), the relative risk estimate was 4.3 (2.1-8.7); the estimate dropped to 1.2 (0.5-2.6) 4 yr after discontinuation of oral contraceptive use. The relative risk estimate for recent use that lasted greater than or equal to 5 yr was 8.0 (3.1-21). The findings are in accordance with earlier reports of an increased risk of Crohn's disease in oral contraceptive users.
Daly KJ et al., 1985 Can J Public Health
This study examined the characteristics and attitudes of 132 married couples who had received training in use of the symptothermal method of natural family planning (NFP). 61% of respondents were 20-30 years of age and over 2/3 had completed college; 59% were Catholic. The largest group of subjects (35%) became aware of NFP through friends, neighbors, and relatives. 71% said they were drawn to NFP because it represented a safe and healthy alternative to other methods of birth control; only 17% gave moral or religious reasons for learning about NFP. 42% of the sample were using NFP at the time of the survey, 32% had discontinued use, and 25% were using fertility awareness in conjunction with barrier methods (combination-continuers). There was a significant difference between these 3 groups in church attendance: 48% of combination-continuers and 67% of continuers compared with 41% of discontinuers attended church once a week or more. The combination-continuer group had more Catholics (50%) than the discontinuer group (37%) but less than the continuers (76%). No significant differences were found between the 3 groups in terms of age, education, or regularity of menstrual cycle length. Over 3/4 of continuers had been married for less than 5 years compared with about 1/2 of those in the 2 other groups. 69% of continuers believed that NFP is extremely effective compared to 13% of discontinuers and 40% of combination-continuers. Spouses encouraged each other in the use of NFP in 88% of combination-continuer couples and 86% of continuer couples, but only about half of discontinuers received such encouragement. Although most NFP advocates emphasize a nonsexual form of abstinence during the fertile period, the vast majority of respondents in this study defined abstinence to include the possibility of orgasm. Combination-continuers, positioned between continuers and discontinuers or both dissatisfaction with other methods and with abstinence, warrant more attention in future NFP research.
Sivin I et al., 1984 Contraception
First year results of a randomized study of 1509 users of the Copper T380Ag with a silver core or of an IUD releasing 20 mcg day of levonorgestrel are reported. The cumulative gross pregnancy rate for each device was 0.3 per 100 at one year, with more than 490 women having one year of use with each device. The levonorgestrel-releasing device was associated with significantly fewer bleeding days and significantly increased hemoglobin levels when compared with pre-admission values or the one year values observed among users of the TCu380Ag. Terminations attributable to amenorrhea were significantly more frequent among users of the levonorgestrel-releasing device. The TCu 380Ag was associated with increased frequency and severity of dysmenorrhea compared with pre-admission levels or with the steroid-releasing device. Hemoglobin levels were somewhat reduced among users of the TCu 380Ag device. Terminations attributable to pain were, however, not significantly different by device. Continuation rates at the end of the first year were not significantly different by device.
Conner GL et al., 1984 J Soc Serv Res
Factors associated with discontinuation from an island-wide natural family planning program in Mauritius were examined in 2 stratified random samples of 300 (1976) and 350 (1980) acceptors. The data were gathered through records, educator observations, and field interviews with the 1980 sample. Comparison between those served by the Action Familiale program and characteristics of the Mauritius population as a whole suggests that the natural family planning program serves a somewhat better educated group of couples who have more employment security and smaller families than the general population. Acceptors selected the natural family planning method for reasons such as a desire to have a child according to a plan or to space children (29%), avoidance of the side effects of artificial contraception (21%), or as a result of a recommendation by a friend, relative, or professional (25%). 74% of acceptors in the 1980 sample expressed satisfaction with the method and indicated that their spouse shared this satisfaction. After 3.5-4.5 years of follow-up, 57% of acceptors in the 1976 sample had discontinued use of natural family planning. 9 variables in 4 categories--Administrative, Psychological-Motivational, Educator-Acceptor Relationship, and Family--were predictive of discontinuation. The major factors differentiating discontinuers from continuers were: 1) discontinuers had previously registered at Action Familiale and dropped out; 2) discontinuers placed more emphasis on spacing than on preventing pregnancies; 3) discontinuers discussed fewer topics with their educators; 4) discontinuers and their husbands seemed less interested in the natural method; 5) discontinuers had less family support for natural family planning; 6) educators experienced greater difficulty in teaching discontinuers; 7) discontinuers demonstrated less understanding of the symptothermal method; and 8) educators made fewer preregistration visits to the homes of discontinuers.
Verzosa CC et al., 1984 Stud Fam Plann
Two sets of focus group discussions on the advantages and disadvantages of the rhythm method were carried out in the Philippines in 1980 and 1981. The first discussions were held among 30 women and nine men 21-40 years of age, and the second among eight women 25-35 years of age who had voluntary pregnancy terminations after the method had failed. Among the perceived advantages of rhythm were that it permits spontaneous intercourse on the safe days and has no bad side effects. Among the perceived disadvantages were that it is ineffective, especially for women with irregular periods, and it requires abstinence. The women who had had voluntary pregnancy terminations discussed their motivations and rationales and the methods that they had used. The information obtained from the discussions formed the basis for support materials that are now used throughout the country.
Bagdade JD et al., 1982 Arteriosclerosis
Pooled serum from women taking a combined estrogen-progestin oral contraceptive preparation caused significantly greater cell proliferation and incorporation of 3H-thymidine into DNA in both human arterial smooth muscle cells and dermal fibroblasts in tissue culture than did serum from controls. A portion of this mitogenic effect appears to be related to the presence of a factor(s) that is heat stable, nondialyzable, and contained in the lipoprotein-deficient serum fraction. In vitro addition of varying concentrations of mestranol and norethindrone, the two constituents of the oral contraceptive preparation taken by participants in the study, to control serum did not enhance its mitogenicity, suggesting that the effect observed with intact serum was due either to a metabolite of these compounds or to the production of other growth-promoting substances during oral contraceptive treatment. Since smooth muscle cell proliferation is an integral feature of all atherosclerotic lesions, these findings provide some insights applicable to understanding the pathogenesis of vascular disease associated with oral contraceptive use.
Linn S et al., 1982 JAMA
Interview data from 3,214 married women having planned pregnancies and singleton deliveries who had no history of fertility treatment and who conceived more than two weeks after cessation of contraception were analyzed. The interval from cessation of contraception to conception was 13 months or greater for 24.8% of prior "pill" users vs 10.6% for former users of all other methods. As compared with former users of other methods, pill users had a notably lower monthly percentage of conceptions for the first three months and somewhat lower percentage from four to ten months. Results were not altered when potential confounding variables were controlled by logistic regression. At least 15 months of unsuccessful trials might be a more appropriate working definition of infertility for previous pill users rather than the 12-month interval generally accepted for this purpose.
Bolton GC, 1981 Clin Obstet Gynecol
Both the medical profession and the general public are becoming more and more aware of the need for adolescent contraception and the devastating consequences of the lack of such care. It is the responsibility of family planning providers and educators to offer this type of service tailored to adolescents and their unique needs. The service must include counseling, education, provision of contraceptives, and followup medical care. To better understand adolescent contraception, it is necessary to understand adolescent sexuality, the teenage pregnancy problem, the risks of teenage pregnancy, and the unique aspects of the contraceptive methods available to teenagers. Each of these areas is reviewed. The most important developmental task of adolescence relates to sexual maturation. The child's body undergoes complex changes necessary for adult function, and the sex drive is awakened. The teenager is faced with the task of developing a sexual identity and personal values about sexual behavior. The 2 important tasks in sexual counseling of the adolescent are helping them to decide whether or not they are ready for sexual intimacy and encouraging them to assume responsibility for their sexual behavior. The consequences of adolescent sexual activity are the rise in teenage sexually transmitted diseases and the rise in teenage pregnancies. Medically, the hazards of an adolescent pregnancy include: an overall increase in incidence of infant mortality 2-3 times that of the normal population; twice as many growth retarded infants born to teen mothers; maternal mortality 60% higher than normal; a low incidence of prenatal care early in pregnancy; and 27% of pregnancies terminated by abortion. Equally important are nonmedical consequences for the teenage parent. In general, the consequences of teen parenthood are more severe for the young mother than for the young father. Teen mothers have a suicide rate 10 times that of the general population. In discussing contraception, attention is directed to all available contraceptive methods (abstinence, sex without intercourse, natural family planning, withdrawal, condoms and vaginal spermicidal agents, diaphragm, IUDs, and abortion), but emphasis is on oral contraceptives (OCs). The popularity of OCs among adolescents is due primarily to 2 factors: the agents are highly effective and their use is not associated directly with the act of coitus. For the physician, there are 2 concerns associated with the use of these exogenous steroids in the not fully mature patient: administration might cause premature closure of the epiphyses and inhibition of full stature development; and the steroids might cause permanent hypothalamic-pituitary dysfunction. Both concerns are relatively unwarranted. The OC might be an excellent choice for the adolescent without medical contraindication, who has established regular menses, and who has intercourse on a regular or fairly frequent basis.
Serra A, 1981 Bull Nat Fam Plan Counc Vic
Genetic errors of many kinds are connected with the reproductive processes and are favored by a nunber of largely uncontrollable, endogenous, and/or exogenous factors. For a long time human beings have taken into their own hands the control of this process. The regulation of fertility is clearly a forceful request to any family, to any community, were it only to lower the level of the consequences of genetic errors. In connection with this request, and in the context of the Congress for the Family of Africa and Europe (Catholic University, January 1981), 1 question must still be raised and possibly answered. The question is: do or can the so called "natural methods" for the regulation of fertility increase the risks of genetic errors with their generally dramatic effects on families and on communities. It is important to try to give as far as possible a scientifically based answer to this question. Fr. Haring, a moral theologian, citing scientific evidence finds it shocking that the rhythm method, so strongly and recently endorsed again by Church authorities, should be classified among the means of "birth control" by way of spontaneous abortion or at least by spontaneous loss of a large number of zygotes which, due to the concrete application of the rhythm method, lack of necessary vitality for survival. He goes on to state that the scientific research provides overwhelming evidence that the rhythm method in its traditional form is responsible for a disproportionate waste of zygotes and a disproportionate frequency of spontaneous abortions and a defective childern. Professor Hilgers, a reproductive physiologist, takes on opposite view, maintaining that the hypotheses are arbitrary and the alarm false. The strongest evidence upon which Fr. Haring bases his moral principles about the use of the natural methods of fertility regulation is a paper by Guerrero and Rojos (1975). These authors examined, retrospectively, the success of 965 pregnancies which occurred in women who were using the temperature method for family planning and who had recorded the menstrual day of insemination, and they concluded that their results suggested that aging of human spermatozoa in the female genital tract is associated with a increased frequency of spontaneous abortions and that postovulatory aging of human ova results in postimplatation. Their results and conclusions were accepted with great caution by the scientific community. The kind of evidence which suggests that the use of natural methods may increase, in particular cases, the loss of embryos or fetuses, stimulates further research, but it seems a very weak basis for the establishment of principles of human behavior. At the present stage of knowledge the natural methods for the regulation of fertility cannot be qualified as methods which necessarily and considerably increase the risks of abortion of malformed progeny.
Currie JN et al., 1980 Med J Aust
3 cases of stroke in young women of childbearing age are presented to show the severity of illness and mortality in women using oral contraceptives. All 3 patients smoked more than 15 cigarettes a day. The mortality rate from cerebrovascular disease in OC users has been estimated as 4.7 times that of nonusers. The risk of developing a thrombotic stroke is 9.5 times greater than a control group's. Cerebral infarction has a relatively low mortality rate in young women, 9%, but a nonfatal stroke can have a devastating effect on the patient and her family. While there were no deaths among the 3 cases, each was left with a varying degree of neurological deficit while still in the peak of a normal life span. The possibility of synergistic potentiation of OC-associated cerebral thrombosis by cigarette use is uncertain but studies have noted some correlation between the 2. It is not clear that reduction in estrogen dosage has reduced the risk of cardiac or cerebral disease. The first patient developed extreme symptoms after a heavy drinking session, thereby raising the question of alcohol as a precipitating factor.
Vessey M et al., 1976 J Biosoc Sci
Summary In 1968, a prospective study was started in collaboration with the Family Planning Association to try to provide a balanced view of the beneficial and harmful effects of different methods of contraception. This investigation is now in progress at seventeen clinics and over 17,000 women are under observation. At the time of recruitment, all these women were married white British subjects, aged 25–39 years, who voluntarily agreed to participate. Fifty-six per cent were using oral contraceptives, 25% were using a diaphragm and 19% were using an intrauterine device (IUD). During follow-up each woman is questioned at return visits to the clinic and a record of pregnancies and their outcome, hospital referrals (inpatient or outpatient), changes in contraceptive methods and the results of cervical smears, is accumulated. Women who default are sent a postal questionnaire and, if this is not returned, are telephoned or visited in their homes to collect the necessary information. So far, data obtained during 56,000 woman-years of observation are available for analysis. Follow-up has been maintained with an annual lapse rate of about 0.3%due to withdrawal of co-operation or loss of contact; adherence to the method of contraception in use at recruitment has been reasonably good, and the reporting of pregnancies and hospital admissions appears to have been both reliable and unbiased. The present data include only 24 deaths, so the mortality associated with different contraceptive methods cannot yet be estimated. With regard to morbidity, however, our preliminary results closely resemble those obtained in the prospective study carried out by the Royal College of General Practitioners (1974) and in the principal retrospective studies carried out in Britain and the United States. Women who used oral contraceptives at the start of the study experienced a deficiency of hospital referrals for cancer, benign lesions of the breast, menstrual disorders other than amenorrhoea, duodenal ulcer, and retention cysts of the ovary; they showed an excess of referrals for cerebrovascular disease, cervical erosion, skin disorders, self-poisoning, migraine, venous thrombosis and embolism, hayfever, gallbladder disease, amenorrhoea, and sterility. Women who used a diaphragm showed a deficiency of hospital referrals for carcinoma-in-situ and dysplastic lesions of the cervix uteri and accidental injury; and an excess of referrals for haemorrhoids and cystitis. Women who used an IUD experienced an excess of hospital referrals for anaemia, varicose veins and salpingitis. About half of these differences (12 out of 23) were predicted from other studies while some suggestive evidence already existed for a further five. Of the remaining six, some probably reflect the influence of selective factors or chance. Multiple pregnancies, stillbirths, malformations, the sex ratio and birthweight showed no consistent relationship to method of contraception. The outcome of unplanned pregnancies occurring in women using an IUD, however, was remarkably unfavourable both in terms of ectopic gestation and miscarriage. Clear evidence was found of impairment of fertility after discontinuation of oral contraceptives. Whether this is likely to lead to permanent sterility in some women is uncertain. The study has provided data on the efficacy of a wide variety of contraceptive methods. In general the failure rates are in keeping with those obtained in other large-scale studies, save that those for the diaphragm and the sheath are much lower than those usually quoted. The available evidence does not yet allow a final balance to be struck between the benefits and risks associated with the new methods of contraception that have become widely used during the last two decades. It seems clear, however, that there are no material risks associated with the use of the diaphragm apart from the risk of pregnancy and that there may be some unintended benefits.
Mernissi F, 1975 Stud Fam Plann
Sixty in-depth interviews with mothers living in a urban slum of Morocco probed resistances to practicing modern methods of fertility control and began to shed light on some of the reasons family planning programs often fail to reach illiterate target populations. Economic insecurity and the disintegration of the support networks of the traditional extended family complicate the difficult lives of young mothers in the urban slum. While such factors tend to encourage smaller families, the uncertainties and complexities of the socioeconomic structure contribute to the problems blocking access to modern methods of fertility control.
Lewitt S et al., 1971 Fertil Steril
The use-effectiveness of oral contraception and intrauterine contraception was studied in 3 family planning centers in the United States: Grady Memorial Hospital in Atlanta, Georgia; State University of New York, Downstate Medical Center, in Brooklyn; and the Planned Parenthood Center in Buffalo, New York. In each locality 1000 women were selected for the study. 2900 women accepted intrauterine devices (IUDs) or oral contraceptives (OCs) as their first method of contraception. In Brooklyn 3 out of 4 women chose OCs; in Atlanta and Buffalo roughly equal numbers selected each method. The mean age of admission was 25.7 years in Buffalo, 24 years in Brooklyn, and 23.8 years in Atlanta. IUD acceptors were older than those choosing OCs. The difference was greatest in Buffalo (3.3 years) and smallest in Atlanta (.8 years). A special one-page, self-coding questionnaire was designed to collect the information required. In all 3 clinics contraceptive termination rates were markedly lower for the IUDs than for OCs. At 1 year of use for the first method only about one-fourth the women who chose the IUD had discontinued its use. Women on OCs terminated at rates from 10-20% higher. Termination rates for all contraception, both first-method and substitution, were lower than for first-method alone and lower for IUDs than for OCs. The highest continuation rate for all contraception was 92.5% for IUD users in Brooklyn while OC users in Atlanta were at the lowest level at 60.5%. Pregnancy rate studies demonstrated higher failure rates with OCs than with IUDs in all 3 clinics. Statistics by age showed that termination rates for both IUD and OC users declined with age. Women who selected IUDs as their method of contraception were more persistent users of contraception. Even after discontinuing IUD use, they were more likely to adopt another contraceptive method.
