# Sex hormones and post-traumatic stress disorder (PTSD)

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $394,561

## Abstract

Project summary
The untreated burden of post-traumatic stress disorder (PTSD) in the United States is a massive contributor to
healthcare budgets in both the military and civilian sectors, and better treatment and prevention methods are
needed. Fortunately, awareness of PTSD among military service members has grown in recent years, and
yet, there is a hidden epidemic of PTSD among civilians and women. Women experience PTSD at about twice
the rate of men (11% vs. 5%), but the causes for this sex difference are largely unknown. It has long been
suspected that sex hormones play a major role in development of – and also potentially protection from –
PTSD and other mental health disorders. This project will provide the largest ever study of sex hormone
effects on PTSD and the related mental health outcomes of depression and anxiety disorders. Whereas
studies in the past were limited by small sample sizes and results were inconclusive, this investigation will use
a massive sample size of approximately 500,000 participants to answer questions about two well-known sex
hormones (testosterone and estradiol) and three psychiatric outcomes (PTSD, depression, and anxiety
disorders). These variables were measured in the UK Biobank, and we have been granted access to the data
to study sex hormone effects on mental health outcomes and to study genetic effects underlying both sex
hormone levels and mental health disorders. The completion of this work will reveal whether rates of mental
health disorders vary with testosterone and estradiol levels. It may be the case that levels of hormones that
are both too high and too low are problematic. Given this reality, we will use sophisticated regression and
machine learning techniques, and therefore we will be able to detect linear and non-linear relationships
between sex hormones and PTSD, depression, and anxiety disorders. The sample size and study design
make this the most powerful study conducted to date, and the results will be generalizable to diverse
populations. In addition to the outcomes mentioned above, we will further explore genetic effects underlying
relationships between sex hormones and mental health disorders. To do this, we will conduct genome-wide
association studies (GWAS) of both testosterone and estradiol. We will then make polygenic scores for
testosterone and estradiol, yielding genetic proxies of sex hormone levels which can be used in studies in
which sex hormones have not been measured. Finally, we will test for shared genetic effects between genetic
effects on sex hormones and genetic effects on psychiatric disorders in order to better understand the etiology
of these common, debilitating, and inadequately treated mental health disorders. Taken together, these
findings will provide critical foundational knowledge relevant to clinical trials which are currently testing
testosterone and estradiol as treatments for PTSD, depression, and anxiety disorders. These results will also
provide actionabl...

## Key facts

- **NIH application ID:** 10410486
- **Project number:** 5R01MH123486-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Laramie Duncan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,561
- **Award type:** 5
- **Project period:** 2020-08-14 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410486

## Citation

> US National Institutes of Health, RePORTER application 10410486, Sex hormones and post-traumatic stress disorder (PTSD) (5R01MH123486-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10410486. Licensed CC0.

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