ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1562587
Statins for polycystic ovary syndrome in varying resource settings: A phenome-wide association study and evidence synthesis
Provisionally accepted
Laura A Zahn1
Rebecca N. Jerome1*Taylor D Budine1Jana K Shirey-Rice1
Meghan Joly1
Robert Steven Wallis2Gordon R Bernard1Kenneth J Holroyd1Jill M Pulley1- 1Vanderbilt University Medical Center, Nashville, United States
- 2Aurum Institute, Johannesburg, South Africa
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: There are many diseases prevalent around the globe that lack accessible and safe treatment options. Through Vanderbilt University Medical Center's and Repurposing Essential Medicines Internationally program (Project Remedi), we aim to identify novel therapeutic uses for medications already approved and on the World Health Organization's (WHO) Essential Medicines List (EML). We explored additional uses for simvastatin, an oral 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is on the EML and may have additional therapeutic use outside of hypercholesterolemia.Methods: We conducted a phenome wide association study (PheWAS) of a 3-hydroxy-3methylglutaryl-CoA reductase (HMGCR) gene single nucleotide polymorphism (SNP) Ile638Val in 35,000 patient samples to identify novel uses for simvastatin. We then assessed biologic rationale and existing clinical evidence base related to novel phenotypes for simvastatin use for key PheWAS results.Results: PheWAS of HMGCR variants identified a novel signal related to ovarian disease, in addition to a validating signal related to lipid dysfunction. Review of the literature substantiated involvement of HMG-CoA reductase signaling in hormone synthesis and posited involvement of dysfunction in this pathway in the development of polycystic ovary syndrome (PCOS).Synthesis of the literature regarding use of statins supported the role of these agents in improvement of symptoms and quality of life in women affected by PCOS who are not pregnant or trying to conceive, with a safety profile similar to this agent's use in hyperlipidemia.Conclusions: Given the evidence supporting safety and efficacy of simvastatin for PCOS management, the widespread availability on the EML and affordability worldwide, simvastatin is a promising therapeutic avenue for PCOS. A large-scale efficacy trial would be valuable in further substantiating this use. Repurposing simvastatin, a widely available medicine, can provide clinicians and patients with an additional strategy for PCOS, especially in areas where medical care is limited.Statins for polycystic ovary syndrome in varying resource settings: A phenome-wide association study and evidence synthesis 1
Keywords: Simvastatin, Statins, HMG-CoA reductase inhibitors, Polycystic Ovary Syndrome, PheWAS, global health
Received: 08 May 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Zahn, Jerome, Budine, Shirey-Rice, Joly, Wallis, Bernard, Holroyd and Pulley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rebecca N. Jerome, Vanderbilt University Medical Center, Nashville, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.