University of Oulu

Teede H, Tassone EC, Piltonen T, etal. Effect of the combined oral contraceptive pill and/ormetformin in the management of polycystic ovary syndrome:A systematic review with meta‐analyses. Clin Endocrinol (Oxf). 2019;91:479–489. https://doi.org/10.1111/cen.14013

Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome : a systematic review with meta‐analyses

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Author: Teede, Helena1,2; Tassone, Eliza C.1; Piltonen, Terhi3;
Organizations: 1Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
2Department of Diabetes and Vascular Medicine, Monash Health, Clayton, Victoria, Australia
3Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
4Rainbow Hospital & Malhotra Nursing and Maternity Home, Agra, India
5Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
6Discipline of Paediatrics, Endocrinology and Diabetes Department, Women's and Children's Hospital, The University of Adelaide and Robinson Research Institute, North Adelaide, South Australia, Australia
7Peadiatric Endocrinology, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania
8Polycystic Ovary Association of Australia, Sydney, New South Wales, Australia
9Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
10HARP Family Medical, Kew, Victoria, Australia
11University of New South Wales, Sydney, New South Wales, Australia
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2019091828601
Language: English
Published: John Wiley & Sons, 2019
Publish Date: 2020-05-14
Description:

Abstract

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 aimed 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 which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized 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 was completed. Meta‐analyses were conducted, where appropriate.

Results: Fifty‐six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: 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); 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). Combined oral contraceptive pill 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 subgrouped 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.

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Series: Clinical endocrinology
ISSN: 0300-0664
ISSN-E: 1365-2265
ISSN-L: 0300-0664
Volume: 91
Issue: 4
Pages: 479 - 489
DOI: 10.1111/cen.14013
OADOI: https://oadoi.org/10.1111/cen.14013
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: The guideline was primarily funded by the National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine.
Copyright information: © 2019 John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Teede H, Tassone EC, Piltonen T, etal. Effect of the combined oral contraceptive pill and/ormetformin in the management of polycystic ovary syndrome:A systematic review with meta‐analyses. Clin Endocrinol (Oxf). 2019;91:479–489. https://doi.org/10.1111/cen.14013, which has been published in final form at https://doi.org/10.1111/cen.14013. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.