Abstract

Objective: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).

Design: A systematic review and meta-analysis was performed, Prospero CRD42022345640.

Methods: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.

Results: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.

Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m² [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.

Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33–0.43}]) and BMI (MD 0.62 kg/m² [95% CI 0.05–1.20]) compared with conventional COCPs.

There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.

Conclusion: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.

Trial registration: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.