Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in premenstrual syndrome: pairwise and network meta-analysis of randomized trials.

OBJECTIVE: Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome or premenstrual dysphoric disorder also seeking contraception, but evidence for this treatment is scarce. We aimed to determine (1) the level of evidence for the efficacy of combined oral contraceptives in managing premenstrual depressive symptoms and overall premenstrual symptomatology and (2) the comparative efficacy of combined oral contraceptives (the International Prospective Register of Systematic Reviews registration number CRD42020205510). DATA SOURCES: We searched Cochrane Central Register of Controlled Trials, PubMed, Web of Science, PsycINFO, EMCare, and Embase from inception to June 3, 2021. STUDY ELIGIBILITY CRITERIA: All randomized clinical trials that evaluated the efficacy of combined oral contraceptives in women with premenstrual syndrome or premenstrual dysphoric disorder were considered eligible for inclusion in this meta-analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A random effect Bayesian pairwise and network meta-analysis was conducted with change in premenstrual depressive symptoms and overall premenstrual symptomatology between baseline and 3 cycles as outcome. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Of 3664 records, 9 eligible trials were included that studied 1205 women with premenstrual syndrome or premenstrual dysphoric disorder (mean age per study range, 24.6-36.5 years). The pairwise meta-analysis revealed that combined oral contraceptives were more efficacious than placebo in treating overall premenstrual symptomatology (standardized mean difference, 0.41; 95% credible interval, 0.17-0.67), but not premenstrual depressive symptoms specifically (standardized mean difference, 0.22; 95% credible interval, -0.06 to 0.47). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology. CONCLUSION: Combined oral contraceptives may improve overall premenstrual symptomatology in women with premenstrual syndrome or premenstrual dysphoric disorder, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other.

Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials.

BACKGROUND: Observational studies suggest that hormonal contraceptive use may increase depressive symptoms in women, but it is unclear whether the effect is causal. AIMS: To quantitatively examine the evidence from randomised clinical trials for the link between hormonal contraceptive use and depressive symptoms. METHOD: We performed a systematic review and network meta-analysis of randomised clinical trials comparing women randomised to any form of a hormonal contraceptive with women randomised to any other form of a (non-)hormonal contraceptive or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, EMCare and EMBASE, from inception to 1 May 2020. Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A random-effect Bayesian network meta-analysis was conducted, with change in depressive symptoms between baseline and three cycles as outcome. RESULTS: This review identified 3492 records, of which 14 trials were eligible and 12 could be included in the network meta-analysis. These trials included 5833 participants (mean age per study range: 16.8-32.4 years) and compared 10 different interventions. Compared with placebo, hormonal contraceptive use did not cause worsening of depressive symptoms (standardised mean difference: median, -0.04; range, -0.17 [95% credible interval -0.46 to 0.13] to 0.13 [95% credible interval -0.28 to 0.56]). CONCLUSIONS: This study suggests that hormonal contraceptive use does not lead to an increase in depressive symptoms in adult women. Future studies should include first-time users, to confirm the results in young women.