# Regulation of stress and depression by hormonal contraceptives

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $42,459

## Abstract

PROJECT SUMMARY
 Oral contraceptives (OCs), the most common type of hormonal contraceptives, are taken by more than 150
million people worldwide at any given time. For approximately 10% of users, OCs trigger severe mood-related
adverse consequences, including depression and anxiety. The current project will use a mouse model to
identify how OCs modulate the hypothalamic-pituitary-adrenal (HPA) axis and contribute to increased
vulnerability – or resilience – to depression. A dysregulated stress response is a key aspect of depression, and
there is consistent evidence that OCs blunt the HPA axis. Central mineralocorticoid receptors (MR) and
glucocorticoid receptors (GR) activity control the stress response via negative feedback loops. FK506-binding
protein 51 (FKBP5) regulates the balance between MR and GR, and is expressed throughout the
hypothalamus, an essential part of the stress response; and the hippocampus, which is implicated in the
effects of stress on affective regulation and depression. Therefore, this project will determine changes in
hypothalamic and hippocampal FKBP5, GR, and MR activity, their causal role in blunting systemic stress
responses, and how stress and OCs interact in individuals at risk for depression. We will integrate biochemical,
molecular, behavioral, and CRISPR/Cas9 genetic techniques to address these questions. The overall goal of
this project is to systematically study the impact of OCs on specific psychological and physiological
components of stress and depression using a mouse model of OC exposure. The central hypothesis of this
project is that OC-triggered depression is caused by molecular changes that regulate the stress response, only
in individuals with a pre-existing vulnerability to depression. At the end of this project, a molecular basis for
more targeted interventions will be delineated to understand the mechanisms of OCs effects on the stress
response and depression. This research can be applied directly to the improvement of contraceptives for all
hormonal contraceptive users and will transform the understanding and treatment of OC-induced mental
illness, including depression and anxiety. Furthermore, the current project will pave the way for a personalized
approach for prescribing OCs to limit adverse effects and enhance benefits.

## Key facts

- **NIH application ID:** 10824648
- **Project number:** 1F31HD114532-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kristen Schuh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,459
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824648

## Citation

> US National Institutes of Health, RePORTER application 10824648, Regulation of stress and depression by hormonal contraceptives (1F31HD114532-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10824648. Licensed CC0.

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