Metformin and combined oral contraceptive pills in the management of polycystic ovary syndrome: a systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is affecting more than every tenth woman.

OBJECTIVE: As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin and combination treatment were evaluated.

DATA SOURCES: Ovid Medline, Embase, PsycINFO, All EBM and CINAHL were searched.

STUDY SELECTION: Women with PCOS included in randomized controlled trials (RCT).

DATA EXTRACTION: We calculated mean differences (MD) and 95% confidence intervals (CI) regarding anthropometrics, metabolic and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE was performed.

DATA SYNTHESIS: The search identified 1660 publications, 36 RCTs were included. For hirsutism no differences were seen when comparing metformin versus COCP, nor when comparing COCP versus combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08, 95% CI 4.81; 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/l, 95% CI -174.46; -62.75) and testosterone (0.48 nmol/l,95% CI 0.32; 0.64) compared with COCP. COCP was inferior for FAI (0.58, 95% CI 0.36; 0.80) and SHBG (-16.61 nmol/L, 95% CI -28.51; -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/l, 95%CI -40.65; -13.59) and triglycerides (-0.15 mmol/l, 95%CI -0.29; -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/l, 95%CI 7.79; 26.26) and insulin resistance (0.44, 95%CI 0.17; 0.70) compared with combination treatment.

CONCLUSIONS: The choice of metformin or COCP treatment should be based on symptoms, noting that there are some biochemical benefits from combination treatment, targeting both major endocrine disturbances seen in PCOS; hyperinsulinemia and hyperandrogenism.