Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder.
Methods
We searched medical and scientific databases, approached pharmaceutical companies, and reviewed citations of relevant articles to identify 29 studies of the use of SSRIs in PMS. 14 were excluded (no placebo group, preliminary report of included trial, or low quality). 15 randomised placebo-controlled trials were included. Information on study design, participants, drugs used and dosing regimens, outcome measures, side-effects, and sources of funding was extracted. Standardised mean differences between treatment and placebo groups were calculated to obtain an overall estimate of efficacy. The primary outcome measure was a reduction in overall PMS symptoms.
Findings
The primary analysis included data on 904 women (570 assigned active treatment and 435 assigned placebo, including 101 in crossover trials). The overall standardised mean difference was -1.066 (95% CI -1.381 to -0.750), which corresponds to an odds ratio of 6.91 (3.90 to 12.2) in favour of SSRIs. SSRIs were effective in treating physical and behavioural symptoms. There was no significant difference in symptom reduction between continuous and intermittent dosing or between trials funded by pharmaceutical companies and those independently funded. Withdrawal due to side-effects was 2.5 times more likely in the active-treatment group than in the placebo group.
Interpretation
SSRIs are an effective first-line therapy for severe PMS. The safety of these drugs has been demonstrated in trials of affective disorder, and the side-effects at low doses are generally acceptable.
PMID 11030291 11030291 DOI 10.1016/s0140-6736(00)02754-9 10.1016/s0140-6736(00)02754-9
Cite this article
Dimmock, P. W., Wyatt, K. M., Jones, P. W., & O'Brien, P. M. (2000). Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. Lancet (London, England), 356(9236), 1131-1136. https://doi.org/10.1016/s0140-6736(00)02754-9
Dimmock PW, Wyatt KM, Jones PW, O'Brien PM. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. Lancet. 2000;356(9236):1131-1136. doi:10.1016/s0140-6736(00)02754-9
Dimmock, Paul W., et al. "Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review." Lancet (London, England), vol. 356, no. 9236, 2000, pp. 1131-1136.
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. Literature search conducted in databases from January 1990 till August 2019 using various search terms. 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. 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.
Contraception/ComparisonBreast Cancer RiskLong-Term Side EffectsMeta-Analysis
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). 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 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.
To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.