Lewit S et al., 1971 Fam Plann Perspect
The extended use-effectiveness of IUD and oral pills as measured by 1) their theoretical effectiveness 2) consistency of use and 3) continuation of use in preventing unwanted pregnancies was studied for 2900 women who had chosen either method as their first contraceptive in family planning clinics in Atlanta Georgia and in Brooklyn and Buffalo New York for a 12-18 month period. The greater persistence among IUD users to continue the method or use another method and the less likelihood there was of these women to have an unplanned pregnancy (the difference between IUD users and pill users increasing with months of exposure) suggest the necessity of greater support from the clinics to help women using pills prevent unwanted pregnancies. IUD users were generally older than pill acceptors and among IUD contraceptors the greater tendency to continue using the IUD and contraception may indicate that older women use contraception to terminate rather than to space childbirth.
Odeblad E, 1968 Acta obstetricia et gynecologica Scandinavica
Tietze C, 1959 Am J Obstet Gynecol
Physiologic effectiveness is the measure of protection against unwanted pregnancy afforded by a specific contraceptive method under ideal conditions ie, used consistently and according to instructions-without omissions, or errors of technique. Such ideal conditions are rarely present. Even when they are, it is not practicable to observe and verify them. Physiologic effectiveness, although not accessible to direct measurement, is by definition higher than the observed clinical effectiveness of the same method in the hands of the most …
Brandao BM et al., 2025 Hormones and Behavior Open Access
Hormonal contraceptives (HCs) are widely used, yet their effects on emotional and cognitive processes remain poorly understood. This study examined how HC use may influence emotional reactivity, emotion regulation, and emotional memory. Female participants (N = 179), either using HCs (N = 87) or naturally cycling (NC; N = 92), were randomly assigned to one of three groups: no emotion regulation (control), distancing and immersion, or reinterpretation and immersion. The emotion regulation groups completed emotion regulation training in which they viewed emotional images while applying different emotion regulation strategies, followed by a surprise memory test. Overall, HC users showed greater emotional reactivity to emotional images compared to NC participants. Both HC and NC groups successfully applied emotion regulation strategies as measured by changes in emotional affect; however, distancing led to a greater reduction in negative emotions compared to reinterpretation, particularly among HC users. Both HC and NC groups showed better memory for positive images after applying immersion. For negative images, HC users showed reduced memory performance when applying either distancing or reinterpretation, an effect not observed in NC participants. These findings suggest that HC use may influence specific aspects of emotional processing and memory, highlighting the need for more nuanced research on the cognitive and emotional effects of hormonal contraceptives.
Zim A et al., 2025 Cureus
Combined oral contraceptives (COCs) possess the ability to alter the normal composition of the gut microbiome and the permeability of the gastrointestinal (GI) tract, which may cause both gut-related and non-gut-related complications. The gut-estrogen axis examines the relationship between estrogens (particularly the active form, estradiol) and the gastrointestinal system and can be attributed to the maintenance of the estrobolome and circulating estradiol levels. The gut-brain axis involves the relationship between the brain and the gastrointestinal system and can be attributed to the gut microbiome in relation to the enteric nervous system (ENS) and serotonin levels. Overall, the introduction of exogenous hormones into an endogenous environment alters the normal balance of both hormones and bacteria. Currently, there is a gap in knowledge regarding the link between COCs and mental health complications such as anxiety and depression, and the diversity in these complications may be related to different types of COCs, their composition, and variations in study populations. This article reviews existing evidence from animal and human studies on the role of COCs in the development of mental health issues through their impact on the gut microbiome.
Brito J et al., 2025 Journal of applied physiology (Bethesda, Md. : 1985) Open Access
Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m2 vs. 22 ± 4 yr, 23 ± 4 kg/m2; Ps ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps ≤ 0.01), with greater changes in Control (Ps ≤ 0.046) than HBC (Ps ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (Ps ≥ 0.473), β-diversity differed between Control and HBC groups (P = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.NEW & NOTEWORTHY This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.
Michaelsen MP et al., 2025 BJOG: An International Journal of Obstetrics and Gynaecology
To study the association between previous use of levonorgestrel intrauterine system (LNG-IUS) and endometrial thickness (EMT) in women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Multicentre historical cohort study. Eight Danish public and private fertility clinics. 12786 women aged 18-46 years contributing with an EMT measurement from 22 464 different IVF/ICSI treatment cycles between 2000 and 2021. Exposure was previous use of LNG-IUS, combined oral contraceptive pills (OCPs), progestogen-only pills (POPs), no/other contraception or combined, cumulated use of contraception when more contraceptives had been used during the inclusion period. LNG-IUS use was categorised into 0-3 years, >3-6 years, >6-9 years and >9 years. Mixed effect logistic regression adjusted for age, BMI, smoking, educational level, total FSH dose and fertility clinic was used. EMT (< 7 mm vs >= 7 mm). Statistically significantly higher odds of EMT >= 7 mm were found for OCPs [OR 3.53 (95% CI 1.29-9.65)], POPs [OR 6.43 (95% CI 1.45-28.63)] and no/other contraception [OR 6.67 (95% CI 2.37-18.74)] relative to LNG-IUS in IVF/ICSI cycles. All duration categories of ever use of LNG-IUS were associated with significantly lower odds of EMT >= 7 mm compared to no/other contraception. Previous use of LNG-IUS was associated with decreased endometrial growth in women undergoing IVF/ICSI.
Segarra I et al., 2023 Front Med (Lausanne) Open Access
Hormone-based contraception disrupts hormonal balance, creating artificial states of anovulation and threatening women's health. We reviewed its main adverse effects and mechanisms on accelerated ovarian aging, mental health (emotional disruptions, depression, and suicide), sexuality (reduced libido), cardiovascular (brain stroke, myocardial infarction, hypertension, and thrombosis), and oncological (breast, cervical, and endometrial cancers). Other "collateral damage" includes negative effects on communication, scientific mistrust, poor physician-patient relationships, increased patient burden, economic drain on the healthcare system, and environmental pollution. Hormone-sensitive tumors present a dilemma owing to their potential dual effects: preventing some cancers vs. higher risk for others remains controversial, with denial or dismissal as non-relevant adverse effects, information avoidance, and modification of scientific criteria. This lack of clinical assessment poses challenges to women's health and their right to autonomy. Overcoming these challenges requires an anthropological integration of sexuality, as the focus on genital bodily union alone fails to encompass the intimate relational expression of individuals, complete sexual satisfaction, and the intertwined feelings of trust, safety, tenderness, and endorsement of women's femininity.
Duane M et al., 2023 PEC Innov Open Access
To assess patient experiences using a Shared Decision-Making (SDM) Tool for fertility awareness-based methods (FABMs) of family planning. The study employed a prospective crossover design to evaluate impact of the SDM tool compared to usual practice when discussing FABMs with patients. Patients completed preand post-office visit surveys and an online survey six months later. The primary outcomes evaluated the effect of the SDM tool on patient satisfaction and FABM continuity of use rates. There was no significant difference in likelihood of changing family planning methods immediately after the office visit; however, by six months a significantly larger proportion of patients had started or changed FABMs in the experimental group (52%, 34/66) compared to the control group (36%, 24/66) (p = 0.04). Significantly more patients who used the tool and changed their FABM after their visit reported increased satisfaction with their FABM compared to control (50% vs. 17%, p = 0.022). Use of the SDM tool increased persistent use of and satisfaction with chosen FABMs at six months. The novel SDM tool can enhance patients' understanding and facilitate the selection of a more suitable method leading to increased satisfaction.
White L et al., 2023 Br J Sports Med
Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. Data Sources: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. This review was registered on PROSPERO CRD42021224582 on 8 January 2021.
Duane M et al., 2023 PEC Innov Open Access
To assess the impact of a Shared Decision-Making (SDM) tool for fertility awareness-based methods (FABMs) of family planning. Clinicians familiar with at least one FABM were randomly invited to participate in a prospective cross-over study to compare usual practice to the use of the SDM tool when discussing FABMs with patients. Patients completed surveys preand post-office visit and six months later. The primary outcome explored the effect of online education on use of the SDM tool on clinicians' knowledge of FABMs. Of 278 clinicians contacted, 54% could not be reached, and 15% did not provide women's health services. The 26 clinicians enrolled were experienced, with more than half recommending FABMs for ≥10 years, and 73% recommending more than one FABM to patients. Knowledge scores significantly improved after online training and use of the SDM tool (baseline mean score = 9.54 (scale of 0-12); post-training mean score = 10.73, p < 0.002). Education about FABMs and training on use of the SDM tool improved knowledge scores even among an experienced cohort of clinicians. The novel SDM tool can better equip clinicians to meet the rising patient interest in FABMs.
Mosorin ME et al., 2023 J Clin Med Open Access
This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.
Larsen SV et al., 2023 JAMA Psychiatry Open Access
Hormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span. To determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation. DESIGN, SETTING, This cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery. Exposures: Prior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication. Crude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery. Of 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non-HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]). Conclusions and Relevance: These findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.
Fitzpatrick D et al., 2023 PLoS medicine
Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.
Yousuf SD et al., 2023 BMC Women's Health
Background Polycystic ovary syndrome (PCOS) presents clinical symptoms of menstrual abnormalities, excessive hair growth (hirsutism), scalp hair loss, acne and infertility. Metabolic abnormalities such as obesity, insulin resist‑ ance, glucose intolerance and cardiovascular problems constitute an essential part of PCOS, all of which can have significant long-term health consequences. Low-grade chronic inflammation demonstrated by persistent moderately elevated serum levels of inflammatory and coagulatory markers plays a critical role in the pathogenesis of PCOS. Oral contraceptive pills (OCPs) constitute the mainstay of pharmacologic therapy for women with PCOS to regularize cyclicity and ameliorate androgen excess. On the other hand, OCP use is associated with various venous thromboem‑ bolic and proinflammatory events in the general population. PCOS women always carriers the increased lifetime risk of these events. The studies on the effect of OCPs on inflammatory, coagulation and metabolic parameters in PCOS are less robust. Therefore in this study, we investigated and compared the messenger RNA (mRNA) expression profiles of genes implicated in inflammatory and coagulation pathways between drug-naive and OCP-treated PCOS women. The selected genes include intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), mono‑ cyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, the correlation between the selected markers and various metabolic indices in the OCP group has also been explored. Method The relative amounts of ICAM-1, TNF-α, MCP-1 and PAI-1 mRNA in peripheral blood mononuclear cells from 25 drug-naive PCOS subjects (controls) and 25 PCOS subjects who received OCPs containing 0.03 mg-ethinyl-estra‑ diol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical Open Access Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, involving 6–20% percent of women of reproductive age [ 1 ], with an even greater incidence among Kashmiri women [ 2 ]. Apart from the symptoms of hyperandrogenism and infertility, PCOS is associated with several metabolic abnormalities, including obesity, insulin resistance (IR), hyperlipidemia, systemic inflammation and functional atherosclerosis [ 3 – 5 ]. Elevated inflammatory and coagulatory markers characterize this low-grade inflammation and endothelial dysfunction. Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) are potent biological markers for the development of inflammatory and metabolic diseases which may include PCOS [ 6 – 8 ]. ICAM-1 belongs to the super immunoglobulin family and is produced mainly on cell surfaces of endothelial cells, smooth muscle cells, macrophages and activated lymphocytes. It is required for the adhesion of freely moving leukocytes to blood vessel walls and trans-endothelial migration to the vascular intima. This action is crucial in the evolution of atheroma from early to advanced stages. Cleavage of membranebound ICAM-1 results in circulating soluble ICAM-1 (sICAM-1) [ 9 , 10 ]. In prospective epidemiologic investigations, its levels in serum have been linked to abdominal obesity, insulin resistance and cardiovascular disease (CVD) [ 11 ]. TNF-α, a cytokine released by adipose tissue, instigates insulin resistance. In the endothelium, the TNF-α signaling pathway, which is regulated by nuclear factor kappa B (NF-KB), governs the expression of adhesion molecules such as sICAM-1 [ 12 ]. Many studies have found that women with PCOS have significantly higher ICAM-1, MCP-1 and TNF-α than women without PCOS [ 13 , 14 ]. interpretation was conducted using SPSS version 20.0 (SPSS, Inc, Chicago, IL), Epi Info version 2002 (Disease Control and Prevention Centres, Atlanta, GA) and GraphPad Prism 5 (GraphPad Software, La Jolla, CA) software. Result Six months of OCP therapy enhanced the expression of inflammatory genes viz ICAM-1, TNF-α and MCP-1 mRNA in PCOS women by 2.54, 2.05 and 1.74 folds, respectively, in this study. However, PAI-1 mRNA in the OCP group showed no significant increase. Furthermore, in cases, ICAM-1 mRNA expression positively correlated with body mass index (BMI) (p = 0.01), fasting insulin (p = 0.01), insulin 2 h p = 0.02), glucose 2 h (p = 0.01) and triglycerides (p = 0.01). TNF-α mRNA expression positively correlated with fasting insulin (p = 0.0007). MCP-1 mRNA expression positively cor‑ related with (BMI) (p = 0.002). Conclusion OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. [truncated]
Brouillard A et al., 2023 Frontiers in endocrinology
Endogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake. We investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network. We recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users' salivary ethinyl estradiol (EE) were assessed using liquid chromatography - tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods. Compared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs. Our results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.
van Bommel MHD et al., 2022 Hum Reprod Update
Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods. Outcomes: Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36-1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90-1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52-0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38-0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26-0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53-1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients' preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.
Alonso-Molero J et al., 2022 Menopause
To extend knowledge about the long-term use of hormones in hormone therapy or oral contraception as prognostic factors in breast cancer. The MCC-Spain project is a cohort of 1,685 women with incident breast cancer recruited in Spain. Recruitment was carried out between 2007 and 2010, and the follow-up finished in December 2017. The impact of hormone therapy or oral contraception on breast cancer prognosis was analyzed considering year of birth and menopausal status (1,095 women [65%] were postmenopausal). Hazard ratios (HRs) were estimated using Cox regression models. Death by any cause was considered as the event, and hormone therapy or oral contraception were analyzed as regressors. Oral contraception use for less than 5 years shows an HR of 1.10 (95% CI, 0.75 to 1.62), whereas use for 5 or more years shows an HR of 1.46 (95% CI, 0.95 to 2.25), with a P trend of 0.01, showing a dose-dependent response. Regarding hormone therapy and restricting the analysis to postmenopausal women born between1940 and 1959, where most hormone therapy (consumption) is concentrated, the results did not show any trend. Concerning oral contraception use, our results demonstrate that their use is related to poor prognosis in breast cancer. However, research in this field is limited and controversial, indicating the need for more research in this area. Regarding hormone therapy consumption, our results indicate no association with better prognosis, which contradicts what has previously been published.
Casto KV et al., 2022 Frontiers in neuroendocrinology
Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.
Niemeyer Hultstrand J et al., 2022 Lancet Reg Health Eur Open Access
Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods. In this nationwide prospective cohort study, all Swedish women aged 15-34 at study start on January 1(st) 2005, or who turned 15 years during the study period, were followed until December 31(st) 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer. Findings: This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91-1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20-1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14-1.69); progestogen-only methods IRR 1.74 (1.44-2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods. Interpretation: Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling. This study was funded by the Swedish Cancer Society and by the Uppsala County Council, the Faculty of Medicine at Uppsala University.
Manhart MD et al., 2022 Contraception
The Natural Cycles app employs daily basal body temperature to define the fertile window via a proprietary algorithm and is clinically established effective in preventing pregnancy. We sought to (1) compare the app-defined fertile window of Natural Cycles to that of CycleProGo, an app that uses BBT and cervical mucus to define the fertile window and (2) compare the app-defined fertile windows to the estimated physiologic fertile window. Daily BBT were entered into Natural Cycles from 20 randomly selected regularly cycling women with at least 12 complete cycles from the CycleProGo database. The proportion of cycles with equivalent (±1 cycle day) fertile-window starts and fertile-window ends was determined. The app-defined fertile windows were then compared to the estimated physiologic fertile window using Peak mucus to estimate ovulation. Fifty seven percent of cycles (136/238) had equivalent fertile-window starts and 36% (72/181) had equivalent fertile-window end days. The mean overall fertile-window length from Natural Cycles was 12.8 days compared to 15.1 days for CycleProGo (p < 0.001). The Natural Cycles algorithm declared 12% to 30% of cycles with a fertile-window start and 13% to 38% of cycles with a fertile-window end within the estimated physiologic fertile window. The CycleProGo algorithm declared 4% to 14% of cycles with a fertile-window start and no cycles with a fertile-window end within the estimated physiologic fertile window. Natural Cycles designated a higher proportion of cycles days as infertile within the estimated physiologic fertile window than CycleProGo. Use of cervical mucus in addition to BBT may improve the accuracy of identifying the fertile window. Additional studies with other markers of ovulation and the fertile window would give additional insight into the clinical implications of app-defined fertile window differences.
Zareian B et al., 2022 BMC Womens Health Open Access
The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females' risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning. Using a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels. In this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.
Anastasiou E et al., 2022 Contraception Open Access
tudies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection. Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725). Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association. We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk. Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
Peebles K et al., 2021 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Open Access
Limited evidence suggests that the nonhormonal contraceptive copper intrauterine device (Cu-IUD) may increase bacterial vaginosis (BV) risk, possibly due to increased volume and duration of menses, a common side effect of Cu-IUD use. Although increases in bleeding typically resolve within 6-12 months following initiation, evaluations of the association between Cu-IUD and BV have not included more than 6 months of follow-up. This secondary analysis of a human immunodeficiency virus type 1 prevention trial included 2585 African women ages 18-45 followed for up to 33 months. Women reported contraceptive use each month. BV was evaluated by Nugent score in 6-monthly intervals and, if clinically indicated, by Amsel criteria. Andersen-Gill proportional hazards models were used to (1) evaluate BV risk among Cu-IUD users relative to women using no/another nonhormonal contraceptive and (2) test changes in BV frequency before, while using, and following Cu-IUD discontinuation. BV frequency was highest among Cu-IUD users at 153.6 episodes per 100 person-years (95% confidence interval [CI]: 145.2, 162.4). In adjusted models, Cu-IUD users experienced 1.28-fold (95% CI: 1.12, 1.46) higher BV risk relative to women using no/another nonhormonal contraception. Compared to the 6 months prior to initiation, BV risk was 1.52-fold (95% CI: 1.16, 2.00) higher in the first 6 months of Cu-IUD use and remained elevated over 18 months of use (P < .05). Among women who discontinued Cu-IUD, BV frequency was similar to pre-initiation rates within 1 year. Cu-IUD users experienced elevated BV risk that persisted throughout use. Women and their providers may wish to consider BV risk when discussing contraceptive options.
Shamseddin M et al., 2021 EMBO molecular medicine
Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist- and levonorgestrel-induced RANKL expression and reduces levonorgestrel-driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.
Iversen L et al., 2021 Int J Cancer Open Access
To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person-years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval [CI] 1.10-1.29). Increased risks were seen in current or recent users of any hormonal: RR 1.30 (95% CI 1.20-1.42) and combined: RR 1.40 (95% CI 1.28-1.53), but not progestin-only contraception: RR 0.91 (95% CI 0.78-1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05-1.60) and squamous cancer (RR 1.31, 95% CI 1.19-1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.
Frank S et al., 2021 Perm J Open Access
Catamenial epilepsy (CE) is exacerbated by hormonal fluctuations during the menstrual cycle. Approximately 1.7 million women have epilepsy in the United States. CE affects more than 40% of women with epilepsy. There is a paucity of literature addressing this condition from a clinical standpoint, and the literature that does exist is limited to the neurological community. This article reviews the diagnosis and management of CE for the non-neurologist. Women with CE have early touch points in their care with numerous health care providers before ever consulting with a specialist, including OB/GYNs, pediatricians, emergency department physicians, and family medicine providers. In addition, women affected by CE have seizures that are more recalcitrant to traditional epilepsy treatment regimens. To optimize management in patients affected by CE, menstrual physiology must be understood, individualized hormonal contraception treatment considered, and adjustments and interactions with antiepileptic drugs addressed. Observations: CE is a unique subset of seizure disorders affected by menstrual fluctuations of progesterone and estrogen. The diagnosis of CE has been refined and clarified. There is an ever-increasing understanding of the importance and variety of options of hormonal contraception available to help manage CE. Furthermore, antiepileptic drugs and contraception can interact, so attention must be directed to optimizing both regimens to prevent uncontrolled seizures and pregnancy. CE can be diagnosed with charting of menstrual cycles and seizure activity. Hormonal treatments that induce amenorrhea have been shown to reduce CE. Optimizing antiepileptic drug dosing and contraceptive methods also can minimize unplanned pregnancies in women affected by CE.
Sims ST et al., 2021 BMJ open sport & exercise medicine
As the number of female athletes competing rises globally, training methodologies should reflect sex differences across critical metrics of adaptation to training. Surrogate markers of the autonomic nervous system (ANS) used for monitoring training load are heart rate variability (HRV) and resting heart rate (RHR). The aim was to investigate ovarian hormone effects on standard recovery metrics (HRV, RHR, respiratory rate (RR) and sleep duration) across a large population of female athletes. A retrospective study analysed 362 852 days of data representing 13 535 menstrual cycles (MC) from 4594 respondents (natural MC n=3870, BC n=455, progestin-only n=269) for relationships and/or differences between endogenous and exogenous ovarian hormones on ANS. HRV and return to baseline (recovery) decreased as resting HR and RR increased (p<0.001) from the early follicular to the late luteal phase of the MC. Patterning was paradoxical across phases for users of combined hormonal contraception (BC) as compared with the patterning of the MC. HRV and recovery start elevated and drop off quickly during the withdrawal bleed, rising through the active pill weeks (p<0.001). Progestin-only users had similar patterning as the MC. The relationship between normalised recovery and previous day strain is modulated by birth control type. BC exhibited steeper declines in recovery with additional strain-normalised recovery decreases by an additional 0.0055±0.00135 (p<0.001) per unit of strain; with no significant difference between MC and progestin-only (p=0.19). The patterning of ANS modulation from ovarian hormones is significantly different between naturally cycling women and those on BC, with the patterning dependent on the type of contraception used.
Larsen SV et al., 2020 Acta Psychiatr Scand Open Access
Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. [(11)C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], P(corrected) = 0.03). We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.
Kaneshiro B et al., 2020 Hawaii J Health Soc Welf
Long acting reversible contraceptives (LARC), including intrauterine devices (IUDs) and contraceptive implants, can support an individual in meeting their reproductive goals by allowing them to prevent pregnancy effectively. These devices can also limit an individual's control over reproduction because they generally require an in-person visit to a health care provider for removal. Returning for another visit may be logistically challenging for many individuals who may need to arrange for transportation, childcare, or take time off from work. Effectively negotiating with a provider to request removal may be additionally challenging for medically underserved and disenfranchised people who may not feel empowered to do so. The objective of this study was to assess providers' willingness to honor patients' requests for IUD and contraceptive implant removal on the day of the request. A survey was conducted in which clinicians were presented with scenarios of women requesting IUD or implant removal. Clinicians were asked what they were most likely to do. A total of 105 clinicians were surveyed. The responses of 60 clinicians who inserted IUDs and 57 who provided the contraceptive implant were included in the analysis. When asked about same-day removal of an IUD or implant from a dissatisfied patient who requested removal, 40% stated they would remove the implant, and 57% stated they would remove the IUD on the day of the request. Findings from this study suggest many clinicians would be unwilling or unable to accommodate a patient's request for device removal at the time of their visit. This delay or refusal represents a significant barrier for patients and has implications for reproductive autonomy that should be further explored.
Thompson A et al., 2020 Cureus Open Access
It has been well documented that female sex is a significant risk factor for the development of various autoimmune diseases. While the reason for this has been debated, one well-regarded theory is that increased estrogen and decreased testosterone play a role in this predisposition. Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is an autoimmune disorder that affects over nine million women in the United States. It presents with pelvic and bladder pain and urinary symptoms, both of which significantly and negatively affect the quality of life. Even so, very few studies have examined the pathophysiologic relationship between autoimmune disorders and hormonal contraceptives. In this report, we present a case of IC likely precipitated by oral contraceptives (OCPs) in a premenopausal female. Shortly after beginning OCPs, this patient developed symptoms of severe pelvic pain and increased urinary frequency. Over the course of a year, the patient was diagnosed and treated for a variety of conditions, such as urinary tract infection (UTI), fungal vaginitis, and nephrolithiasis. After consultation with a gynecologist, a normal abdominal CT scan, and unsuccessful cystoscopy due to pain, she was finally diagnosed with IC. The patient independently learned of a potential link between hormonal contraceptive pills and IC and decided to discontinue this method of birth control. Following this, her symptoms completely resolved within several months. The timing of her initiation and discontinuation of OCPs, alongside her symptomatology, suggest a connection to the development of IC. A literature review was performed, which supports this association. We, therefore, highlight this case as an important example of IC precipitated by OCPs.
Asthana S et al., 2020 Eur J Obstet Gynecol Reprod Biol
Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear. To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review. Search Strategy: Literature search conducted in databases from January 1990 till August 2019 using various search terms. Selection Criteria: Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language. Data Collection and Analysis: PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer. Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively. OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.
Spotnitz ME et al., 2020 Obstet Gynecol Open Access
To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users. We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching. Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5-4.0] cases/1,000 person-years and 5.2 [95% CI 3.7-7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16-0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time. Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.
Conz L et al., 2020 Acta Obstet Gynecol Scand
Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed). We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I(2) = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I(2) = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I(2) = 0%, P = .84). Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.
Moradinazar M et al., 2020 Breast Cancer (Dove Med Press) Open Access
Although the use of contraceptive hormones is a risk factor for development of breast cancer, level of risk is unknown; thus the current research was conducted to investigate the effect of factors related to fertility and hormone use on risk of breast cancer in women aged under 50 years old in the west of Iran. In this case-control study, all incidence cases of breast cancer aged between 25-49 years old (n=212) were selected. Twice as many as the case group, the individuals referred to other outpatient sections of the same hospital at the time of study and up to 2 years after the follow-up not diagnosed with breast or other cancers were selected as a control group. The data were collected using healthy fertility program and middle-aged periodical care forms developed by Iran's Ministry of Health (MOH). After controlling for confounding variables, history of hormonal use for contraception (OR=2.02, 95% CI=1.2-3.3) and hormone therapies (OR=1.9, 95% CI=1.2-3.04) were identified as factors increasing the risk of breast cancer. Dose-response relationships between breast cancer and the use of hormones for contraception and hormone therapy indicated that these factors increased the risk of breast cancer. The risk was found to be higher in women who had been under hormone therapy for more than 120 months. With an increase in the age of the first menstruation, risk of breast cancer increased linearly, but with an increase in the age of the first pregnancy, risk of breast cancer increased exponentially. After 20 years of age, the risk increased with a steeper slope. Considering the effect of hormone therapy and fertility factors on breast cancer and changeability of listed risk factors, the researchers suggest planning for sensitizing, increasing the awareness, and educating women and professionals regarding the influence of fertility and hormonal factors including pregnancy at lower ages, minimizing the use of hormones for contraception, and hormone therapy.
Loopik DL et al., 2020 Eur J Cancer Open Access
Hormonal contraceptive use has been associated with the development of cervical cancer, although inconsistent results are reported on the association with intrauterine device (IUD) use. The aim of this study was to evaluate the association between the type of contraceptive use and the development of cervical intraepithelial neoplasia grade III or worse (CIN3+). A retrospective population-based cohort study including women aged 29-44 years attending the cervical cancer screening program with normal cytology between 2005 and 2009 identified from the Dutch Pathology Registry. Subgroups with at least 5 years registered use of an oral contraceptive (OC) or IUD were compared with non-users. Risk ratios of CIN3+ were estimated per contraceptive type. s702,037 women were included with a median follow-up of 9.7 years, of which 6705 (0.96%) and 559 (0.08%) women developed CIN3 and cervical cancer, respectively. IUD use was associated with an increased risk of developing CIN3+ (risk ratio (RR) 1.51, 95% confidence interval (CI) 1.32-1.74), and OC use was associated with an increased risk of developing CIN3+ (RR 2.77, 95%CI 2.65-3.00) and cervical cancer (RR 2.06, 95%CI 1.52-2.79). The risk of developing CIN3+ and cervical cancer was higher for OC users compared with IUD users (RR 1.83, 95%CI 1.60-2.09 and RR 1.70, 95%CI 1.00-2.90, respectively). Both OC use and IUD use were associated with an increased risk of developing CIN3+. However, for women with a contraceptive wish, an IUD seems safer than an OC as the risk of developing CIN3+ and cervical cancer was higher for OC users.
Landersoe SK et al., 2019 Eur J Contracept Reprod Health Care
The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users. This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users. Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) -39.6%, -25.9%; p < 0.001], 35.6% lower among POP users (95% CI -49.0%, -18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI -31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI -35.0%, -25.3%; p < 0.001) and 29.7% lower among POP users (-39.1%, -17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users. Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered.
Kusmiyati Y et al., 2019 Kesmas: National Public Health Journal Open Access
The use of long hormonal contraceptives can disrupt the balance of estrogen in the body, resulting in abnormal cell changes. This study aimed to determine a correlation between the duration of hormonal contraception and risk of cervical cancer. This study used a case-control design. The population were patients who had examined at a cancer installation and obstetrics-gynecology polyclinic Dr. Sardjito Hospital in 2018. Case samples were 95 women have cervical cancer diagnosis and control were 95 women with a negative pap smear. Sampling with random sampling. Dependent variable cervical cancer and independent variable the duration of hormonal contraception are obtained from medical records. Cervical cancer is assessed by doctor’s diagnosis. Data analysis used logistic regression. Results showed that 44.7% of samples used long-term hormonal contraception (over 5 years). Length of use of hormonal contraception had a significant correlation with the incidence of cervical cancer (p-value < 0.01). Hormonal contraceptive use more than 5 years have a risk 4.2 times (95% CI 1.01-5.69) of cervical cancer than using less than 5 years after being controlled with the first marriage age and parity
ACOG, 2019 Obstet Gynecol
Although numerous studies have addressed the safety and effectiveness of hormonal contraceptive use in healthy women, data regarding women with underlying medical conditions or other special circumstances are limited. The U.S. Medical Eligibility Criteria (USMEC) for Contraceptive Use, 2016 (), which has been endorsed by the American College of Obstetricians and Gynecologists, is a published guideline based on the best available evidence and expert opinion to help health care providers better care for women with chronic medical problems who need contraception. The goal of this Practice Bulletin is to explain how to use the USMEC rating system in clinical practice and to specifically discuss the rationale behind the ratings for various medical conditions. Contraception for women with human immunodeficiency virus (HIV) (); the use of emergency contraception in women with medical coexisting medical conditions, including obesity, (); and the effect of depot medroxyprogesterone acetate (DMPA) on bone health () are addressed in other documents from the American College of Obstetricians and Gynecologists.
Goshtasebi A et al., 2019 Clin Endocrinol (Oxf) Open Access
Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. We performed literature searches for prospective published peer-reviewed articles providing 12to 24-month BMD change in adolescent (12to 19-year-old) women using CHC vs CHC-unexposed control women. Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers. Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm(2) in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm(2) in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I(2) were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis. Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.
Keenan L et al., 2018 Linacre Q
Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT. To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews. Selection Criteria: We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies. 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold. Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning. HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between threeand ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.
Harrison D et al., 2018 Linacre Q
The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term "ovulation" to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception. For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.
Hilger DJ et al., 2018 Linacre Q
Since the 1960s, hormonal contraceptives have become the most commonly used method of pregnancy prevention in the United States and the world. Oral contraceptives are used by a large percentage of women, including Christian women. There are known health risks to women demonstrated in research published since Pope Paul VI's prophetic encyclical Humanae vitae in 1968. These risks include venous thrombosis, cardiovascular risks, and an increased risk of cancer. These risks are medically recognized with continued scientific debate on the degree. The risks are significantly increased with preexisting conditions and in certain demographic groups. Discussing known and potential treatment risks is a standard that is both accepted by the medical community and is increasingly expected by patients. This discussion can be accomplished by the mechanism and principle of informed consent. Depending on the circumstances, abstinence or fertility awareness-based methods (FABMs) should be presented to patients. FABMs are licit, safe, and effective methods of pregnancy prevention. Informed consent is the most effective means of providing patients with pertinent information on the significant risks of contraception. This article discusses the use of the informed consent to provide patients with information on the medical and ethical risks of oral contraceptives. FABMs and abstinence are presented as effective, safe, and licit preferences to oral contraceptives. Discussing known and potential treatment risks is accepted by the medical community and expected by patients (shared decision making). The authors discuss the historical context of Pope Paul VI's encyclical Humanae vitae in relationship to the development and rapid adoption of oral contraceptives.
Iversen L et al., 2018 BMJ (Clinical research ed.)
To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer. Prospective, nationwide cohort study. Denmark, 1995-2014. All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.
Peragallo Urrutia R et al., 2018 Obstet Gynecol
To summarize best available prospective data on typical and perfect use effectiveness of fertility awareness-based methods for avoiding pregnancy. We conducted a systematic review of studies published in English, Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. We reviewed 8,755 unique citations and included 53 studies that contained 50 or greater women using a specific fertility awareness-based method to avoid pregnancy, calculated life table pregnancy probabilities or Pearl rates, and prospectively measured pregnancy intentions and outcomes. We systematically evaluated study quality. TABULATION, INTEGRATION, Of 53 included studies, we ranked 0 high quality, 21 moderate quality, and 32 low quality for our question of interest. Among moderate-quality studies, first-year typical use pregnancy rates or probabilities per 100 woman-years varied widely: 11.2-14.1 for the Standard Days Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method, 4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double-check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus Method. First-year perfect use pregnancy rates or probabilities among moderate-quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method, 1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method, 0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor. Studies on the effectiveness of each fertility awareness-based method are few and of low to moderate quality. Pregnancy rates or probabilities varied widely across different fertility awareness-based methods (and in some cases, within method types), even after excluding low-quality studies. Variability across populations studied precludes comparisons across methods.
