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Meta-Analysis
. 2024 Jan 18;109(2):e817-e836.
doi: 10.1210/clinem/dgad465.

Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis

Johanna Melin  1   2 , Maria Forslund  1   3 , Simon Alesi  1 , Terhi Piltonen  4 , Daniela Romualdi  5 , Poli Mara Spritzer  6 , Chau Thien Tay  1 , Alexia Pena  7 , Selma Feldman Witchel  8 , Aya Mousa  1 , Helena Teede  1   9
Affiliations
Meta-Analysis

Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis

Johanna Melin et al. J Clin Endocrinol Metab. .

Abstract

Context: Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.

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 (RCTs).

Data extraction: We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.

Data synthesis: The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs 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 some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).

Keywords: combined oral contraceptive pill; hirsutism; meta-analysis; metformin; polycystic ovary syndrome; weight.

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Figures

Figure 1.
Figure 1.
Included studies are shown in the PRISMA flowchart. The search was performed for 3 medical treatments (combined oral contraceptive pills [COCP], metformin, and anti-androgens) as part of the update of the PCOS guidelines. Results comparing COCP, metformin, and combined COCP and metformin were included in this systematic review.
Figure 2.
Figure 2.
Risk of bias assessments of the included studies.
See this image and copyright information in PMC

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