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Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials

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Abstract

Context

Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess.

Aim

To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS.

Data source

We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021.

Data synthesis

Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results

Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: − 0.33; 95% CI  − 0.49 to  − 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  − 1.34 to  − 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  − 0.47; 95% CI  − 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  − 0.37 µg/dL; 95% CI  − 0.05 to  − 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  − 1.67; 95% CI  − 2.27 to  − 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54–151.05, p < 0.0001, very low-grade evidence) were observed.

Conclusion

Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects.

PROSPERO registration No

CRD42020178783.

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Data availability

The datasets generated and analysed for this review are available upon compelling request to the authors.

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Acknowledgements

We thank Dr Gamila Hassan at the National Medical Library (UAEU) for her support in locating and uploading full-text papers to Covidence for screening.

Funding

This systematic review was completed as part of a self-funded PhD project for MA, and no external fund was received.

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Authors and Affiliations

  1. Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre, The University of Hull, Hull York Medical School (HYMS), Hull, UK

    Mohammed Altigani Abdalla, Najeeb Shah, Harshal Deshmukh & Thozhukat Sathyapalan

  2. Biotechnology Research Centre, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  3. Applied Biomedical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  4. School of Medicine, the University of Western Australia, Perth, WA, Australia

    Amirhossein Sahebkar

  5. College of Medicine and Health Sciences, the National Medical Library, United Arab Emirates University, Abu Dhabi, United Arab Emirates

    Linda Östlundh

  6. College of Medicine and Health Sciences, Institute of Public Health, United Arab Emirates University, Al Ain, United Arab Emirates

    Rami H. Al-Rifai

  7. School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Kingdom of Bahrain

    Stephen L. Atkin

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  1. Mohammed Altigani Abdalla
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  8. Thozhukat Sathyapalan
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Contributions

MA: designed the review, completed the database searches, assessed the quality, extracted, collected, and analysed the data, written, revised, and edited the final manuscript. NS: assessed the quality, extracted and collected the data, and revised and edited the final manuscript. HD: revised and edited the final manuscript. AS: revised and edited the final manuscript. LÖ: developed and performed the systematic search, assessed for predatory journals and revised and edited the final manuscript. RHA: revised and edited the final manuscript. SA: revised and edited the final draft of the manuscript. Finally, TS acted as a mediator for assessing the quality of the evidence, supervised the study, participated in the critical discussion, revised and edited the final manuscript.

Corresponding author

Correspondence to Thozhukat Sathyapalan.

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Abdalla, M.A., Shah, N., Deshmukh, H. et al. Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials. Arch Gynecol Obstet 307, 1347–1376 (2023). https://doi.org/10.1007/s00404-022-06549-6

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