Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 37554096 · doi:10.1210/clinem/dgad465
What was done
A systematic review and meta-analysis was conducted for the 2023 International PCOS Guidelines update, searching Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL. The authors evaluated randomized controlled trials in women with polycystic ovary syndrome comparing combined oral contraceptive pills, metformin, and combination treatment. Anthropometric, metabolic, and hyperandrogenic outcomes were analyzed using mean differences and 95% confidence intervals, with quality assessed via GRADE.
What was found
The search identified 1660 publications and included 36 randomized controlled trials. For hirsutism, no differences were found between metformin and combined oral contraceptive pills, nor between combined oral contraceptive pills and combination treatment. Compared with combined oral contraceptive pills, metformin was inferior for free androgen index (mean difference 7.08, 95% CI 4.81 to 9.36), sex hormone binding globulin (-118.61 nmol/L, 95% CI -174.46 to -62.75), and testosterone (0.48 nmol/L, 95% CI 0.32 to 0.64). Metformin lowered insulin (-27.12 pmol/L, 95% CI -40.65 to -13.59) and triglycerides (-0.15 mmol/L, 95% CI -0.29 to -0.01) compared with combined oral contraceptive pills. Compared with combination treatment, combined oral contraceptive pills were inferior for free androgen index (0.58, 95% CI 0.36 to 0.80), sex hormone binding globulin (-16.61 nmol/L, 95% CI -28.51 to -4.71), insulin (17.03 pmol/L, 95% CI 7.79 to 26.26), and insulin resistance (0.44, 95% CI 0.17 to 0.70), while testosterone did not differ.
Why it matters
This review clarifies that combined oral contraceptive pills preferentially improve biochemical androgen markers while metformin targets metabolic disturbances, with combination therapy providing additive benefits across both domains.
Limits
Total participant count, trial durations, specific contraceptive formulations, and metformin doses were not reported in the abstract. Clinical hirsutism scores showed no differences despite clear biochemical shifts, and adverse events or long-term clinical endpoints were not detailed.