Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2021

Open Access 01-12-2021 | Atorvastatin | Research

The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials

Authors: Jianguo Chen, Chaoran Huang, Tongtong Zhang, Wuqing Gong, Xiaofeng Deng, Hua Liu, Jinbo Liu, Yuanbiao Guo

Published in: Reproductive Biology and Endocrinology | Issue 1/2021

Login to get access

Abstract

Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, − 0.76−− 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, − 0.97−− 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, − 1.13−− 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, − 1.49−− 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.
Literature
1.
Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25:1825–37.PubMedCrossRef
2.
Cooney LG, Dokras A. Cardiometabolic risk in polycystic ovary syndrome: current guidelines. Endocrinol Metab Clin N Am. 2021;50:83–95.CrossRef
3.
Cignarella A, Mioni R, Sabbadin C, Dassie F, Parolin M, Vettor R, Barbot M, Scaroni C. Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS. Int J Mol Sci. 2020;21(24):9554.
4.
Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36:487–525.PubMedPubMedCentralCrossRef
5.
Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian Hyperandrogenism revisited. Endocr Rev. 2016;37:467–520.PubMedPubMedCentralCrossRef
6.
Rodrigues JK, Navarro PA, Zelinski MB, Stouffer RL, Xu J. Direct actions of androgens on the survival, growth and secretion of steroids and anti-Müllerian hormone by individual macaque follicles during three-dimensional culture. Hum Reprod. 2015;30:664–74.PubMedPubMedCentralCrossRef
7.
Rosenfield RL, Ehrlich EN, Cleary RE. Adrenal and ovarian contributions to the elevated free plasma androgen levels in hirsute women. J Clin Endocrinol Metab. 1972;34:92–8.PubMedCrossRef
8.
Phillips TG, Slomiany WP, Allison R. Hair loss: common causes and treatment. Am Fam Physician. 2017;96:371–8.PubMed
9.
10.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91:456–88.PubMedCrossRef
11.
12.
Sokalska A, Piotrowski PC, Rzepczynska IJ, Cress A, Duleba AJ. Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability. J Clin Endocrinol Metab. 2010;95:5390–4.PubMedPubMedCentralCrossRef
13.
14.
Duleba AJ, Banaszewska B, Spaczynski RZ, Pawelczyk L. Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. Fertil Steril. 2006;85:996–1001.PubMedCrossRef
15.
16.
Almalki HH, Alshibani TM, Alhifany AA, Almohammed OA. 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. BMC Womens Health. 2020;20:68.PubMedPubMedCentralCrossRef
17.
Carmena R, Betteridge DJ. Diabetogenic action of statins: mechanisms. Curr Atheroscler Rep. 2019;21:23.PubMedCrossRef
18.
Koch CA, Krabbe S, Hehmke B. Statins, metformin, proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and sex hormones: Immunomodulatory properties? Rev Endocr Metab Disord. 2018;19:363–95.PubMedCrossRef
19.
Seyam E, Hefzy E. Long-term effects of combined simvastatin and metformin treatment on the clinical abnormalities and ovulation dysfunction in single young women with polycystic ovary syndrome. Gynecol Endocrinol. 2018;34:1073–80.PubMedCrossRef
20.
Rashidi B, Abediasl J, Tehraninejad E, Rahmanpour H, Sills ES. Simvastatin effects on androgens, inflammatory mediators, and endogenous pituitary gonadotropins among patients with PCOS undergoing IVF: results from a prospective, randomized, placebo-controlled clinical trial. J Investig Med. 2011;59:912–6.PubMedCrossRef
21.
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;94:2208–13.PubMedCrossRef
22.
Sathyapalan T, Kilpatrick ES, Coady AM, Atkin SL. The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. J Clin Endocrinol Metab. 2009;94:103–8.PubMedCrossRef
23.
Duleba AJ, Banaszewska B, Spaczynski RZ, Pawelczyk L. Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. J Fertility and Sterility. 2006;85(4):996-1001.
24.
Seyam E, Al Gelany S, Abd Al Ghaney A, Mohamed MAA, Youseff AM, Ibrahim EM, et al. Evaluation of prolonged use of statins on the clinical and biochemical abnormalities and ovulation dysfunction in single young women with polycystic ovary syndrome. Gynecol Endocrinol. 2017;34:589–96.PubMedCrossRef
25.
Raja-Khan N, Kunselman AR, Hogeman CS, Stetter CM, Demers LM, Legro RS. Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2011;95:1849–52.PubMedCrossRef
26.
Puurunen J, Piltonen T, Puukka K, Ruokonen A, Savolainen MJ, Bloigu R, et al. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013;98:4798–807.PubMedCrossRef
27.
Banaszewska B, Pawelczyk L, Spaczynski RZ, Duleba AJ. Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J Clin Endocrinol Metab. 2011;96:3493–501.PubMedPubMedCentralCrossRef
28.
Gao L, Zhao FL, Li SC. Statin is a reasonable treatment option for patients with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Exp Clin Endocrinol Diabetes. 2012;120:367–75.
29.