Fehring RJ et al., 2018 Linacre Q
Brajic TS et al., 2018 J Musculoskelet Neuronal Interact
To assess combined hormonal contraceptives (CHC) use and adolescent women's peak areal bone mineral density (BMD) accrual. We enrolled 527 randomly selected women across Canada (2004-6) divided by age into adolescents (16-19) and young adults (20-24) and by CHC use to ever (E-CHC)/never (N-CHC) users. At baseline and year 2 we measured height, weight, and BMD at lumbar spine (L1-4), femoral neck, and total hip sites. Interviewer-administered questionnaires addressed menarche age, cigarette and alcohol use, calcium/vitamin D intakes, physical activity and estrogen dose (≤30/>30 micrograms). Linear regression models examined associations of CHC use with 2-year BMD change adjusted for bone-related variables. Of 307 women with complete data, 229 (75%) used CHC. N-CHC adolescents gained significantly more unadjusted total hip BMD +0.012 g/cm(2)/2-y (95% C.I.: 0.001, 0.023) with similar trends at all sites. N-CHC adolescents tended to have greater adjusted femoral neck BMD gain: mean difference +0.009 g/cm(2) (95% CI: -0.002; 0.021). In young women N-CHC, however, adjusted femoral neck BMD decreased significantly more -0.021 g/cm(2) (95%CI: -0.006; -0.036) with similar trends at other sites. BMD changes were unrelated to estrogen dose and age at starting CHC. Adolescent CHC users in a random population demonstrated less hip region peak BMD accrual than non-users. This requires randomized control trial confirmation.
White ND, 2018 Am J Lifestyle Med Open Access
Contemporary hormonal contraception formulations contain lower doses of estrogen, have new synthetic progestin components, and provide novel methods of delivery that have not been studied extensively in relation to breast cancer risk. Given that hormonal contraception is the leading method of birth control in the United States, it is important to reevaluate risk using current formulations. Recent studies including contemporary hormonal contraception formulations will be described.
Mørch LS et al., 2017 N Engl J Med
Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).
Roberts TA et al., 2017 Contraception
Studies have demonstrated an association between hormonal contraception use with subsequent depression and antidepressant use. This association has not been assessed among postpartum women. This study is a secondary analysis of insurance records from 75,528 postpartum women enrolled in the US military medical system, who delivered between October 2012 and September 2014. Our analyses excluded women who used antidepressants or had a diagnosis of depression in the 24months prior to delivery. We assessed the relationship of hormonal contraception use with subsequent antidepressant use or diagnosis with depression in the first 12months postpartum using Cox proportional hazards regression, with a time dependent covariate measuring exposure to hormonal contraception. Antidepressants were prescribed to 7.8% of women and 5.0% were diagnosed with depression. In multivariable analysis adjusting for demographics, both antidepressant use and diagnosis with depression were associated with: younger age, lower socioeconomic status, and a history of military service. Compared to women with no hormonal contraceptive use, use of etonogestrel containing contraception was associated with a higher risk of antidepressant use (Implant: adjHR:1.22(95%CI:1.06-1.41), p<0.001; Ring:1.45(1.16-1.80), p=0.001). Use of norethindrone-only pills was associated with a lower risk of antidepressant use (0.58(0.52-0.64), p<0.001) and depression diagnosis (0.56(0.49-0.64), p<0.001). Use of a levonorgestrel intrauterine system was associated with a lower risk of depression diagnoses (0.65(0.52-0.82), p<0.001). The risk of major depression diagnosis and antidepressant use in the postpartum period varies with the type of hormonal contraception used. Further research is required to describe the mechanisms of these relationships.
Fehring RJ et al., 2017 J Obstet Gynecol Neonatal Nurs
To analyze the effectiveness of an online, nurse-managed natural family planning (NFP) program among breastfeeding women and subgroups of these women. Longitudinal comparative cohort study. A university-based online NFP education program and menstrual cycle charting system. Women (N = 816) with a mean age of 30.3 years (standard deviation = 4.5) who registered to use the online NFP system and indicated they were breastfeeding. Participants tracked their fertile times with an electronic hormone fertility monitor (EHFM), cervical mucus monitoring, or both. All unintended pregnancies were evaluated by professional nurses. The correct use pregnancy rates were 3 per 100 users over 12 cycles of use, and typical rates were 14 per 100 at 12 cycles of use. At 12 cycles of use, total pregnancy rates were 16 per 100 for electronic hormone fertility monitor users (n = 380), 81 per 100 among mucus-only users (n = 45), and 14 per 100 for electronic hormone fertility monitor plus mucus users (n = 391). Use of a nurse-managed online NFP program for women can be effective to help women avoid pregnancy while breastfeeding, especially with correct and consistent use.
Lovett JL et al., 2017 Evolution, medicine, and public health
In the evolutionary past, women spent most of their reproductive lives either pregnant or in lactational amenorrhea, and rarely menstruated. The current pattern of frequent menses, and the associated increase in endogenous hormonal exposure, has been implicated in the current breast cancer epidemic. It is not known, however, whether oral contraceptives further increase, or actually decrease, hormonal exposure over one menstrual cycle. Here, we examined variation in hormonal exposure across seven oral contraceptive (OC) formulations, and produced the first quantitative comparison of exogenous versus endogenous hormone exposure. Methodology: Data from 12 studies of serum estradiol (E2) and progesterone (P4) were aggregated to create a composite graph of endogenous hormone levels over one menstrual cycle in European or American women (age 19-40 years). Pharmacokinetic package insert data, also from Western women, were used to calculate exposures for hormones in seven different OC formulations. Endogenous and exogenous hormone levels were compared after adjusting for the relative binding affinity (RBA) of progestin to the progesterone receptor and ethinyl estradiol (EE) to the estrogen receptor. After adjusting for RBA, median ethinyl estradiol exposure across 28 days in the OCs was 11.4 nmol/l, similar to median E2 exposure. One formulation, however, was 40% higher in ethinyl estradiol exposure relative to median endogenous estradiol. Median exposure from progestins in OCs (1496 nmol/l) was 4-fold higher than the median endogenous exposure from P4 (364 nmol/l). Exposure from OC progestins ranged from one sixtieth to 8-fold median endogenous P4 over 28 days. Conclusions and Given that breast cancer risk increases with hormonal exposure, our finding that four widely prescribed formulations more than quadruple progestin exposure relative to endogenous progesterone exposure is cause for concern. As not all formulations produce the same exposures, these findings are pertinent to contraceptive choice. We also identify critical gaps in the provision of relevant data on pharmacokinetics and carcinogenicity by drug manufacturers.
Kyvernitakis I et al., 2017 Osteoporos Int
There has been concerning about women receiving depot medroxyprogesterone acetate (DMPA) contraception because of the prolonged hypoestrogenemic state regarding the potential negative effects on bone health. This study showed that DMPA exposure is associated with increased fracture risk and that fracture risk increases with longer DMPA exposure. DMPA has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. We performed this large population-based study to assess the association between use of DMPA or combined oral contraceptives and the incident risk of fracture. We identified 4189 women between 20 and 44 years of age with a first-time fracture diagnosis, matched them with 4189 random controls using the Disease Analyzer database and investigated the relation with DMPA exposure. Overall, 11 % of the fracture cases and 7.7 % of the controls had DMPA use recorded. The adjusted OR for developing a fracture in patients with current use of DMPA compared to non-users was 0.97 (95 % CI 0.51-1.86), 2.41 (95 % CI 1.42-4.08), and 1.46 (95 % CI 0.96-2.23) for 1-2, 3-9, and ≥10 prescriptions, respectively. The adjusted OR for developing a fracture in patients with past use of DMPA compared to non-users was 0.96 (95 % CI 0.73-1.26), 1.14 (95 % CI 0.86-1.51), and 1.55 (95 % CI 1.07-2.27) for 1-2, 3-9, and ≥10 prescriptions, respectively. The highest fracture risk was identified in young patients less than 30 years with longer DMPA exposure (≥10 prescriptions; OR 3.04, 95 % CI 1.36-6.81), as well as in patients in the late reproductive years with past use of DMPA (OR 1.72, 95 % CI 1.13-2.63). Our results indicate that DMPA exposure is associated with increased fracture risk and may have negative effects on bone metabolism, resulting in impaired bone mineral acquisition during adolescence and accelerated bone loss in adult life.
Fehring RJ et al., 2016 MCN Am J Matern Child Nurs
The aims of this study were to determine and compare extended use-effectiveness of an online nurse-managed fertility education service program among women (and subgroups of women) seeking to avoid pregnancy. This was a 24-month prospective study of a university-based online Web site with 663 nonbreastfeeding women using an online charting system to avoid pregnancy. Participants tracked their fertility online with either cervical mucus monitoring, electronic hormonal fertility monitoring, or both fertility indicators. Unintended pregnancies were validated by professional nurses. Participants had a mean age of 30.4 years (SD = 6.3) and mean 1.7 children (SD = 2.0). Among the 663 nonbreastfeeding participants there were 2 unintended pregnancies per 100 at 24 cycles of correct use and 15 pregnancies at 24 cycles of typical use. However, the 212 women using the electronic fertility monitor had a typical use unintended pregnancy rate of 6 at 24 cycles of use in comparison with the 118 women using cervical mucus monitoring that had a typical use pregnancy rate of 19 at 24 cycles and with the 333 women using both fertility indicators that had a pregnancy rate of 18 at 24 cycles of use. CLINICAL Use of the fertility monitor to estimate fertility among nonbreastfeeding women provides the most secure method of avoiding pregnancy.
Samson ME et al., 2016 Maturitas Open Access
Oral contraceptive pills have been implicated in the pathophysiology of breast cancer. Although many studies have examined the relationship between combined oral contraceptives (COCs) and breast cancer, there is a paucity of literature that discusses progestin-only oral contraceptives (POCs) and breast cancer. The purpose of this investigation is to examine potential associations between different types of oral contraceptives and breast cancer mortality in the South Carolina Medicaid population among different racial/ethnic groups. Subjects included 4816 women diagnosed with breast cancer between 2000 and 2013. Kaplan-Meier curves were calculated to determine time-to-mortality rates among users of oral contraceptives. Competing-risks models and Cox multivariate survival models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer and other-cause mortality, as well as all-cause mortality. POCs were associated with a significantly decreased risk of breast cancer mortality (HR: 0.07; 95% CI: 0.01, 0.52) and a non-significant increased risk of all-cause mortality (HR: 1.04; 95% CI: 0.52, 2.07). COCs increased the risk of breast cancer mortality (HR: 1.61; 95% CI: 1.14, 2.28) and all-cause mortality (HR: 1.83; 95% CI: 1.30, 2.57). Use of POCs may be associated with a decreased risk of breast cancer mortality. Due to the small sample size of POC users in the current study, additional research is needed to confirm these findings.
Peck R et al., 2016 Linacre Q
Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.
Prior JC, 2016 Women's Reproductive Health
Here I respond to Akers, Dhar, and Shah's (2016), Stubbs's (2016), Olshansky's (2016), and Kissling's (2016) commentaries on the article (Prior, 2016) in which I expressed concerns about the potential adverse long-term reproductive and bone health effects on normal adolescents’ maturation related to use of combined hormonal contraceptives (CHC) for contraception and/or treatment. Although Akers et al. (2016) take exception, the precautionary principle on which medical/pharmaceutical ethics is based challenges us to show that CHC is officially indicated and effective in randomized, double-blind, placebo-controlled trials with adolescents. Those who support current practices are obligated to provide young patients and their parents with evidence from large, population-based, prospective studies (or meta-analyses of longitudinal data) that adolescents who have used CHC develop the same menstrual cycle/ovulatory function, fertility, and reproductive lifespan and similar bone density and strength as peers who did not use CHC. Without this information there can be neither reproductive justice (Kissing, 2016), nor true choice. Why is this minimal, expected scientific data not available? It is likely that authors of practice guidelines for adolescent CHC contraceptive use and who advocate its “non-contraceptive benefits” have pro-estrogen cultural biases or conflicts of interests due to pharmaceutical industry connections. I agree with Olshansky (2016) that we should listen to adolescents’ concerns and use evidence-based and safe treatments for milder heavy bleeding and cramps. For heterosexual adolescents seeking contraception, we can suggest and explain the use of safer, yet effective, nonhormonal strategies, such as the copper IUD or a barrier plus full-dose vaginal spermicide.
Singata-Madliki M et al., 2016 J Fam Plann Reprod Health Care
Depot medroxyprogesterone acetate (DMPA) is the most commonly used hormonal contraceptive method in South Africa. It is frequently administered in the immediate postnatal period, yet it is unclear whether it affects the risk of postnatal depression (PND). To determine whether DMPA increases the risk of PND compared with the copper-containing intrauterine device (IUD) when administered after delivery. DESIGN AND A single-blind randomised controlled trial conducted at two teaching hospitals in East London, South Africa. Eligible, consenting women (N=242) requiring postnatal contraception were randomised to receive DMPA or an IUD within 48 hours of childbirth and interviewed at 1 and 3 months postpartum. Depression was measured using the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS). Resumption of sexual intercourse, menstrual symptoms and breastfeeding rates were also assessed. One-month EPDS depression scores were statistically significantly higher in the DMPA arm compared with IUD arm (p=0.04). Three-month BDI-II scores were significantly higher in the DMPA arm than in the IUD arm (p=0.002) and, according to the BDI-II but not the EPDS, more women in the DMPA arm had major depression at this time-point (8 vs 2; p=0.05). There were no statistically significant differences in other outcome measures except that fewer women had resumed sexual activity by 1 month postpartum in the DMPA arm (13% vs 26%; p=0.02). The possibility that immediate postnatal DMPA use is associated with depression cannot be excluded. These findings justify further research with longer follow-up. PACTR201209000419241.
Roura E et al., 2016 PLoS One Open Access
In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and findingsWe followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Heikkinen S et al., 2015 Cancer Causes Control
Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data. The survey 'Women's Health and Use of Hormones' was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys. We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10-1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (≥2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12-1.68) for premenopausal and 1.11 (95 % CI 1.03-1.20) for postmenopausal women, when compared to never-users of other HC. Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.
Birch Petersen K et al., 2015 Hum Reprod
To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users. AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. STUDY DESIGN, SIZE, A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC. OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan. The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests. The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).
ACOG, 2015 Obstet Gynecol
Emergency contraception, also known as postcoital contraception, is therapy used to prevent pregnancy after an unprotected or inadequately protected act of sexual intercourse. Common indications for emergency contraception include contraceptive failure (eg, condom breakage or missed doses of oral contraceptives) and failure to use any form of contraception (1-3). Although oral emergency contraception was first described in the medical literature in the 1960s, the U.S. Food and Drug Administration (FDA) approved the first dedicated product for emergency contraception in 1998. Since then, several new products have been introduced. Methods of emergency contraception include oral administration of combined estrogen-progestin, progestin only, or selective progesterone receptor modulators and insertion of a copper intrauterine device (IUD). Many women are unaware of the existence of emergency contraception, misunderstand its use and safety, or do not use it when a need arises (4-6). The purpose of this Practice Bulletin is to review the evidence for the efficacy and safety of available methods of emergency contraception and to increase awareness of these methods among obstetrician-gynecologists and other gynecologic providers.
Fehring RJ et al., 2015 J Midwifery Womens Health
The length of periodic abstinence, due to overestimation of the fertile phase of the menstrual cycle, is often a cause for dissatisfaction, discontinuation, and user error with natural family planning (NFP) methods. The objective of this research was to compare the length of required abstinence (ie, estimated fertility) and coital frequency between 2 NFP methods. This was an analysis of data from a 12-month prospective comparison study in which participants were randomized into either an electronic hormonal fertility monitor (EHFM) group or a cervical mucus monitoring (CMM) group-both of which included a fertility algorithm as a double check for the beginning and end of the estimated fertile window. The number of days of estimated fertility and coitus was extracted from each menstrual cycle of data, and t tests were used to compare the means of these 2 variables between the 2 NFP methods. The study involved 197 women (mean [SD] age 29.7 [5.4]) who used the EHFM to estimate the fertile window and 160 women (mean [SD] age 30.4 [5.3]) who used CMM to estimate the fertile window. They produced 1,669 menstrual cycles of data. After 12 months of use, the EHFM group had statistically fewer days of estimated fertility than the CMM group (mean [SD] days, 13.25 [2.79] vs 13.68 [2.99], respectively; t = 2.07; P = .039) and significantly more coitus (mean [SD] coital acts, 4.22 [3.16] vs 4.05 [2.88], respectively; t = 1.17; P = .026). The use of the EHFM seems to provide more objectivity and confidence in self-estimating the fertile window and using nonfertile days for intercourse when avoiding pregnancy.
Lopez LM et al., 2015 Cochrane Database Syst Rev Open Access
Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life. We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women. Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports. Selection Criteria: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture. Data Collection and Analysis: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis. MAIN We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use. AUTHORS' Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.
