# Androgens and Nonalcoholic Steatohepatitis: The Role of Male Sex Hormones in Women with NASH

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $198,882

## Abstract

PROJECT SUMMARY
 Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is projected to be the
leading cause of cirrhosis, primary liver cancer, and the leading indication for liver transplantation in the United
States (U.S.) within the next few years. Women are at disproportionate risk for NASH, with approximately 15
million U.S. women affected, and therapeutic options in NASH are limited. There is an urgent need to
understand risk factors for NASH and its progression in women, and sex hormones may provide a missing link.
While estrogens have been shown to protect against NASH progression, emerging data support the detrimental
role of androgens in this disease. Our preliminary data demonstrate a strong and independent association of
testosterone levels with risk of imaging-confirmed NAFLD in women, as well as a strong association between a
clinical marker of hyperandrogenism and advanced NASH fibrosis on biopsy. No studies to date have
characterized comprehensive sex hormone levels in women to investigate the association of androgen levels, or
interplay between androgens and estrogens, on the natural history of NASH in women. To address this
knowledge gap I will leverage the NIDDK-funded multicenter NASH Clinical Research Network (NASH CRN
cohort) to perform sex hormone measures on banked serum to investigate their association with histologic
measures of NASH severity and progression. I will then conduct a pilot randomized controlled trial to assess the
feasibility, safety and preliminary efficacy of androgen receptor antagonist therapy on NASH progression in
women. I hypothesize that higher androgen levels will be associated with worse NASH severity and
progression, and these associations will be stronger in women with lower estrogen.
 My long-term goal is to lead multidisciplinary research merging reproductive endocrinology, women's
health, and liver disease, with specific expertise in the influence of sex hormones and hormone modifying
therapy on liver disease in women. I have a strong background in hepatitis C virus (HCV) in women, including
recent research on the role of sex hormones in HCV fibrosis. I am now expanding my research to study
androgens in NASH given the profound public health implications of NASH, the disproportionate risk of NASH
in women, and emerging data linking androgens to fat-related liver injury in women. This study may help to
identify women at risk for NASH progression while elucidating a novel mechanism for therapeutic intervention. I
have assembled an extraordinary multidisciplinary mentorship team including my primary mentor in NASH, Dr.
Terrault, my reproductive endocrinology mentor, Dr. Cedars, and Dr. Bacchetti as my biostatistical mentor.
With a detailed five-year research and training plan I will develop content expertise in clinical trials,
reproductive endocrinology and NASH pathobiology, while obtaining preliminary data for a larger, R01 trial
investigating anti-androgen therap...

## Key facts

- **NIH application ID:** 10205043
- **Project number:** 5K23DK111944-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Monika Sarkar
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,882
- **Award type:** 5
- **Project period:** 2017-07-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205043

## Citation

> US National Institutes of Health, RePORTER application 10205043, Androgens and Nonalcoholic Steatohepatitis: The Role of Male Sex Hormones in Women with NASH (5K23DK111944-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10205043. Licensed CC0.

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