Gallo, M. F., Lopez, L. M., Grimes, D. A., Carayon, F., Schulz, K. F., & Helmerhorst, F. M. (2014). Combination contraceptives: effects on weight. The Cochrane database of systematic reviews, 2014(1), CD003987. https://doi.org/10.1002/14651858.CD003987.pub5
Gallo, M. F., et al. "Combination contraceptives: effects on weight." The Cochrane database of systematic reviews, vol. 2014, no. 1, 2014, pp. CD003987.
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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.
Objectives
The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight.
Search Methods
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initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search.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 Results
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' Conclusions
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.
Lopez LM et al., 2016·Cochrane Database Syst Rev·Free full text on PubMed Central
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.
Lopez LM et al., 2015·Cochrane Database Syst Rev·Free full text on PubMed Central
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.
Grimes DA et al., 2014·The Cochrane database of systematic reviews·Free full text on PubMed Central
Functional ovarian cysts are a common gynecological problem among women of reproductive age worldwide. When large, persistent, or painful, these cysts may require operations, sometimes resulting in removal of the ovary. Since early oral contraceptives were associated with a reduced incidence of functional ovarian cysts, many clinicians inferred that birth control pills could be used to treat cysts as well. This became a common clinical practice in the early 1970s. This review examined all randomized controlled trials that studied oral contraceptives as therapy for functional ovarian cysts. In March 2014, we searched the databases of CENTRAL, PubMed, EMBASE, and POPLINE, as well as clinical trials databases (ClinicalTrials.gov and ICTRP). We also examined the reference lists of articles. For the initial review, we wrote to authors of identified trials to seek articles we had missed. We included randomized controlled trials in any language that included oral contraceptives used for treatment and not prevention of functional ovarian cysts. Criteria for diagnosis of cysts were those used by authors of trials. Two authors independently abstracted data from the articles. One entered the data into RevMan and a second verified accuracy of data entry. For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio with 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference with 95% CI. We identified eight randomized controlled trials from four countries; the studies included a total of 686 women. Treatment with combined oral contraceptives did not hasten resolution of functional ovarian cysts in any trial. This held true for cysts that occurred spontaneously as well as those that developed after ovulation induction. Most cysts resolved without treatment within a few cycles; persistent cysts tended to be pathological (e.g., endometrioma or para-ovarian cyst) and not physiological. AUTHORS' Although widely used for treating functional ovarian cysts, combined oral contraceptives appear to be of no benefit. Watchful waiting for two or three cycles is appropriate. Should cysts persist, surgical management is often indicated.
van Hylckama Vlieg A et al., 2009·BMJ·Free full text on PubMed Central
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.
Ibrahim H et al., 2019·Journal of Taibah University Medical Sciences·Free full text on PubMed Central
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.
Vickery Z et al., 2013·Contraception·Free full text on PubMed Central
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.
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.
Mosorin ME et al., 2023·Acta Obstet Gynecol Scand·Free full text on PubMed Central
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.
Maria F Gallo, David A Grimes, Kenneth F Schulz, Florence Carayon, Frans M Helmerhorst, Laureen M Lopez
M Gallo, Dave Grimes, D Grimes, Ken Schulz, K Schulz, F Carayon, F Helmerhorst, L Lopez
PMID 24477630 24477630 DOI 10.1002/14651858.CD003987.pub5 10.1002/14651858.CD003987.pub5 Gallo et al. 2014, Gallo 2014
Cite this article
Gallo, M. F., Lopez, L. M., Grimes, D. A., Carayon, F., Schulz, K. F., & Helmerhorst, F. M. (2014). Combination contraceptives: effects on weight. The Cochrane database of systematic reviews, 2014(1), CD003987. https://doi.org/10.1002/14651858.CD003987.pub5
Gallo, M. F., et al. "Combination contraceptives: effects on weight." The Cochrane database of systematic reviews, vol. 2014, no. 1, 2014, pp. CD003987.
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