Ichida M et al., 2015 Asian Pac J Cancer Prev Open Access
Low-dose oral contraceptives (OC) were approved by the Japanese Ministry of Health, Labor and Welfare in 1999, yet despite their contraceptive and non-contraceptive health benefits, only 5% of the target population use them. Fear of increased cancer risk, particularly breast cancer, is one reason for this. Due to low OC uptake and low screening participation, a paucity of data is available on the risk of OC use and breast cancer in Japanese women. The present study investigated OC use and breast cancer risk, as well as menstrual, reproductive and family factors. This was a clinic-based case-control study of women aged 20-69yrs who had undergone breast screening between January 2007 and December 2013 in central Tokyo. In all, 28.8% of the participants had experience with OC use. Cases were 155 women with a pathologically confirmed diagnosis of breast cancer. Controls were the remaining 12,333 women. Increased age was a significant risk factor for breast cancer (p<0.001). A lower risk was found in premenopausal women presently taking OC compared to never users (OR 0.45; 95% CI 0.22-0.90) after adjusting for age, parity and breast feeding, and a family history of breast cancer. Increased age rather than OC use had a greater effect on breast cancer risk. This risk may be decreased in premenopausal women with OC use, but further long-term prospective studies are necessary.
Kahlenborn C et al., 2015 Linacre Q
There has been much debate regarding levonorgestrel emergency contraception's (LNG-EC's) method of action since 1999 when the Food and Drug Administration first approved its use. Proponents of LNG-EC have argued that they have moral certitude that LNG-EC works via a non-abortifacient mechanism of action, and claim that all the major scientific and medical data consistently support this hypothesis. However, newer medical data serve to undermine the consistency of the non-abortifacient hypothesis and instead support the hypothesis that preovulatory administration of LNG-EC has significant potential to work via abortion. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room protocols. In the future, technology such as the use of early pregnancy factor may have the potential to quantify how frequently preovulatory LNG-EC works via abortion. Lay How Plan B (levonorgestrel emergency contraception) works has been vigorously debated ever since the Food and Drug Administration approved it in 1999. Many doctors and researchers claim that it has either no-or at most-an extremely small chance of working via abortion. However, the latest scientific and medical evidence now demonstrates that levonorgestrel emergency contraception theoretically works via abortion quite often. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room rape protocols.
Bethea TN et al., 2015 Breast Cancer Res Open Access
Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse. We investigated recency and duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables. OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ERbreast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-. Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ERbreast cancer, is needed.
Beaber EF et al., 2014 Cancer Res
Previous studies of oral contraceptives and breast cancer indicate that recent use slightly increases risk, but most studies relied on self-reported use and did not examine contemporary oral contraceptive formulations. This nested case-control study was among female enrollees in a large U.S. integrated health care delivery system. Cases were 1,102 women ages 20 to 49 years diagnosed with invasive breast cancer from 1990 to 2009. Controls were randomly sampled from enrollment records (n = 21,952) and matched to cases on age, year, enrollment length, and medical chart availability. Detailed oral contraceptive use information was ascertained from electronic pharmacy records and analyzed using conditional logistic regression, ORs, and 95% confidence intervals (CI). Recent oral contraceptive use (within the prior year) was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.3-1.9) relative to never or former OC use. The association was stronger for estrogen receptor-positive (ER(+); OR, 1.7; 95% CI, 1.3-2.1) than estrogen receptor-negative (ER(-)) disease (OR, 1.2, 95% CI, 0.8-1.8), although not statistically significantly different (P = 0.15). Recent use of oral contraceptives involving high-dose estrogen (OR, 2.7; 95% CI, 1.1-6.2), ethynodiol diacetate (OR, 2.6; 95% CI, 1.4-4.7), or triphasic dosing with an average of 0.75 mg of norethindrone (OR, 3.1; 95% CI, 1.9-5.1; Pheterogeneity compared with using other oral contraceptives = 0.004) was associated with particularly elevated risks, whereas other types, including low-dose estrogen oral contraceptives, were not (OR, 1.0; 95% CI, 0.6-1.7). Our results suggest that recent use of contemporary oral contraceptives is associated with an increased breast cancer risk, which may vary by formulation. If confirmed, consideration of the breast cancer risk associated with different oral contraceptive types could impact discussions weighing recognized health benefits and potential risks.
Cortés ME et al., 2014 The Linacre quarterly Open Access
A number of side effects have been linked to the use of hormonal contraceptives, among others, alterations in glucose levels. Hence, the objective of this mini-review is to show the main effects of hormonal contraceptive intake on glycemic regulation. First, the most relevant studies on this topic are described, then the mechanisms that might be accountable for this glycemic regulation impairment as exerted by hormonal contraceptives are discussed. Finally, we briefly discuss the ethical responsibility of health professionals to inform about the potential risks on glycemic homeostasis regarding hormonal contraceptive intake.
Soini T et al., 2014 Obstet Gynecol
To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. All Finnish women aged 30-49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994-2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35-0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05-0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45-0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28-0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49-0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13-1.25; 1,542 observed compared with 1,292 expected cases). The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer. II.
Leslie HH et al., 2014 PLoS One Open Access
To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.
Raviele KM, 2014 Linacre Q
The Ethical and Religious Directives for Catholic Health Care Services allows the use of an emergency contraceptive for a woman who has been raped, as a defense against her attacker's sperm, provided the drug prevents fertilization and does not act against a conceived human life. Catholic emergency rooms around the country have been pressured to provide Plan B (LNG-EC) to patients seeking help after a sexual assault. Catholic bioethicists have supported the use of this drug based on their interpretation of the scientific literature regarding its mechanism of action. This paper presents a review of the mechanisms of action of LNG-EC when given during the fertile window, showing a high probability that it acts against human life rather than preventing fertilization, and proposes another class of drugs as a possible alternative.
Govender Y et al., 2014 PLoS One Open Access
Clinical studies suggest that the injectable contraceptive medroxyprogesterone acetate (MPA) increases susceptibility to infections such as HIV-1, unlike the injectable contraceptive norethisterone enanthate (NET-EN). We investigated the differential effects, molecular mechanism of action and steroid receptor involvement in gene expression by MPA as compared to NET and progesterone (P4) in the End1/E6E7 cell line model for the endocervical epithelium, a key point of entry for pathogens in the female genital mucosa. MPA, unlike NET-acetate (NET-A) and P4, increases mRNA expression of the anti-inflammatory GILZ and IκBα genes. Similarly, MPA unlike NET-A, decreases mRNA expression of the pro-inflammatory IL-6, IL-8 and RANTES genes, and IL-6 and IL-8 protein levels. The predominant steroid receptor expressed in the End1/E6E7 and primary endocervical epithelial cells is the glucocorticoid receptor (GR), and GR knockdown experiments show that the anti-inflammatory effects of MPA are mediated by the GR. Chromatin-immunoprecipitation results suggest that MPA, unlike NET-A and P4, represses pro-inflammatory cytokine gene expression in cervical epithelial cells via a mechanism involving recruitment of the GR to cytokine gene promoters, like the GR agonist dexamethasone. This is at least in part consistent with direct effects on transcription, without a requirement for new protein synthesis. Dose response analysis shows that MPA has a potency of ∼ 24 nM for transactivation of the anti-inflammatory GILZ gene and ∼ 4-20 nM for repression of the pro-inflammatory genes, suggesting that these effects are likely to be relevant at injectable contraceptive doses of MPA. These findings suggest that in the context of the genital mucosa, these GR-mediated glucocorticoid-like effects of MPA in cervical epithelial cells are likely to play a critical role in discriminating between the effects on inflammation caused by different progestins and P4 and hence susceptibility to genital infections, given the predominant expression of the GR in primary endocervical epithelial cells.
Beaber EF et al., 2014 Cancer Epidemiol Biomarkers Prev Open Access
Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized. We conducted a population-based case-control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle-Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Lifetime duration of OC use for ≥ 15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1-2.2). Current OC use (within 1 year of reference date) for ≥ 5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1-2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor-negative (ER(-)) and triple-negative breast cancer (current use for ≥ 5 years among ages 20-39: ER(-) OR, 3.5; 95% CI, 1.3-9.0; triple-negative OR, 3.7; 95% CI, 1.2-11.8), although differences between groups were not statistically significant. Long-term use of contemporary OCs and current use for ≥ 5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER(-) and triple-negative breast cancer, but these findings require confirmation. Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve.
Poosari A et al., 2014 J Epidemiol Open Access
Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women. A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65-2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral contraception: HR = 1.35, 95% CI, 0.65-2.78; injection contraception: HR = 1.25, 95% CI, 0.56-2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer. There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.
Kotsopoulos J et al., 2014 Breast Cancer Res Treat
It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
Zimmerman Y et al., 2014 Human reproduction update
BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T. A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T. A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18-40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20-25 µg EE had similar effects on total and free T compared with COCs with 30-35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20-25 µg EE) were found to have less impact on SHBG concentrations. The current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated.
Yu A et al., 2013 J Hypertens
Over 100 million women currently use oral contraceptive pills (OCPs) worldwide. However, little is known about the effects of OCPs on arterial stiffness and hemodynamics. Furthermore, whether arterial stiffness and hemodynamics vary throughout the natural menstrual cycle remains controversial. Herein, we estimated the effect of the natural menstrual cycle and OCP use on arterial stiffness and hemodynamics. Healthy, nonsmoking women, aged 18-30 years, were recruited if they had regular menstrual cycles and never used OCPs (OCP nonuser group), or were using low-dose OCPs for at least 6 months (OCP user group). Using applanation tonometry, three assessments of arterial stiffness and central and peripheral hemodynamics were performed in a randomized order: during the early follicular (days 3-6), late follicular (days 14-16), and luteal (days 22-26) phases. Within group and between group comparisons were performed using general linear models. Sixty women (21.7 ± 2.8 years) were recruited. Compared with OCP nonusers, OCP users had significantly increased aortic and peripheral SBPs during the active OCP use, but not during the inert tablet phase. No differences in arterial stiffness were noted. OCP use was associated with significant increases in aortic and peripheral blood pressures, but not with increased arterial stiffness. Given the widespread OCP use, future longitudinal studies are needed to confirm our findings and assess the long-term effect of OCPs on arterial stiffness and hemodynamics.
Thurmond AS, 2013 Seminars in Interventional Radiology Open Access
Fallopian tube catheterization is used for treatment of infertility caused by proximal tubal occlusion, and has replaced surgical treatment for this condition. More recently, fallopian tube catheterization has been used for tubal sterilization. Interventional radiologists tested numerous methods for tubal occlusion using the rabbit as an animal model. As a result, a tubal device has recently been Food and Drug Administration approved for permanent sterilization using hysteroscopic guidance; it can also be placed fluoroscopically by fallopian tube catheterization as an "off-label" procedure. This is a 5-year continuation and update on a procedure that has been done by interventional radiologists for 25 years; history of the development of fallopian tube catheterization in women has been published in detail in this journal. Highlighted in this article will be description of the basic components needed for fallopian tube catheterization.
Cobey KD et al., 2013 Biological psychology
The purpose of this study was to test whether men perceive changes in their female partner's attractiveness as a function of her fertility status. We further tested how both male and female self-perception varies in relation to female fertility status. This study benefits from the use of transvaginal ultrasonography to detect fertility during the regular cycle and the use of a within-subjects design in which romantic couples were followed both across the cycle and during hormonal contraceptive use. We find that men rated their female partner as more attractive near to ovulation (when fertile) as compared to during the luteal cycle phase or during hormonal contraceptive use. Moreover, our results point to a presently unrecognized negative consequence of hormonal contraceptive use on male self-perception, with men rating themselves lower in attractiveness when their partner was using hormonal contraceptives than when she was regularly cycling. In contrast, there was no difference across measures in female self-reported attractiveness. Results are discussed in terms of their potential impact on within-couple social dynamics.
Moorman PG et al., 2013 J Clin Oncol
To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.
Fehring RJ et al., 2012 Contraception Open Access
The aim was to compare the efficacy and acceptability of two Internet-supported fertility-awareness-based methods of family planning. Six hundred and sixty-seven women and their male partners were randomized into either an electronic hormonal fertility monitor (EHFM) group or a cervical mucus monitoring (CMM) group. Both groups utilized a Web site with instructions, charts and support. Acceptability was assessed online at 1, 3 and 6 months. Pregnancy rates were determined by survival analysis. The EHFM participants (N=197) had a total pregnancy rate of 7 per 100 users over 12 months of use compared with 18.5 for the CMM group (N=164). The log rank survival test showed a significant difference (p<.01) in survival functions. Mean acceptability for both groups increased significantly over time (p<.0001). Continuation rates at 12 months were 40.6% for the monitor group and 36.6% for the mucus group. In comparison with the CMM, the EHFM method of family planning was more effective. All users had an increase in acceptability over time. Results are tempered by the high dropout rate.
Zhu H et al., 2012 Eur J Contracept Reprod Health Care
It has been suggested that taking oral contraceptives (OCs) may increase breast cancer incidence. However, data in this regard are inconsistent. We performed this meta-analysis to estimate the association between OC use and breast cancer risk. Prospective cohort studies on OC use and breast cancer risk were identified by searching databases from the period 1960 to 2012. Results from individual studies were synthetically combined using STATA 11 software. A total of 13 prospective cohort studies were included in our meta-analysis, involving 11,722 cases and 859,894 participants. The combined relative risk (RR) of breast cancer for evercompared with never-OC users was 1.08 (95% confidence interval [CI]: 0.99-1.17). Dose-response analysis based on five eligible studies showed that every ten-years' increment of OC use was associated with a significant 14% (95% CI: 1.05-1.23) rise in breast cancer risk. Little evidence of publication bias was found. This meta-analysis provides evidence of a non-significant increase in breast cancer risk associated with ever OC use, but the risk for long-term OC users is significantly greater. However, the latter finding is based on only a limited number of studies.
Cibula D et al., 2012 European journal of endocrinology
The aim was to evaluate changes of bone mineral density (BMD) and markers of bone turnover in healthy adolescents, and in adolescent users of combined oral contraceptives (COCs) with different ethinylestradiol (EE) contents. In this prospective crossover study, 56 healthy females (15-19.5 years) with desire to use hormonal contraception were randomized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order. Nonusers of the same age (n=28) served as controls. BMD at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months. In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). In the crossover design, a difference between the low- and very low-dose COC users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months. Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC, especially those containing very low dose of EE.
De Seta F et al., 2012 Contraception
The sector of the market that deals with contraception offers a long list of different contraceptive methods. Within the estroprogestinic choice, the routes of administration are oral, transdermic and vaginal one. Even though efficacy is comparable with these methods, secondary and adverse effects are directly involved in the acceptability of the method. This was a prospective comparative study. During 1 year, we enrolled 60 asymptomatic women who voluntarily requested combined oral contraception (COC) or combined contraceptive vaginal ring (CCVR group). After a baseline study of vaginal milieu prior to starting hormonal contraception, we performed a follow-up. For each woman, we examined vaginal pH; quantification of leukocytes, lactobacilli, Candida and cocci on saline microscopy fluid; Gram stain with Nugent score and the presence of vaginal infection [culture for Trichomonas vaginalis, albicans and nonalbicans Candida, Group B Streptococcus (GBS)]. At the end of follow-up, there was a little change of vaginal milieu in both groups. We noted an increase of lactobacilli in the CCVR users and an increase of GBS in COC users. CCVR compared to COC users showed an increase of the number of lactobacilli in vaginal flora. It means that an increase of leukorrhea in that group could be protective in terms of prevention of vaginal imbalance/infection.
Sacco S et al., 2012 The journal of headache and pain
Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives.
Li CI et al., 2012 Cancer Res Open Access
Depo-medroxyprogesterone acetate (DMPA) is an injectable contraceptive that contains the same progestin as the menopausal hormone therapy regimen found to increase breast cancer risk among postmenopausal women in the Women's Health Initiative clinical trial. However, few studies have evaluated the relationship between DMPA use and breast cancer risk. Here, we conducted a population-based case-control study among 1,028 women ages 20 to 44 years to assess the association between DMPA use and breast cancer risk. Detailed information on DMPA use and other relevant covariates was obtained through structured interviewer-administered in-person questionnaires, and unconditional logistic regression was used to evaluate associations between various aspects of DMPA use and breast cancer risk. We found that recent DMPA use for 12 months or longer was associated with a 2.2-fold [95% confidence interval (CI), 1.2-4.2] increased risk of invasive breast cancer. This risk did not vary appreciably by tumor stage, size, hormone receptor expression, or histologic subtype. Although breast cancer is rare among young women and the elevated risk of breast cancer associated with DMPA appears to dissipate after discontinuation of use, our findings emphasize the importance of identifying the potential risks associated with specific forms of contraceptives given the number of available alternatives.
Peck R et al., 2012 Linacre Q Open Access
Pregnancy is not a disease. But more fundamentally, neither is human fertility. They are normal physiologic processes of the sexually mature person. By classifying pregnancy and fertility as disease states, certain entities are able to position contraception as "the cure." Currently, these same organizations want to include oral contraceptive counseling and medications in the new national health-care plan under a preventive care mandate. But it is the physician's role to counsel patients on preventive care measures. We understand that these evidenced-based screenings help to change risky behaviors and catch disease in its earliest stages, thereby reducing patients' overall morbidity and mortality. However, we believe that patients incur substantial health risks when choosing oral contraceptives (OCPs). This paper reviews the major risks of OCPs. The authors presume that the prevailing widespread acceptance and promotion of OCPs indicates general agreement within the medical community that OCPs are good for the patient (or at least not significantly harmful). Therefore, this paper concentrates on the studies which show increased harm and risk to the patient choosing to use OCPs. We have concentrated our efforts on three major areas: increased rates of cardiovascular disease, breast cancer, and human papillomavirus (HPV) or cervical cancer. If fertility and pregnancy are not disease states, and are, in fact, normal conditions associated with healthy individuals, OCPs fail the most important test of preventive medicine: they increase risk of disease instead of decreasing it. Patients should not be misled or confused into believing that what they are taking is "good for them" and is of the same beneficial effect as other preventive measures.
