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 (PMS) or premenstrual dysphoric disorder (PMDD) 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 (PROSPERO registration number CRD42020205510).

DATA SOURCES: We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, Emcare, and EMBASE from inception to June 3rd, 2021.

STUDY ELIGIBILITY: All randomized clinical trials that evaluated efficacy of combined oral contraceptives in women with PMS or PMDD were considered eligible for inclusion in the present 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, nine eligible trials were included that studied 1205 women with PMS or PMDD (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 SMD [95%CrI], 0.41 [0.17, 0.67]), but not premenstrual depressive symptoms specifically (SMD [95%CrI], 0.22 [-0.06, 0.47]). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology.

CONCLUSIONS: Combined oral contraceptives may improve overall premenstrual symptomatology in women with PMS or PMDD, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other.