# Mechanisms of actions(s) of simvastatin in uterine leiomyoma

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $704,878

## Abstract

PROJECT SUMMARY
Uterine fibroids represent a significant medical challenge with an immense economic burden. With an
estimated incidence of 70-80% by the age of 50, they are the most common tumors of the female reproductive
tract and the estimated annual costs in the US are $5.9-34.4 billion. Current hormonal treatments have
limitations; therefore, there is an urgent need for new non-hormonal therapies.
We recently discovered the following: 1) statin (HMG-CoA reductase inhibitors currently used in treating
hypercholesterolemia) use was associated with a lower risk of uterine fibroids and fibroid-related symptoms in
a retrospective study; 2) simvastatin inhibited tumor growth in a patient-derived xenograft animal model; 3)
simvastatin inhibited proliferation and induced apoptosis in human fibroid cells in vitro; and most importantly, 4)
the antiproliferative effects of simvastatin and ulipristal acetate on fibroid cells were synergistic. Thus, further
evaluation of simvastatin as a treatment for uterine fibroids is needed. While statins are FDA-approved and
are in common usage, their effect on fibroids has not been systematically evaluated. We hypothesize that
simvastatin has therapeutic effects on leiomyomas, through inhibiting the mevalonate pathway
including isoprenoid intermediates necessary for Ras and Rho activation and these effects operate
synergistically with ulipristal acetate through modulation of progesterone signaling. The objective of this
study is to examine simvastatin as an anti-leiomyoma therapeutic and determine the mechanisms of these
effects, in vivo and in vitro.
The first aim is a phase II randomized clinical trial to determine feasibility, safety and preliminary clinical
efficacy of simvastatin in uterine leiomyoma. The second aim is a translational study to characterize the
molecular, cellular and histologic effects of simvastatin on leiomyoma tissues from Aim 1. We expect
that simvastatin inhibits proliferation; induces apoptosis, inhibits stem cell proliferation; and alters ECM
structure and mechanical signaling in leiomyomas. The third aim will focus on the mechanism(s) of
simvastatin’s effects on leiomyoma, including stem cells, growth factor signaling, extracellular matrix
production, and sex steroid biosynthesis and signaling. We also examine the mechanisms of synergistic action
between simvastatin and ulipristal acetate through modulation of progesterone signaling. The successful
completion of this project is the next step toward implementation of a new non-hormonal treatment for uterine
fibroids and provides insight into novel therapeutic modulation of critical fibroid pathways. This research
proposal is highly response to the RFA and the overall mission of NICHD and NIH.

## Key facts

- **NIH application ID:** 10470204
- **Project number:** 5R01HD094380-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mostafa A. Borahay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $704,878
- **Award type:** 5
- **Project period:** 2018-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470204

## Citation

> US National Institutes of Health, RePORTER application 10470204, Mechanisms of actions(s) of simvastatin in uterine leiomyoma (5R01HD094380-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10470204. Licensed CC0.

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