Parkin DM, 2011 Br J Cancer Open Access
The International Agency for Research on Cancer (IARC) Monographs on the carcinogenic risk to humans concluded that combined oral oestrogen–progestogen contraceptives are carcinogenic to humans (IARC, 2007). This evaluation was made on the basis of increased risks for cancer of the breast (among current and recent users only), cervix and liver (in populations that are at low risk for hepatitis B viral infection). There is also convincing evidence in humans that these agents confer a protective effect against cancer of the endometrium and ovary.
Noé G et al., 2011 Contraception
The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates. In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation. For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days -5 to -1), 16 pregnancies were expected and no pregnancy occurred (p<.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods. The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient.
Chapron C et al., 2011 Human reproduction (Oxford, England)
The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.
Ferris R, 2011 Linacre Q
In current medical practice, many women are prescribed hormonal contraceptives as a method of family planning. Over the years, medical professionals have prescribed hormonal contraceptives to manage numerous health conditions in addition to family planning purposes. A particular question arises in regard to women taking hormonal contraceptives for therapeutic reasons if the drug has a contraceptive effect and abortifacient properties. An important consideration is a definite lack of knowledge among medical professionals and patients about alternatives to hormonal contraceptives. To most lay people and medical professionals, fertility awareness-based methods equate to the outdated calendar rhythm method and therefore tend to be regarded as mostly a matter of chance so that they would have no benefit in helping manage gynecological conditions. In this paper, one will be able to see that modern fertility awareness-based methods are effective as a method of family planning and that there are medical applications that offer an excellent alternative in the treatment of various gynecological conditions, including infertility.
Wei S et al., 2011 Contraception Open Access
The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial. A cross-sectional study of 491 women aged 50-80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry. Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5-10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.94). Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.
Memon S et al., 2011 Contraception
Several studies, including an earlier analysis from the Royal College of General Practitioners (RCGP) Oral Contraception Study, have suggested that ever users of oral contraceptives have an increased risk of fracture when compared with never users. In this paper, we examined a subset of women in the RCGP study living in Scotland to determine whether this risk has persisted. A nested case-control study was carried out using data collected prospectively for the RCGP Oral Contraception Study. Cases were women with a first ever diagnosis of fracture (n=651), age-matched to two controls (n=1302). Adjustments were made for smoking, social class and parity. There was not a significant association between ever use of oral contraception and fracture (adjusted odds ratio 1.05, 95% confidence interval 0.86-1.29), compared with never users. Neither were significant associations found between fracture and smoking, social class and parity. The findings did not vary materially with age or type of fracture. Ever use of oral contraception was not associated with fracture in this study.
Nassaralla CL et al., 2011 J Womens Health (Larchmt)
Menstrual cycle function may continue to be altered after discontinuation of oral contraceptives (OC). Few studies have been published on the effects of recent OC use on menstrual cycle parameters; none have examined characteristics of the menstrual flow or the quality of cervical mucus. The purpose of this retrospective matched cohort study is to assess biomarkers of the menstrual cycle after discontinuation of OCs. Among a sample of women who daily recorded observations of menstrual cycle biomarkers, 70 women who had recently discontinued OCs were randomly matched by age and parity with 70 women who had not used OCs for at least 1 year. Outcomes investigated included overall cycle length, length of the luteal phase, estimated day of ovulation, duration of menstrual flow, menstrual intensity, and mucus score. Differences between recent OC users and controls were assessed using random effects modeling. Recent OC users had statistically significantly lower scores for mucus quality for cycles 1 and 2. Additionally, OC users had a later estimated day of ovulation that was statistically significant in cycle 2 and a decreased intensity of menstrual flow that was significant in the first four cycles (difference = -0.48 days). In random effects modeling, all these parameters were significantly different for the first six cycles combined. Menstrual cycle biomarkers are altered for at least two cycles after discontinuation of OCs, and this may help explain the temporary decrease in fecundity associated with recent OC use.
Hunter DJ et al., 2010 Cancer Epidemiol Biomarkers Prev Open Access
Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear. We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001. During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001). Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk. Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.
Rosenberg L et al., 2010 Cancer Epidemiol Biomarkers Prev Open Access
Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor-negative (ER(-)) than with ER-positive (ER(+)) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African American women, a group disproportionately affected by ER(-) cancer. We followed 53,848 Black Women's Health Study participants from 1995 to 2007 through biennial health questionnaires, in which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRR) with 95% confidence intervals (95% CI) were derived from Cox regression models with control for confounding factors. Ever use of oral contraceptives was more strongly associated with ER(-)PR(-) breast cancer (279 cases; IRR, 1.65; 95% CI, 1.19-2.30) than with ER(+)PR(+) cancer (386 cases; IRR, 1.11; 95% CI, 0.86-1.42). The risk of ER(-)PR(-) breast cancer increased with increasing duration of use among recent users. These results indicate that the oral contraceptive formulations used in recent decades increase breast cancer risk in African American women, with a greater effect for ER(-) than ER(+) cancer. Mechanisms to explain the adverse influence of oral contraceptive use on ER(-) breast cancer need to be elucidated.
ACOG, 2009 Obstet Gynecol
Patients are often unaware of the non-contraceptive benefits of hormonal contraception. and this represents an opportunity for counseling (2). A brief list of some common non-contraceptive benefits is provided in Box I. Most hormonal contraceptives combine progestin for its contraceptive effects and an estrogen to stabilize the endometrium and reduce unwanted spocane. Users progestin-only hormonal contraceptives avoid the sile citects associated with the use of contraceptives containing estrogen. Progestin-only contraceptives often can be used in women when estrogen is contraindicated; however, unpredictable spotting may be problematic for some patients. Over time, this unwanted bleeding generally subsides and progestin-only methods may provide highly effective long-term contraception. Since oral contraceptives containing 150 micrograms or mestranol were introduced in ryo0, the dose of estrogen per pill has been reduced: current bills may. . .
Fehring RJ et al., 2009 J Reprod Med
To determine if an electronic hormonal fertility monitor aided method (EHFM) of family planning is more effective than a cervical mucus only method (CMM) in helping couples to avoid pregnancy. Six hundred twenty-eight women were taught how to avoid pregnancy with either the EHFM (n=313) or the CMM (n = 315). Both methods involved standardized group teaching and individual follow-up. All pregnancies were reviewed and classified by health professionals. Correct use and total unintended pregnancy rates over 12 months of use were determined by survival analysis. Comparisons of unintended pregnancies between the 2 methods were made by use of the Fisher exact test. There were a total of 28 unintended pregnancies with the EFHM and 41 with the CMM. The 12-month correct use pregnancy rate of the monitor-aided method was 2.0%, and the total pregnancy rate was 12.0%. In comparison, the 12-month correct use pregnancy rate of the CMM was 3.0%, and the total pregnancy rate was 23.0%. There was a significant difference in total pregnancies between the 2 groups (p<0.05). EFHM is more effective than CMM. Further research is needed to verify the results.
Rosenberg L et al., 2008 Am J Epidemiol Open Access
Oral contraceptive (OC) use has been linked to increased risk of breast cancer, largely on the basis of studies conducted before 1990. In the Case-Control Surveillance Study, a US hospital-based case-control study of medication use and cancer, the authors assessed the relation of OC use to breast cancer risk among 907 case women with incident invasive breast cancer (731 white, 176 black) and 1,711 controls (1,152 white, 559 black) interviewed from 1993 to 2007. They evaluated whether the association differed by ethnicity or tumor hormone receptor status. After control for breast cancer risk factors, the multivariable odds ratio for 1 year or more of OC use, relative to less than 1 year of use, was 1.5 (95% confidence interval: 1.2, 1.8). The estimates were similar within age strata (<50 years and >or= 50 years). The odds ratios were larger for use within the previous 10 years, long-duration use, and black ethnicity, but these differences were not statistically significant. The association of OC use with breast cancer risk did not differ according to the estrogen or progestogen receptor status of the tumor. These results suggest that OC use is associated with an increased risk of breast cancer diagnosed in recent years.
Vestergaard P et al., 2008 Contraception
Depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of fractures; however, nothing is known about the risk associated with intrauterine contraceptive device (IUD) use. Case-control study. All women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was present or previous DMPA or IUD use (only IUD coated with hormones, not those coated solely with copper). Adjustments were made for confounders. DMPA use seemed to be associated with an increased risk of fractures [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.01-2.06], while IUD use appeared to be associated with a decreased risk of fractures (OR=0.75, 95% CI: 0.64-0.87). DMPA use may cause an increased risk of fracture. However, the fact that use of DMPA is rare in Danish women and the lack of baseline data including smoking status and BMI does not allow causal inferences to be made. Likewise, the seemingly decreased risk of fractures with IUD use is probably not a pharmacological effect but rather the effect of residual confounding related to nonincluded confounders regarding lifestyle.
Vestergaard P et al., 2008 Contraception
Little is known on fracture risk in young women using oral contraceptives. Case-control study (64,548 cases, 193,641 controls). Overall, no major association with risk of fracture was present. Only in a few age groups a limited increase (OR 1.1-1.5) was seen in those using low average doses (less than one tablet per day - i.e., intermittent use). Neither 20 nor >or=30 mcg per day of ethinylestradiol was associated with risk of fractures, while changing from 20 to >or=30 mcg per day or vice versa was associated with a limited increase in fracture risk (OR 1.1-1.4) in some age groups. In general, use of oral contraceptives in young women did not seem to be associated with an increased risk of fractures. The isolated increase seen in some strata with low average doses may be linked to factors associated with discontinuation of oral contraceptives rather than pharmacological effects.
McFarlane-Anderson N et al., 2008 BMC Womens Health Open Access
This study was conducted to determine whether use of hormonal contraceptives is associated with cervical dysplasia and cancer in a population where there is widespread use of hormonal contraception and the rates of cervical cancer remain high at 27.5/100,000. A case-control study was conducted among women visiting the colposcopy and gynaelogical clinics at a tertiary referral hospital. Two hundred and thirty six cases CIN I (72), II (59), III (54), cancer (51) and 102 controls, consented and were interviewed on use of contraceptives using a structured questionnaire. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of hormonal contraception in cases and controls and in low and high risk cases. Recruitment was carried out from 2001-2002. Contraceptives used were: oral contraceptives - 35%, injections (depot medroxy progesterone acetate (Depo-provera) - 10%, Intrauterine devices - 2%, combinations of these and tubal ligation - 30%. 23% reported use of 'other' methods, barrier contraceptives or no form of contraception. Barrier contraceptive use was not significantly different between cases and controls. Current and/or past exposure to hormonal contraceptives (HC) by use of the pill or injection, alone or in combination with other methods was significantly higher in the cases. In multivariate analysis with age and number of sexual partners as co-variates, use of hormonal contraception was associated both with disease, [OR, 1.92 (CI 1.11, 3.34; p = 0.02] and severity of the disease [OR, 2.22 (CI 1.05, 4.66) p = 0.036]. When parity and alcohol consumption were added to the model, hormonal contraception was no longer significant. The significant association with high risk disease was retained when the model was controlled for age and number of sexual partners. Depo-provera use (with age and number of sexual partners as covariates) was also associated with disease [OR, 2.43 (CI 1.39, 4.57), p = 0.006] and severity of disease [OR 2.51 (1.11, 5.64) p = 0.027]. With parity and alcohol added to this model, depo-provera use retained significance. Exposure to HC > 4 years conferred more risk for disease and severity of disease. Hormonal contraception did confer some risk of dysplasia and women using HC should therefore be encouraged to do regular Pap smear screening.
Vanakankovit N et al., 2008 J Med Assoc Thai
To assess the risk of oral contraceptives on the occurrence of cervical cancer. Material and A hospital-based case-control study was conducted. Sixty women patients with histologically confirmed invasive cervical cancer and 180 healthy women as the control group who attended the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were recruited. Information about the use of oral contraceptives and other cervical cancer risk factors were obtained from personal interviews. The risk factors were evaluated by using odds ratio (OR). 60 women with invasive cervical cancer and 180 healthy controls were interviewed by the investigators. Compared with non-users, patients who had ever used or currently used oral contraceptive had an increased risk of cervical cancer (OR 1.45; 95% CI 0.79-2.64). However the risk was not statistically significant. Considering the duration of use, patients who had used oral contraceptives for 3 years or less did not have an increased risk of cervical cancer (OR 0.78; 95% CI 0.39-1.77). Nevertheless, the odds ratio of oral contraceptive pill use for more than 3 years was 2.57 (95% CI 1.22-5.49) which was statistically significant. Long-term use of oral contraceptive might be a cofactor that increases the risk of cervical carcinoma. Further investigations should be conducted to confirm this risk. However, Pap smear has to be done routinely in long-term oral pill users.
International Collaboration of Epidemiological Studies of Cervical Cancer et al., 2007 Lancet
Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use. Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally. Relative risks of cervical cancer were estimated by conditional logistic regression, stratifying by study, age, number of sexual partners, age at first intercourse, parity, smoking, and screening. Findings: Among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]). The risk declined after use ceased, and by 10 or more years had returned to that of never users. A similar pattern of risk was seen both for invasive and in-situ cancer, and in women who tested positive for high-risk human papillomavirus. Relative risk did not vary substantially between women with different characteristics. Interpretation: The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases. 10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.
Trivers KF et al., 2007 Cancer Epidemiol Biomarkers Prev
Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Ageand income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years.
Sweeney C et al., 2007 Int J Cancer
Associations between oral contraceptive (OC) use and breast cancer have been reported, but few studies have considered associations in racial and ethnic minorities. Data regarding injected or implanted hormonal contraceptives are limited. In a case-control study of Hispanic (796 cases, 919 controls) and non-Hispanic white (1,522 cases, 1,596 controls) women in the U.S. southwest interviewed in 2000-2005, 49% of Hispanic controls and 66% of non-Hispanic white controls reported having used OC. Breast cancer odds ratios (OR) associated with OC use within the past 5 years were 1.22 (95% confidence interval (CI) 0.80, 1.84) among Hispanics, 1.28 (95% CI 0.93, 1.76) among non-Hispanic whites, 1.27 (95% CI 0.99, 1.63) for both ethnic groups combined and 1.53 (95% CI 0.98, 2.40) for estrogen receptor (ER) negative tumors. OC use for 20 years or longer was associated with ORs of 1.50 (95% CI 1.04, 2.17) for both ethnic groups combined, and 2.23 (95% CI 1.17, 4.25) for ER negative tumors. Hormonal contraceptive injections were used by 3.3% of Hispanic controls and 2.8% of non-Hispanic white controls, OR 1.23 (95% CI 0.88, 1.73). Fifteen cases and 2 controls reported use of a subdermal contraceptive implant, OR 8.59 (95% CI 1.92, 38.39). Associations between OC use and breast cancer in Hispanics are consistent with modestly increased risk among recent users and for ER negative tumors, as observed in other populations. Based on a small number of users of contraceptive implants, a significantly increased breast cancer risk was observed; continued surveillance of implant users may be warranted.
Mikolajczyk RT et al., 2007 Fertil Steril
To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration. We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC. Combined data from multiple clinical studies. PATIENT(S): Simulation models. INTERVENTION(S): Disruption of ovulation. MAIN OUTCOME MEASURE(S): Effectiveness in the form of proportion of pregnancies prevented. RESULT(S): With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay). CONCLUSION(S): The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.
Novikova N et al., 2007 Contraception
Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.
Folger SG et al., 2007 Cancer Causes Control
To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history. We analyzed data from the Women's Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35-64 years old, diagnosed with invasive breast cancer in July 1994-April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer. These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk.
Guven S et al., 2007 Medical hypotheses
Oral contraceptives (OCs) remain among the most effective reversible methods of birth control available today, providing almost 100% effectiveness with an impressively high margin of safety and other important health benefits. However, concerns have been raised about the role that the hormones in OCs might play in the pathogenesis of cervical cancer. Evidence shows that long-term use of OCs (five or more years) may be associated with an increased risk of cancer of the cervix. The mechanism of increased risk of cervical cancer in OCs users has long been debated, and remains uncertain. Our hypothesis is that scanty, thick, and highly viscous cervical mucus obtained in OCs users intimately involved in the pathogenesis of cervical cancer. Possibly, this architecture of cervical mucus may modulate and prolong the effect of carcinogenic agents, which have been carried by coitus and stored in posterior vaginal fornix, on squamocolumnar junction of cervix by not permitting them to be removed because of its highly viscous pattern. The role of cervical mucus changes by means of specific mucin protein changes on the pathophysiology of cervical cancer in OCs users should be investigated.
