Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials
- PMID: 32248801
- PMCID: PMC7132972
- DOI: 10.1186/s12905-020-00919-5
Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials
Abstract
Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting about 10% of women in reproductive age and associated with a variety of hormonal abnormalities, including hyperandrogenemia and infertility, all of which could lead to PCOS. Statins were previously introduced as a therapeutic option for reducing testosterone levels in women with PCOS, either alone or in combination. The aim of this study is to evaluate the effectiveness of different statins alone or in combination with metformin in reducing testosterone levels in women with PCOS.
Methods: Medline, Embase, and clinicaltrials.gov were searched for studies that investigated the efficacy of statins, metformin, spironolactone, or combined oral contraceptives (COCs), individually or in combination, in reducing the testosterone level in patients with PCOS. The search was limited to randomized clinical trials and conducted according to the preferred reporting items for systematic reviews and meta-analyses - extension statement for network meta-analyses (PRISMA-NMA). The quality of included studies was assessed using the Cochrane Collaboration risk of bias (RoB) assessment tool. A frequentist network meta-analysis using random-effects models was used to assess the efficacy in reducing testosterone level and were expressed as odds ratios (OR) and 95% credible interval (95%Crl). All statistical analyses were performed using netmeta Version 1.0 on R statistical package.
Result: Nine RCTs involving 613 patients were included. Atorvastatin showed greater reduction in testosterone level compared to COC (MD -2.78, 95%CrI -3.60, -1.97), spironolactone plus metformin (MD -2.83, 95%CrI -3.80, -1.87), simvastatin (MD -2.88, 95%CrI -3.85, -1.92), spironolactone (MD -2.90, 95%CI -3.77, -2.02), simvastatin plus metformin (MD -2.93, 95%CrI -3.79, -2.06), metformin (MD -2.97, 95%CrI -3.69, -2.25), lifestyle modification (MD -3.02, 95%CrI -3.87, -2.18), and placebo (MD -3.04, 95%CrI -3.56, -2.53).
Conclusion: Atorvastatin was found to be more effective than the other management strategies in reducing the total testosterone level for patients with PCOS. Future studies should focus on the optimal dose.
Keywords: Contraceptives; Metformin; PCOS; Spironolactone; Statins; Testosterone.
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
Similar articles
-
Comparison of different drug for reducing testosterone levels in women with polycystic ovary syndrome: A systematic review and network meta-analysis.Medicine (Baltimore). 2023 Oct 13;102(41):e35152. doi: 10.1097/MD.0000000000035152. Medicine (Baltimore). 2023. PMID: 37832133 Free PMC article.
-
The effectiveness of metformin, oral contraceptives, and lifestyle modification in improving the metabolism of overweight women with polycystic ovary syndrome: a network meta-analysis.Endocrine. 2019 May;64(2):220-232. doi: 10.1007/s12020-019-01860-w. Epub 2019 Mar 25. Endocrine. 2019. PMID: 30911997
-
Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome.Cochrane Database Syst Rev. 2020 Aug 13;8(8):CD005552. doi: 10.1002/14651858.CD005552.pub3. Cochrane Database Syst Rev. 2020. PMID: 32794179 Free PMC article.
-
Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial.Eur J Endocrinol. 2017 Nov;177(5):399-408. doi: 10.1530/EJE-17-0516. Eur J Endocrinol. 2017. PMID: 28912358 Clinical Trial.
-
Statin is a reasonable treatment option for patients with Polycystic Ovary Syndrome: a meta-analysis of randomized controlled trials.Exp Clin Endocrinol Diabetes. 2012 Jun;120(6):367-75. doi: 10.1055/s-0032-1304619. Epub 2012 May 25. Exp Clin Endocrinol Diabetes. 2012. PMID: 22639397
Cited by
-
Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS.Int J Mol Sci. 2020 Dec 15;21(24):9554. doi: 10.3390/ijms21249554. Int J Mol Sci. 2020. PMID: 33334002 Free PMC article. Review.
-
Statins for polycystic ovary syndrome in varying resource settings: a phenome-wide association study and evidence synthesis.Front Pharmacol. 2025 Aug 13;16:1562587. doi: 10.3389/fphar.2025.1562587. eCollection 2025. Front Pharmacol. 2025. PMID: 40808694 Free PMC article.
-
Spironolactone Versus Oral Contraceptive Pills in the Treatment of Adolescent Polycystic Ovarian Syndrome: A Systematic Review.Cureus. 2022 May 25;14(5):e25340. doi: 10.7759/cureus.25340. eCollection 2022 May. Cureus. 2022. PMID: 35774693 Free PMC article. Review.
-
Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men.Clin Endocrinol (Oxf). 2022 Dec;97(6):792-803. doi: 10.1111/cen.14803. Epub 2022 Aug 8. Clin Endocrinol (Oxf). 2022. PMID: 35902376 Free PMC article.
-
The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.Reprod Biol Endocrinol. 2021 Dec 20;19(1):189. doi: 10.1186/s12958-021-00863-5. Reprod Biol Endocrinol. 2021. PMID: 34930305 Free PMC article.
References
-
- Kazerooni T, Shojaei-Baghini A, Dehbashi S, Asadi N, Ghaffarpasand F, Kazerooni Y. Effects of metformin plus simvastatin on polycystic ovary syndrome: a prospective, randomized, double-blind, placebo-controlled study. Fertil Steril. 2010;94:2208–2213. doi: 10.1016/j.fertnstert.2009.11.045. - DOI - PubMed
-
- Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab. 2008;93:4299–4306. doi: 10.1210/jc.2008-0461. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical