# Reproductive Consequences of Steroid Hormone Administration

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $522,435

## Abstract

Recent data estimates 1.4 million transgender adults and 150,000 transgender adolescents live in the United
States, many of whom are on cross-sex hormone therapy with estradiol or testosterone (T). National and
international medical organizations recommend fertility preservation counseling prior to initiation of cross-sex
hormone therapy, based on an assumption of fertility loss. However, the impact of long-term cross-sex
hormone therapy on reproductive health is largely unknown, particularly in transgender men (female-to-
male or FTM). The available human studies suggest ovarian changes from cross-sex T therapy, but are
observational studies, with conflicting results. Moreover, there is a lack of data on the fecundity of T-treated
transgender men, and there have been no studies that address the reversibility of T-induced changes after
cessation of T for reproductive purposes. There are also no studies on future reproductive consequences of the
treatment paradigm for transgender adolescents, in which GnRHa is initiated in the early peripubertal period to
suppress further pubertal progression prior to transitioning directly to T therapy (GnRHa-T). None of the existing
animal models that address the effect of androgens on reproductive function in females are directly applicable
to the clinical paradigm of cross-sex T therapy in transgender men or GnRHa-T therapy in transgender
adolescents. To address this knowledge gap, we have developed a mouse model to mimic T treatment for
FTM gender transition. These mice manifest defects in ovarian architecture and have altered folliculogenesis.
This model provides a powerful tool to clarify the effects of T therapy on reproductive phenotype and function, in
a manner not possible in humans. The objective of the proposed studies is to use the FTM mouse model to
investigate the effects of cross-sex T treatment on reproductive phenotype and function, and determine the
reversibility of these effects following cessation of T. Our central hypothesis is that T therapy will adversely
affect ovarian architecture and fertility, but that fertility can be recovered with cessation of T, without adverse
reproductive effects in offspring. To test this hypothesis, we will examine the reversibility of postpubertal T
administration in female mice, mimicking FTM gender transition, on reproductive phenotype (AIM 1), and
examine fertility during and after cessation of long-term testosterone therapy, including reproductive phenotype
in offspring (AIM 2). In an exploratory aim, we will examine the reproductive consequences of testosterone
administration after pretreatment with peripubertal GnRHa, mimicking FTM cross-sex hormone therapy in
adolescents, on reproductive phenotype and fertility (AIM 3). This proposal challenges the status quo of
recommending fertility preservation prior to cross-sex T therapy, and will lay the foundation for further
translational studies. Our long-term goal is to provide the necessary data for evidence-...

## Key facts

- **NIH application ID:** 10165769
- **Project number:** 5R01HD098233-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Molly Bennette Moravek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $522,435
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165769

## Citation

> US National Institutes of Health, RePORTER application 10165769, Reproductive Consequences of Steroid Hormone Administration (5R01HD098233-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165769. Licensed CC0.

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