Kahlenborn C et al., 2006 Mayo Clin Proc
To perform a meta-analysis of case-control studies that addressed whether prior oral contraceptive (OC) use is associated with premenopausal breast cancer. We searched the MEDLINE and PubMed databases and bibliography reviews to identify case-control studies of OCs and premenopausal breast cancer published in or after 1980. Search terms used included breast neoplasms, oral contraceptives, contraceptive agents, and case-control studies. Studies reported in all languages were included. Thirty-four studies were identified that met inclusion criteria. Two reviewers extracted data from original research articles or additional data provided by study authors. We used the DerSimonian-Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the Mantel-Haenszel test to assess association between OC use and cancer. Use of OCs was associated with an increased risk of premenopausal breast cancer in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use. Among studies that provided data on nulliparous and parous women separately, OC use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20-1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85-1.96). Among parous women, the association was stronger when OCs were used before first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP (OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer risk was greatest for parous women who used OCs 4 or more years before FFTP (OR, 1.52; 95% CI, 1.26-1.82). Use of OCs is associated with an increased risk of premenopausal breast cancer, especially with use before FFTP in parous women.
Haile RW et al., 2006 Cancer Epidemiol Biomarkers Prev
Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice. We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years. For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later. We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue.
Vestergaard P et al., 2006 Contraception
Prior studies have suggested that oral contraceptives (OCs) may be associated with an increased fracture risk. However, the previous studies have only performed a limited adjustment for other potential risk factors. Subjects and methodsAll women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was use of OCs between January 1, 1996, and December 31, 2000. Adjustments were made for use of other drugs, pregnancy, prior fracture, other diseases and social variables. In the unadjusted analysis, use of OCs in low dose was associated with a small increase in overall fracture risk. However, upon adjustment, no increase in fracture risk could be demonstrated in any age or dose group. Oral contraceptives are not associated with an increase or a decrease in fracture risk. Any change in fracture risk may be due to confounders.
Curtis KM et al., 2006 Contraception Open Access
Questions have been raised about the effects of progestogen-only contraceptive use on bone health, particularly among young women who have not yet reached peak bone mass and perimenopausal women who may be starting to lose bone mass. We conducted a systematic review that evaluated the association between progestogen-only contraceptive use and fracture risk or bone mineral density (BMD). We identified 39 articles from MEDLINE and EMBASE, published through July 2005. One study reported that depot medroxyprogesterone acetate (DMPA) users were more likely to experience stress fractures than nonusers; this association was not statistically significant after controlling for baseline bone density. In cross-sectional studies, the mean BMD in DMPA users was usually below that of nonusers, but within 1 SD. In longitudinal studies, BMD generally decreased more over time among DMPA users than among nonusers, but women gained BMD upon discontinuation of DMPA. Limited evidence suggested that use of progestogen-only contraceptives other than DMPA did not affect BMD.
Silvera SA et al., 2005 Cancer Causes Control
Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrollment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73-1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (p(trend)=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47-1.19, p(trend)=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer.
Jernström H et al., 2005 Eur J Cancer
Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.
Barad D et al., 2005 Fertil Steril
To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause. A prospective cohort of 93,725 postmenopausal women. Forty Women's Health Initiative (WHI) clinical centers across the United States. PATIENT(S): Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire. RESULT(S): The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users. CONCLUSION(S): This study does not support the idea that past OC use protects against later fracture.
Milne RL et al., 2005 Cancer Epidemiol Biomarkers Prev
Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear. Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls. After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001). There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
Grimes DA et al., 2004 Cochrane Database Syst Rev
"Fertility awareness-based methods" (FAB) of family planning "involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature, or by monitoring cycle days. FAB methods can be used in combination with abstinence or barrier methods during the fertile time" (WHO 2000). Several names have been used to describe this approach to contraception, including "rhythm," "natural family planning" and "periodic abstinence." Fertility awareness-based methods can be used with abstinence from sexual intercourse. Alternatively, they can be used with barrier contraceptives or withdrawal during presumed fertile times. We retrieved and analyzed all randomized controlled trials that examined any fertility awareness-based methods used for contraception. We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its inception to January, 2004) for randomized controlled trials of fertility awareness-based methods. We examined the reference list of each trial as well as that of review articles. Selection Criteria: We included all randomized controlled trials in any language that compared any fertility awareness-based methods for contraception with a placebo; another method, including an alternative fertility awareness-based method; or fertility awareness-based methods used in conjunction with another contraceptive. We assessed all titles and abstracts found for inclusion. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design; randomization method; allocation concealment; blinding; premature discontinuation rates; and loss to follow-up rates. Because of methodological weaknesses, we could not enter the trial results in RevMan, calculate measures of association, or aggregate data. MAIN Because of poor methods and reporting, pregnancy rates could not be determined. A trial in Colombia found similar numbers of pregnancies among women randomized to the ovulation and symptothermal methods. In contrast, a companion trial in Los Angeles observed more pregnancies in the group assigned to the ovulation method. In the two U.S. trials, recruitment of participants was unexpectedly difficult; this aspect was not mentioned in the report from Colombia. Continuation rates were poor. In the two larger trials, most participants discontinued their assigned method before entering the observation phase of the trial. REVIEWERS' The comparative efficacy of fertility awareness-based methods of contraception remains unknown. Despite intensive training and ongoing support, most participants in these trials discontinued prematurely. Contraceptive methods should be properly evaluated, preferably in randomized controlled trials, before adoption and dissemination.
Stanford JB, 2004 The Medical and Surgical Practice of NaProTECHNOLOGY
Methodologically rigorous effectiveness data for the CrMS are presented, including method-effectiveness and use-effectiveness rates for pregnancy avoidance drawn from prospective cohort studies, demonstrating rates comparable to or exceeding hormonal contraception. Standardized outcome measurement is necessary to establish the CrMS's scientific credibility and to provide practitioners and patients with accurate, evidence-based counseling on system performance.
Mastorakos G et al., 2002 Fertil Steril
To compare the effects of cyproterone acetate and desogestrel, as part of combined oral contraceptives, on lipid metabolism and hirsutism of adolescents with polycystic ovary syndrome (PCOS). Prospective randomized clinical trial. Outpatient gynecology clinic (referral center) of a university. PATIENT(S): Twenty-eight adolescent girls with clinical and biological hyperandrogenism and six or less menses during the past 12 months. INTERVENTION(S): Group A (n = 14) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl estradiol daily. Group B (n = 14) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl estradiol daily. Treatment was given for 21 days followed by a 7-day rest for a period of 12 months. MAIN OUTCOME MEASURE(S): Hirsutism and lipid profile were evaluated before initiation and at 3, 6, 9, and 12 months of treatment. Androgen profile was evaluated before and at 12 months of treatment. RESULT(S): A significant decline of the Ferriman-Gallway hirsutism score was observed from the sixth month of therapy in both groups. During therapy, the levels of testosterone, free testosterone, Delta(4)-androstenedione, and 17OH-progesterone decreased significantly, whereas sex hormone-binding globulin (SHBG) increased significantly in both groups. The level of total cholesterol and low density lipoprotein (LDL) cholesterol increased significantly, whereas high density lipoprotein (HDL) cholesterol and apolipoprotein A-I increased significantly from the third month of therapy in both groups. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios remained unchanged. The levels of triglycerides increased significantly in the cyproterone acetate-treated group after the third month. CONCLUSION(S): Treatment of adolescent girls with PCOS with the two studied formulations is comparably effective in decreasing hirsutism and androgen levels. Both combined oral contraceptives are associated with an increase of total cholesterol, LDL cholesterol, and HDL cholesterol levels and no change of the total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios. Treatment with the cyproterone acetate combined oral contraceptive is associated with a tendency toward increasing the levels of triglycerides.
Moreno V et al., 2002 Lancet
Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA. We pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders. Findings: 1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use. Interpretation: Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.
Kahlenborn C et al., 2002 Ann Pharmacother
To assess the possibility of a postfertilization effect in regard to the most common types of hormonal emergency contraception (EC) used in the US and to explore the ethical impact of this possibility. DATA A MEDLINE search (1966-November 2001) was done to identify all pertinent English-language journal articles. A review of reference sections of the major review articles was performed to identify additional articles. Search terms included emergency contraception, postcoital contraception, postfertilization effect, Yuzpe regimen, levonorgestrel, mechanism of action, Plan B. The 2 most common types of hormonal EC used in the US are the Yuzpe regimen (high-dose ethinyl estradiol with high-dose levonorgestrel) and Plan B (high-dose levonorgestrel alone). Although both methods sometimes stop ovulation, they may also act by reducing the probability of implantation, due to their adverse effect on the endometrium (a postfertilization effect). The available evidence for a postfertilization effect is moderately strong, whether hormonal EC is used in the preovulatory, ovulatory, or postovulatory phase of the menstrual cycle. Based on the present theoretical and empirical evidence, both the Yuzpe regimen and Plan B likely act at times by causing a postfertilization effect, regardless of when in the menstrual cycle they are used. These findings have potential implications in such areas as informed consent, emergency department protocols, and conscience clauses.
d'Arcangues C et al., 2001 Contraception
Focus group research was conducted in four countries to understand how couples who use calendar methods determine when they are at risk of pregnancy, what behavior they adopt during the fertile phase, and whether or not they are satisfied with their method. Calendar and periodic abstinence method users do not all know how to make correct calendar calculations of the fertile period, report being sexually active during the fertile period, and desire a more comprehensive approach to sexual behavior during the fertile period. Men's roles in the methods should be enhanced, and credible resources in the community should be enlisted to improve education, information, and communication.
Prior JC et al., 2001 CMAJ
Positive and negative effects on bone mineral density (BMD) have been described as a result of the premenopausal use of oral contraceptives (OCs); increased fracture rates have also been reported. This study assessed the relation between OC use and BMD in a population-based, 9-centre, national sample of women aged 25-45 years. Premenopausal women who had been enrolled in the Canadian Multicentre Osteoporosis Study were classified as having ever been OC users (> or = 3 months) or as having never been OC users (0 to < 3 months). Data were obtained through extensive questionnaires and measuring of participants' weight, height and the BMD of lumbar vertebrae and the proximal femur. Of the sample of 524 women, whose mean age was 36.3 (standard deviation [SD] 5.9) years, 454 had used OCs; their mean age when they started using OCs was 19.8 (SD 3.5) years and the mean duration of use was 6.8 (SD 4.8) years. Women who had ever and those who had never used OCs showed no differences in age, age at menarche, parity, current calcium intake, exercise, body mass index (BMI), education, past irregular cycles or amenorrhea. OC users reported more alcohol and cigarette use and more use of medications to create regular cycles. Mean BMD values (adjusted for age, BMI and height) were 0.02-0.04 g/cm2 (that is, 2.3%-3.7%) lower in OC users, and were significantly lower in the spine and trochanter. The BMD of the spine in OC users was 1.03 (SD 0.12) g/cm2 versus 1.07 (SD 0.12) g/cm2 (95% confidence interval [CI] of difference -0.07 to -0.001) in those who had never used OCs. BMD was neither related to the duration of OC use nor to gynecological age at first use. Current and past users had similar BMD values. Interpretation: National, population-based data show lower BMD values for the trochanter and spine in premenopausal women who have used OCs compared with those who have never used OCs.
Larimore WL et al., 2000 Arch Fam Med
The primary mechanism of oral contraceptives is to inhibit ovulation, but this mechanism is not always operative. When breakthrough ovulation occurs, then secondary mechanisms operate to prevent clinically recognized pregnancy. These secondary mechanisms may occur either before or after fertilization. Postfertilization effects would be problematic for some patients, who may desire information about this possibility. This article evaluates the available evidence for the postfertilization effects of oral contraceptives and concludes that good evidence exists to support the hypothesis that the effectiveness of oral contraceptives depends to some degree on postfertilization effects. However, there are insufficient data to quantitate the relative contribution of postfertilization effects. Despite the lack of quantitative data, the principles of informed consent suggest that patients who may object to any postfertilization loss should be made aware of this information so that they can give fully informed consent for the use of oral contraceptives.
Hitchcock CL et al., 1999
Is Menstruation Obsolete? argues that regular monthly bleeding is not the “natural” state of women, and that it actually places them at risk of several medical conditions of varying severity. The authors maintain that while menstruation may be culturally significant, it is not medically meaningful. Moreover, they propose that suppressing menstruation has remarkable health advantages. Because of cultural changes, shorter durations of breast feeding, and birth control, the reproductive patterns of modern women no longer resemble that of their Stone age ancestors. Women have moved from the age of incessant reproduction to the age of incessant menstruation. Consequently, they often suffer from clinical disorders related to menstruation: anemia, endometriosis, and PMS, just to name a few. The authors encourage readers to recognize what has gone previously unnoticed that this monthly discomfort is simply not obligatory. They present compelling evidence that the suppression of menstruation is a viable option for women today, and that it can be easily attained through the use of birth control pills. In fact, they reveal that contraceptive manufacturers, knowing that many women equate menstruation with femininity and that without monthly bleeding would fear that they were pregnant, engineered pill dosage regimens to ensure the continuation of their cycles. Indeed, throughout history societies have assigned menstruation powerful meaning, and Is Menstruation Obsolete? presents a fascinating history of how menstruation inspired doctors to try therapeutic bleeding for a variety of ailments, and how this therapy remained dominant in Western medicine until the early 20th century. Is Menstruation Obsolete? offers women a fresh view of menstruation, providing them with the information they need to make progressive choices about their health. This is a message whose time has come.
Michaëlsson K et al., 1999 Lancet
Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. Findings: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. Interpretation: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.
Fehring RJ et al., 1998 Contraception
Small hand-held microscopes have been developed for self-observation of salivary ferning patterns to detect the fertile time of a woman's menstrual cycle. The purpose of this study was to evaluate one such microscope, the Lady Free Biotester, by comparing it with the self-observation of cervical-vaginal mucus and with the self-detection of luteinizing hormone (LH) in the urine. Twelve natural family planning teachers (average age 34.6 years) observed their cervical-vaginal mucus, tested their urine for LH, and observed salivary and cervical-vaginal mucus ferning patterns (with the Lady Free Biotester) for two menstrual cycles. Data indicated that there was a strong correlation between the LH in the urine and the peak in self-observed cervical-vaginal mucus ferning (r = 0.99, p < or = 0.001) and salivary ferning (r = 0.98, p < or = 0.001). However, it was difficult to assess the beginning and end of the fertile time based on the salivary ferning patterns. Further testing of salivary ferning patterns is recommended before widespread use of these devices for family planning.
Vessey M et al., 1998 Contraception
There is good evidence that estrogens and progestogens have an important effect on bone metabolism. This article explores the relationship between oral contraceptive (OC) use and fractures occurring at various sites among the 17,032 participants in the Oxford-Family Planning Association contraceptive study, which now includes information accumulated during 310,000 woman-years of observation between 1968 and 1994. In total, 1308 women suffered at least one fracture during the follow-up period, which was largely confined to premenopausal years. When all fractures were combined, there was a modest, but highly significant trend (p < 0.001) of increasing risk with total duration of oral contraceptive use. In addition, there was statistically significant heterogeneity (p < 0.01) when overall fracture rates were examined in relation to recency of oral contraceptive use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1-1.5) was for current or recent oral contraceptive users; however, viewed as a whole, no clear pattern of risk was apparent. Examination of the data for individual fracture sites (including the lower end of the radius/ulna) did not provide any evidence of a protective effect of oral contraceptive use. These results are closely similar to those reported from the Royal College of General Practitioners Oral Contraception Study in 1993. Estrogens and progestogens have an important effect on bone metabolism. The present study explored the relationship between oral contraceptive (OC) use and bone fractures in the cohort of 17,032 English and Scottish participants in the Oxford-Family Planning Association contraceptive study (1968-94). The analysis was based on the calculation of woman-years of observation terminated by referral for fracture or release from follow-up due to death, emigration, or short-term pill users reaching age 45 years. A total of 1308 women experienced at least one fracture during 310,000 woman-years of observation and there was a significant (p 0.001) positive relationship between age and fracture risk. Most common were fractures of the radius/ulna, tarsal/metatarsal bones, and ankle. When all fractures were combined, there was a significant (p 0.001) increasing risk with total duration of OC use. Also observed was a significant (p 0.01) heterogeneity when overall fracture rates were examined in relation to recency of OC use during the premenopausal lifespan. The highest relative risk (1.3; 95% confidence interval, 1.1-1.5) was recorded among current or recent OC users. There was about a 20% increase in the overall risk of fracture in women who had used OCs at any time compared with never-users. Overall, however, no clear pattern of risk emerged. These results are similar to those reported in the 1993 Royal College of General Practitioners OC Study. It is assumed that the increased fracture risk in OC users results from life-style characteristics of such women rather than a direct effect of OCs on bone.
Fehring RJ, 1996 J Am Acad Nurse Pract
The purpose of this study was to compare the CUE Ovulation Predictor with the ovulation method in determining the fertile period. Eleven regularly ovulating women measured their salivary and vaginal electrical resistance (ER) with the CUE, observed their cervical-vaginal mucus, and measured their urine for a luteinizing hormone (LH) surge on a daily basis. Data from 21 menstrual cycles showed no statistical difference (T = 0.33, p = 0.63) between the CUE fertile period, which ranged from 5 to 10 days (mean = 6.7 days, SD = 1.6), and the fertile period of the ovulation method, which ranged from 4 to 9 days (mean = 6.5 days, SD = 2.0). The CUE has potential as an adjunctive device in the learning and use of natural family planning methods.
