Hormonal mechanisms of women’s risk in the face of traumatic stress

J Jennifer S. Stevens M Madeline Davis (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) C Cecilia A. Hinojosa (Department of Psychology, University of New Mexico) R Rebecca Hinrichs (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) A Alyssa R. Roeckner (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) K Katelyn I. Oliver (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) L Linzie Taylor (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) J Justin L. C. Santos (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) H Helena Zeleke (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) E Esther Lin (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) K Kristina Dahlgren (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) T Timothy D. Ely (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) A Amy R. Murphy (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) C Colin Johnson (Department of Chemistry and Biochemistry) D Dasani DelRosario (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) N Natalie Merrill (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine) X Xing Zhang (State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry) K Kelly F. Ethun (Biomarkers Core, Emory National Primate Research Center, Emory University) M Marisa Young (Department of Gynecology and Obstetrics, Emory University School of Medicine) A Andrea Braden (Department of Gynecology and Obstetrics, Emory University School of Medicine) N Nicole R. Nugent A Abigail Powers S Sanne J. H. van Rooij K Kim Wallen (Department of Psychology, Emory College) V Vasiliki Michopoulos

Abstract

Women are underrepresented in biomedical research, limiting understanding of their disproportionate rates of stress-related disorders. Although men experience more trauma, women are twice as likely to develop posttraumatic stress disorder (PTSD). We tested whether ovarian hormones contribute to this disparity via their influence on threat-related brain activity. In a randomized, double-blind crossover study of 110 young women, we examined how exogenous estradiol (E2) modulates threat neurocircuitry, timed precisely to ovarian phase. E2 increased engagement of the ventromedial prefrontal cortex and, in the early luteal phase, reduced central and corticomedial amygdala reactivity to threat in women with little trauma history, but not those with PTSD. Fluctuations in E2 therefore modulate neural responses to threat, and sensitivity to these fluctuations may underlie women’s heightened vulnerability to stress-related disorders.

Article Details

Volume / Issue Vol. 122, Issue 51
Published December 23, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (25)

J

Jennifer S. Stevens

M

Madeline Davis

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

C

Cecilia A. Hinojosa

Department of Psychology, University of New Mexico

R

Rebecca Hinrichs

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

A

Alyssa R. Roeckner

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

K

Katelyn I. Oliver

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

L

Linzie Taylor

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

J

Justin L. C. Santos

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

H

Helena Zeleke

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

E

Esther Lin

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

K

Kristina Dahlgren

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

T

Timothy D. Ely

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

A

Amy R. Murphy

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

C

Colin Johnson

Department of Chemistry and Biochemistry

D

Dasani DelRosario

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

N

Natalie Merrill

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine

X

Xing Zhang

State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry

K

Kelly F. Ethun

Biomarkers Core, Emory National Primate Research Center, Emory University

M

Marisa Young

Department of Gynecology and Obstetrics, Emory University School of Medicine

A

Andrea Braden

Department of Gynecology and Obstetrics, Emory University School of Medicine

N

Nicole R. Nugent

A

Abigail Powers

S

Sanne J. H. van Rooij

K

Kim Wallen

Department of Psychology, Emory College

V

Vasiliki Michopoulos