University of Oulu

Maria Forslund, Johanna Melin, Simon Alesi, Terhi Piltonen, Daniela Romualdi, Chau Thien Tay, Selma Witchel, Alexia Pena, Aya Mousa, Helena Teede, Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis, European Journal of Endocrinology, Volume 189, Issue 1, July 2023, Pages S1–S16,

Different kinds of oral contraceptive pills in polycystic ovary syndrome : a systematic review and meta-analysis

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Author: Forslund, Maria1,2; Melin, Johanna2,3; Alesi, Simon2;
Organizations: 1Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
2Monash Centre for Health Research & Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, VIC 3800, Australia
3Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, 00290 Helsinki, Finland
4Clinical Research Unit, Department of Obstetrics and Gynecology, Medical Research Centre, Oulu University Hospital, University of Oulu, 90029 Oulu, Finland
5Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
6Division of Pediatric Endocrinology, Department of UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, 15224 Pittsburgh, PA, United States
7Discipline of Paedriatics, The University of Adelaide and Robinson Research Institute, 5005 Adelaide, Australia
8Endocrine and Diabetes Units, Monash Health, 5246 Clayton, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Bioscientifica, 2023
Publish Date: 2023-10-06


Objective: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).

Design: A systematic review and meta-analysis was performed, Prospero CRD42022345640.

Methods: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.

Results: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.

Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.

Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33–0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05–1.20]) compared with conventional COCPs.

There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.

Conclusion: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.

Trial registration: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.

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Series: European journal of endocrinology
ISSN: 0804-4643
ISSN-E: 1479-683X
ISSN-L: 0804-4643
Volume: 189
Issue: 1
Pages: S1 - S16
DOI: 10.1093/ejendo/lvad082
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3123 Gynaecology and paediatrics
Funding: M.F. received funding from the Iris Foundation. J.M. received funding from the Medical Society of Finland and Orion Research Foundation. A.M. is supported by a biomedical research fellowship provided by the National Health and Medical Research Council (NHMRC) of Australia. H.T. is a NHMRC Medical Research Future Fund Practitioner Fellow.
Dataset Reference: All data used in this manuscript is secondary and can be found in the online versions of the published studies. Our own data synthesis of these manuscripts is available upon reasonable request to the corresponding author.
Copyright information: © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.