Combined Oral Contraceptives to Treat Depression in PMS, PMDD


Combined oral contraceptives were found to be moderately more efficacious than placebo for treating overall premenstrual symptomatology in women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).

Combined oral contraceptives were found to be moderately more efficacious than placebo for treating overall premenstrual symptomatologyin women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD), according to a meta-analysis of 9 randomized clinical trials in the American Journal of Obstetrics & Gynecology.1

However, the review concluded that combined oral contraceptives were not effective for treating premenstrual depressive symptoms specifically.

“Oral contraceptives are often considered a treatment option for women with PMS or PMDD, but evidence remains scarce,” said senior author Anouk de Wit, MD, PhD, a clinical epidemiologist at University Medical Center Groningen in the Netherlands. “Therefore we wanted to summarize the existing evidence so clinicians and patients can make well-informed choices about the therapeutic options.”

The authors searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, PsycINFO, EMCare, and Embase databases from inception to June 2021.

The 9 eligible studies comprised a total of 1,205 women with either PMS or PMDD. The mean patient age per study ranged from 24.6 to 36.5 years.

The studies examined 9different interventions—8distinct combined oral contraceptives and 1 placebo.

All studies assessed the effect of the premenstrual intervention,administered in the final week before the onset of menses,after 3 months of treatment.

Overall, 4 of the trials were rated as high risk of bias, while the remaining 5 were rated as moderate risk.

None of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology.

“Our results challenge the presumed efficacy of oral contraceptives in treating depressive symptoms, which is one of the core complaints of women with PMDD,” de Wit told Contemporary OB/GYN®. “Based on these results, women and clinicians can consider oral contraceptives as a treatment for overall premenstrual symptomatology; however, the depressive symptoms will likely not resolve. Hence, other treatment options for such symptoms should be considered.”

For women with PMDD who mostly report depressive symptoms, other popular treatment options might be a more effective approach, such as selective serotonin reuptake inhibitors or cognitive behavioral therapy. “But the certainty of evidence for any available treatment is very low to moderate at best,” de Wit said.

Also, because there is no evidence for 1oral contraceptive being more efficacious than another, “the choice for a specific oral contraceptive should be based on the preferences of the patient and her doctor,” added de Wit.

Contrary to popular belief, the review found no evidence of difference in efficacy among formulations containing drospirenone and other formulations or a 24-day regimen versus other regimens.

“Nonetheless, because drospirenone is linked to an increased risk of blood clots compared to other hormonal contraceptives,preferentially prescribing a drospirenone-containing contraceptive may not be in the patient’s best interest,” de Witt said.

Additionalrandomized clinical trials with head-to-head comparisons of combined oral contraceptives are required to determine which formulation is most effective for premenstrual complaints among women with PMS or PMDD, de Witt concluded.

This article originally appeared on Contemporary Ob/Gyn.


  1. de Wit AE, de Vries YA, de Boer MK, et al. Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in premenstrual syndrome: pairwise and network meta-analysis of randomized trials. Am J Obstet Gynecol. 2021 Dec;225(6):624-633. doi:10.1016/j.ajog.2021.06.090
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