Effect of the combined oral contraceptive pill and/or metformin in the management of PCOS: a systematic review with meta-analyses.
Clin Endocrinol (Oxf). 2019 May 14;:
Authors: Teede H, Tassone EC, Piltonen T, Malhotra J, Mol BW, Peña A, Witchel SF, Joham A, McAllister V, Romualdi D, Thondan M, Costello M, Misso ML
BACKGROUND: Polycystic ovary syndrome (PCOS) has a prevalence of 8-13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aims to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines.
METHODS: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials (RCTs) which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritised as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal completed. Meta-analyses were conducted, where appropriate.
RESULTS: Fifty-six studies were eligible for inclusion. Outcomes prioritised by women and health professionals included: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference (MD) -4.02 [-5.23, -2.81], p <0.001); and COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], p <0.00001). In low quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], p= 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], p= 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], p= 0.03). COCP alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], p= 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were sub-grouped by BMI. CONCLUSIONS: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal, and metabolic outcomes, especially for women with BMI≥25 kg/m². There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin. This article is protected by copyright. All rights reserved. PMID: 31087796 [PubMed - as supplied by publisher]