Raman-Wilms L et al., 1995 Obstet Gynecol
To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes. One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94). There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.
Kambic RT et al., 1994 Adv Contracept
This paper describes the evaluation of a new method of natural family planning (NFP) in Liberia. The Modified Mucus Method (MMM) was developed to address the need for a simple method of charting for poor and illiterate women. The acceptance, use, and cost-effectiveness of the MMM were compared with standard NFP methods, the sympto-thermal and ovulation method (ST/OM), used in the same population. The personal discontinuation rate of MMM users was 27.3 per 100 women per year compared with 3.2 among ST/OM users. Unplanned pregnancy rates were low for both MMM and ST/OM, 6.6 and 1.5 respectively. The cost per couple year protection (CYP) for MMM was $55.80 and for ST/OM $56.10. There were differences in characteristics between MMM and ST/OM clients. The MMM clients were more likely to have attended school and to have used a family planning method previously, and were less likely to be housewives. We conclude that the MMM in Liberia was provided to an inappropriate sample of women, educated and middle-class rather than poor and illiterate. The MMM users were dissatisfied and discontinued at the rate of 44 per 100 women entering per year. This is an unfair evaluation of the MMM because of the unsuitable study population. It is our opinion that the MMM needs more study to become part of the inventory of birth spacing methods.
No Authors Listed, 1993 Adv Contracept
Since 1989 an international multicenter prospective study to evaluate the effectiveness and acceptability of natural family planning (NFP) methods in Europe has been conducted by the NFP Research Center at the University of Düsseldorf in collaboration with the European Zone of the International Federation for Family Life Promotion (IFFLP). Fourteen NFP-organizations from nine European countries participate in the study. Cycle data from women in the fertile age group are transferred to a special standard computer sheet by the respective organizations and forwarded at three-monthly intervals to the study center for analyses. To date, 10,045 cycles from 900 women aged between 19 and 54 years have been analyzed. This paper presents the pregnancy rate for the women aged between 19 and 45 years of age, who contributed 9284 cycles. In the analyses the cycles were subdivided into two categories consequent to sexual practices during the fertile phase: group I (NFP only--4277 cycles) use only NFP to avoid a pregnancy; group II (FA/mix--5007 cycles) where barrier methods or coitus interruptus during the fertile phase, at least in some cycles, were used to avoid a pregnancy. The women used different clinical indicators such as basal body temperature (BBT), cervical mucus, calculations, cyclical cervical changes or combinations of these to determine the beginning and the end of the fertile phase necessitating a further division into four subgroups, A, B, C, D, and different efficiency rates for each of these groups. In group A (symptothermal method, double check) 15 unintended pregnancies (UIP) occurred in 7404 cycles, giving a pregnancy rate of 2.4 Pearl Index (PI); in group B (muco-thermal method) there were 12 UIP in 1352 cycles with a pregnancy rate of 10.6 (PI); in group C (mucus to detect the beginning and mucus and BBT to determine the end of the fertile phase) there was one UIP in 434 cycles, and in group D (mucus method only) there was one IUP in 70 cycles. The numbers in group C and D are too small to calculate a pregnancy rate (PI). No pregnancy was observed in women over 40 years of age. Our conclusion from these preliminary results is that in the continent of Europe, the symptothermal method when used with periodic abstinence (NFP only = group I) and fertility awareness with the use of barriers during the fertile phase (FA/mix = group II) are effective methods of family planning.(ABSTRACT TRUNCATED AT 400 WORDS)
Gray RH et al., 1993 J Biosoc Sci
Studies to evaluate use-effectiveness and cost-effectiveness of natural family planning (NFP) were conducted in Liberia and Zambia. The Liberian programme provided uni-purpose NFP services to 1055 clients mainly in rural areas; the Zambian programme provided NFP services integrated with MCH to 2709 clients predominantly in urban areas. The one-year life table continuation and unplanned pregnancy rates were 78.9 and 4.3 per 100 woman-years in Liberia, compared to 71.2 and 8.9 in Zambia. However, high rates of loss to follow-up mandate caution in interpretation of these results, especially in Zambia. More women progressed to autonomous NFP use in Liberia (58%) than in Zambia (35.3%). However, programme costs per couple-year protection were lower in Zambia (US$25.7) than in Liberia (US$47.1). Costs per couple-year protection were higher during learning than autonomy, and declined over time. These studies suggest that NFP programmes can achieve acceptable useand cost-effectiveness in Africa.
Cooper C et al., 1993 Bone
It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08-1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life.
Neely JL et al., 1991 Obstet Gynecol
Doxycycline and other antibiotics have been implicated in oral contraceptive (OC) failure, but information is sparse and studies of a doxycycline-OC interaction are nonexistent. Because an interaction between doxycycline and OCs, especially those containing low-dose estrogen, could result in an unplanned and unwanted pregnancy, a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed. Twenty-four women aged 18-35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic. While they were on a steady dose of the OC Ortho-Novum 1/35, serum concentrations of ethinyl estradiol, norethindrone, and endogenous progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control phase). These measurements were repeated on days 18, 19, and 20 of the following menstrual cycle while the patient was taking doxycycline, 100 mg twice daily (treatment phase). No statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone were seen between the control and treatment phases. However, there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels. No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase. It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation. Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at risk.
1991 CCL family foundations
Users of natural family planning (NFP) methods of birth control should be aware of the medications that can effect their ability to read their fertility signs. Antihistamines and decongestants are the most common medications that can affect the mucus signs. Antihistamines tend to dry up the mucus while decongestants tend to liquify mucus. Some anti-depressants sometime act like antihistamines while steroids like cortisone do not change the signs but can lengthen the cycle. Although with cortisone it seems to depend on when in the cycle it is administered. Finally, while antibiotics do not effect the cycle they can cause a secondary yeast infection. These yeast infections can in turn make reading difficult. The solution is to eat yogurt, take lactobacillus tablets or drink acidophilus milk before, during and after taking antibiotics.
Klaus H et al., 1988 Stud Fam Plann
Five programs of instruction in the ovulation method (OM) in diverse geographic and cultural settings are described, and characteristics of approximately 200 consecutive OM acceptors in each program are examined. Major findings include: the religious background and family size of acceptors are variable, as is the level of previous contraceptive use. Acceptors are drawn from a wide range of socioeconomic and religious backgrounds; however, family planning intention was similarly distributed in all five countries. In sum, the ovulation method is accepted by persons from a variety of backgrounds within and between cultural setting.
Vessey M et al., 1986 Br Med J (Clin Res Ed) Open Access
Since the start in 1968 of the Oxford Family Planning Association contraceptive study 31 women have developed ulcerative colitis and 18 have developed Crohn's disease, giving incidences of 0.15 and 0.09/1000 woman years respectively. The incidence of ulcerative colitis in women who were non-smokers on entry to the study was 0.17/1000 woman years and the incidence in smokers was 0.11/1000 woman years. The findings for Crohn's disease were entirely different, the corresponding incidences being 0.05 and 0.17/1000 woman years respectively. Both ulcerative colitis and Crohn's disease were more common among women currently using oral contraceptives than among those not doing so. Incidences per 1000 woman years for ulcerative colitis were 0.26 in users and 0.11 in non-users; for Crohn's disease the incidences were 0.13 and 0.07 respectively. Though the association between the use of oral contraceptives and chronic inflammatory bowel disease cannot be regarded as established, the effects of smoking have been shown consistently in many studies. This observation provides an important clue to the aetiology of chronic inflammatory bowel disease.
Fotherby K et al., 1986 Journal of obstetrics and gynaecology
2 recent studies largely dispel concern about the restoration of fertility after discontinuation of injectable contraceptives. After cessation of use of depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate there is some delay in fertility restoration, but fertility is not impaired once the progestogen is cleared from the body. Pharmacokinetic data suggest that norethisterone enanthate exerts less of an inhibitory effect on the hypothalamic-pituitary-ovarian system than DMPA, so that ovulation returns earlier after discontinuation of the former injectable. There appears to be no significant difference between nulligravid and parous women in the return of fertility, indicating that use of injectable contraceptives does not need to be restricted to women who have completed their families. In Pardthaisong's study of over 1000 Thai women, the median delay until conception after contraceptive discontinuation was 3 months among oral contraceptive users, 4.5 months for the IUD, and 5.5 months for DMPA users. 36 months after discontinuation, only 6.4% of the 796 DMPA former users surveyed had failed to conceive. In a smaller scale study by Fotherby et al, the conception rate among discontinuers of norethisterone enanthate did not differ significantly from that among nonusers of contraception or users of nonsteroidal methods once an 8-week period for the clearance of norethisterone from the body had elapsed. The mean time to ovulation is similar to the clearance for norethisterone; for DMPA, in contrast, the mean time to ovulation is considerably longer than that of the clearance. In discontinuers of DMPA, the mean time for the return of ovulation (210 days) is only slightly less than the mean time for the return of fertility (260 days). However, for norethisterone enanthate, the mean time to conception is about 170 days compared to just over 80 days for the return of ovulation.
Hatherley LI, 1985 Clin Reprod Fertil
The use-effectiveness of natural methods of family planning in lactation is evaluated by comparing the incidence of unplanned pregnancies in a group of nursing mothers practising these methods with the incidences reported previously in surveys of breastfeeding women using no contraception. The complexity of the physiological processes involved in the resumption of ovulation after term pregnancy is discussed in relation to NFP and the problems encountered by its users in the context of normal family life. The serum prolactin and gonadotrophin levels are correlated with the postpartum interval and nursing status of the participants and discussed in relation to NFP after childbirth.
Tarara R, 1984 Teratology
Six female olive baboons (Papio cynocephalus anubis) were treated with a single dose of 150 mg of Depo-Provera i.m. at day 30 of pregnancy, approximately three times the human dose equivalent on a body weight basis. Fetectomies were performed at day 100 of gestation. The body weights and measurements of the five live fetuses were comparable to age-matched controls and no gross or histologic abnormalities were seen. The dead fetus was in an advanced state of decomposition. This preliminary study suggests that, at levels up to three times that used for human contraception, Depo-Provera does not appear to have any adverse effects on fetal development.
No Authors Listed, 1982 Res Reprod
Pip: The concept of utilizing changes in cervical secretion offers a potentially simple method of natural family planning. A detailed international trial has been conducted to test the effectiveness of the method. 5 centers are involved: Auckland; Bangalore; Dublin; Manila; and San Miguel. The observations provide an indication of the value and success of the method. They also reveal interesting variations between the different centers and between various socioeconomic classes. The work was divided into a teaching phase and an effectiveness phase. The initial phase was designed to teach individual women how to recognize the symptoms in cervical mucus, and it usually covered the first 3 complete cycles. The subjects were ovulatory, of proven fertility, less than 39 years, nonlactating, and with a history of a menstrual cycle of between 23 and 35 days. Data were collected from the patient and returned to the organizers for analysis. Comparisons were then made between different centers on the 2 study phases. In the teaching phase 94% of the women could soon recognize and record their own cervical mucus symptoms. Many women could understand the principle of the method within the 1st teaching cycle. Almost 90% of the subjects completed the teaching phase, and 7% discontinued for various reasons, including 1.3% who failed to learn the method, and 5% who became pregnant. The average number of days of abstinence by the method was 17 in the 3rd teaching cycle, a high proportion of the length of the average menstrual cycle. After the teaching phase, 725 subjects were studied in an effectiveness phase which lasted for 13 cycles. More than 7500 cycles were analysed. High rates of method failures were found in the 2 most socially developed centers, Auckland and Dublin. Pearl rates for method failure ranged from 9.4/100 women years in Auckland to 1.1 in Manila and 0 in Bangalore and San Miguel. The accumulative probability of discontinuation after 13 cycles was 35.6%, more than half of this figure being due to pregnancy. Detailed pregnancy rates/100 woman years, using the modified Pearl Index, were found to be as follows: conscious departure from the rules of the method, 15.4; inaccurate application of instructions 3.5; method failure 2.8; inadequate teaching 0.4; and uncertain reasons 0.5. Subjects were not selected randomly.
Billings JJ, 1982 Am J Obstet Gynecol
Wade et al.'s report, entitled "A randomized prospective study of the use-effectiveness of 2 methods of natural family planning," contains items worthy of emphasis. These includes the following: 1) less than 5% of the women in the study were prevented from using the method assigned them because of problems in identifying their cervical mucus pattern; 2) those who were unable or unwilling to adhere to the methodology were encouraged to drop out; 3) the largest single category of pregnancies occurred in both groups when the volunteers failed to follow the rules for avoiding pregnancy; 4) it was judged that there were 6 pregnancies in the ovulation method group to be classified as method failures, apparently for a total of 4501 cycles, which gives a method-failure rate of 1.6%; 5) couples were required to sign an informed consent statement of their awareness that the chances of the occurrence of pregnancy could be as high as 25% for the ovulation method; 6) recruiting difficulties constituted an important finding, primarily because they were unexpected by the investigators; 7) the volunteers recruited into the trial were restricted to those women whose menstrual cycles were 24-36 days; 8) the couples who failed to continue with the use of these 2 natural methods--ovulation and temperature rhythm--were on the average younger, more sexually active, and had fewer children; and 9) the ovulation method brings the partners into confrontation with their fertility in each cycle, and this has marked psychological results, including an awakening of the suppressed desire for that fertility to become creative of human life.
Lönnerdal B et al., 1980 The American journal of clinical nutrition
Nitrogen and protein composition was determined in milk from women using oral contraceptives during lactation. Total nitrogen and nonprotein nitrogen as well as lactose and the individual milk proteins lactoferrin, alpha-lactalbumin, and serum albumin were analyzed before introduction of oral contraceptives and thereafter throughout the lactation period. Twenty-four hour milk volumes were registered by weighing the infant before and after each feeding. The four oral contraceptives used consisted of different combinations of d-norgestrel, megestrolacetate, and ethinylestradiol. Significant changes were observed between groups and controls for all parameters studied. However, the changes observed were generally within the physiological variation of normal breast milk. It is suggested that the use of oral contraceptives during lactation should be limited.
Hilgers TW, 1980 Am J Obstet Gynecol
I read with interest the recent article by Wade and associates, "A randomized prospective study of the use-effectiveness of 2 methods of natural family planning: an interim report" (134: 628, 1979). In reference to the study of the ovulation method, the authors noted that abstinence begins on the 1st day of mucus secretion and continues until the evening of the 4th day beyond the peak or maximal mucus secretion. In the ovulation method, the peak symptom is not the same as maximal mucus secretion as was indicated in the paper. The peak symptom is defined as the last day of the mucus discharge that is clear and/or stretchy and/or lubricative. In the definition of peak symptom, the amount of mucus discharge is not specifically important and may often be misleading. I had the opportunity to do a site visit at this study at the request of the National Institutes of Health while the study was in progress. I analyzed several pregnancies which occurred in users of this ovulation method. Some of the pregnancies occurred as the result of poor teaching of the concept of peak symptom. In the ovulation method, proper understanding and teaching of that concept are essential to the measurement of its effectiveness. Noticeably missing from this interim report was any discussion of the quality control procedures which were utilized to guarantee a high-quality educational service to the people entered into the study. While the authors claim that the methods were taught by professional teachers, these teachers were actually women who had previously used the method and/or had formalized training in teaching the method. Simple use of either of the methods certainly does not qualify an individual to teach natural family planning. For those with formalized teaching, such training should have been outlined since judgment on the effectiveness of the teaching cannot be made; such a judgment is essential to the proper analysis of results. Finally, while the study claims to be a use-effectiveness study, it is rather a modified version of extended use-effectiveness. No objective definition of "user failure" is provided. One cannot ascertain how many pregnancies were related to poor teaching, nor can one tell how many occurred as the result of the couples' last minute exercise of their freedom to use their fertility. The use-effectiveness of the 2 methods under study as a means to achieve a pregnancy have been ignored. In doing so, the investigators have ignored use-effectiveness reality.
Evrard JR et al., 1976 American Journal of Obstetrics and Gynecology
A prospective study was done on 326 nulliparous women who ceased oral contraception. Follow-up was obtained on 311. The mean age was 20.3 years (SD 2.5). Eighty-nine per cent began menstruating within 60 days after stopping therapy, and only 7 took 180 days or longer to menstruate. Late menarche strongly correlated with post-pill amenorrhea (PPA), but continuous length of time on oral contraceptives and type of oral contraceptive showed no significant relationship. The incidence of PPA was 2.2 per cent. All women did eventually menstruate spontaneously, the longest period of amenorrhea being 540 days. The less the number of years between menarche and the beginning of oral contraceptives, the longer it took these patients to menstruate.
Lewit S et al., 1968 Demography
The recent advent of national family planning programs and the expansion of local programs have created an acute need for accurate statistical evaluation of contraceptive methods. Effectiveness in terms of pregnancy rates and continuation or discontinuation of use of the contraceptive method or methods under study have emerged as the major criteria in such evaluations.