Yang S, Gu YY, Jing F, Yu CX, Guan QB. The effect of statins on levels of Dehydroepiandrosterone (DHEA) in women with polycystic ovary syndrome: a systematic review and Meta-analysis. Med Sci Monit. 2019;25:590–7.PubMedPubMedCentralCrossRef
30.
Celik O, Acbay O. Effects of metformin plus rosuvastatin on hyperandrogenism in polycystic ovary syndrome patients with hyperlipidemia and impaired glucose tolerance. J Endocrinol Invest. 2012;35(10):905-10.
31.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.
32.
Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:Ed000142.PubMed
33.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRef
34.
35.
36.
Sathyapalan T, Smith KA, Coady AM, Kilpatrick ES, Atkin SL. Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study. Ann Clin Biochem. 2012;49:80–5.PubMedCrossRef
37.
Claessen BE, Guedeney P, Gibson CM, Angiolillo DJ, Cao D, Lepor N, et al. Lipid Management in Patients Presenting with Acute Coronary Syndromes: a review. J Am Heart Assoc. 2020;9:e018897.PubMedPubMedCentralCrossRef
38.
Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society. Hum Reprod Update. 2012;18:146–70.PubMedCrossRef
39.
Fraison E, Kostova E, Moran LJ, Bilal S, Ee CC, Venetis C, et al. Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome. Cochrane Database Syst Rev. 2020;8:Cd005552.PubMed
40.
Barrionuevo P, Nabhan M, Altayar O, Wang Z, Erwin PJ, Asi N, et al. Treatment options for Hirsutism: a systematic review and network Meta-analysis. J Clin Endocrinol Metab. 2018;103:1258–64.PubMedCrossRef
41.
Somani N, Turvy D. Hirsutism: an evidence-based treatment update. Am J Clin Dermatol. 2014;15:247–66.PubMedCrossRef
42.
Ishihara F, Komatsu M, Yamada T, Aizawa T, Ichikawa K, Takasu N, et al. Role of dehydroepiandrosterone and dehydroepiandrosterone sulfate for the maintenance of axillary hair in women. Horm Metab Res. 1993;25:34–6.PubMedCrossRef
43.
Johannsson G, Burman P, Wirén L, Engström BE, Nilsson AG, Ottosson M, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab. 2002;87:2046–52.PubMedCrossRef
44.
Azzi L, El-Alfy M, Martel C, Labrie F. Gender differences in mouse skin morphology and specific effects of sex steroids and dehydroepiandrosterone. J Invest Dermatol. 2005;124:22–7.PubMedCrossRef
45.
Chen MJ, Chen CD, Yang JH, Chen CL, Ho HN, Yang WS, et al. High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome. Hum Reprod. 2011;26:227–34.PubMedCrossRef
46.
Timpatanapong P, Rojanasakul A. Hormonal profiles and prevalence of polycystic ovary syndrome in women with acne. J Dermatol. 1997;24:223–9.PubMedCrossRef
47.
Saleh BO. Role of growth hormone and insulin-like growth factor-I in hyperandrogenism and the severity of acne vulgaris in young males. Saudi Med J. 2012;33:1196–200.PubMed
48.
Seirafi H, Farnaghi F, Vasheghani-Farahani A, Alirezaie NS, Esfahanian F, Firooz A, et al. Assessment of androgens in women with adult-onset acne. Int J Dermatol. 2007;46:1188–91.PubMedCrossRef
49.
Smythe CD, Greenall M, Kealey T. The activity of HMG-CoA reductase and acetyl-CoA carboxylase in human apocrine sweat glands, sebaceous glands, and hair follicles is regulated by phosphorylation and by exogenous cholesterol. J Invest Dermatol. 1998;111:139–48.PubMedCrossRef
50.
Palmer MA, Blakeborough L, Harries M, Haslam IS. Cholesterol homeostasis: links to hair follicle biology and hair disorders. Exp Dermatol. 2020;29:299–311.PubMedCrossRef
51.
Sokalska A, Stanley SD, Villanueva JA, Ortega I, Duleba AJ. Comparison of effects of different statins on growth and steroidogenesis of rat ovarian theca-interstitial cells. Biol Reprod. 2014;90:44.PubMedPubMedCentralCrossRef
52.
Kaya C, Pabuccu R, Cengiz SD, Dünder I. Comparison of the effects of atorvastatin and simvastatin in women with polycystic ovary syndrome: a prospective, randomized study. Exp Clin Endocrinol Diabetes. 2010;118:161–6.PubMedCrossRef
Metadata
Title
The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors
Jianguo Chen
Chaoran Huang
Tongtong Zhang
Wuqing Gong
Xiaofeng Deng
Hua Liu
Jinbo Liu
Yuanbiao Guo
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2021
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-021-00863-5

Other articles of this Issue 1/2021

Reproductive Biology and Endocrinology 1/2021 Go to the issue

Research

Controlled ovarian stimulation should not be preferred for male infertility treated with intrauterine insemination: a retrospective study

Research

CircCRIM1 promotes ovarian cancer progression by working as ceRNAs of CRIM1 and targeting miR-383-5p/ZEB2 axis

Research

WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

Correction

Correction to: Psychological experience and coping strategies of patients in the Northeast US delaying care for infertility during the COVID-19 pandemic

Research

Individualized embryo selection strategy developed by stacking machine learning model for better in vitro fertilization outcomes: an application study

Research

Association of ABO blood groups with ovarian reserve, and outcomes after assisted reproductive technology: systematic review and meta-analyses