Faculty, Staff and Student Publications

Language

English

Publication Date

7-1-2025

Journal

Gynecologic Oncology

DOI

10.1016/j.ygyno.2025.05.013

PMID

40482607

PMCID

PMC12885142

PubMedCentral® Posted Date

2-10-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and by histotype using Kaplan-Meier curves and Cox proportional hazards models.

Results: Overweight/obesity was associated with higher risk of ER- tumors (OR:1.53, 95 % I:1.18-1.98). Hysterectomy was associated with greater risk of ER+ tumors (OR:4.99, 95 % CI:4.27-5.83), which varied by AR expression (Pheter=0.003). Postmenopause was associated with a higher risk of PR- tumors (OR 1.52, 95 % CI 1.26-1.83), which varied based by AR (Pheter < 0.001) and ER (Pheter < 0.001) expression. Gravidity, oral contraception duration, and breastfeeding duration showed differing dose-response relationships according to AR/ER/PR expression. Hormone therapy use, postmenopause, physical inactivity, and being obese/overweight prior to diagnosis were differentially associated with survival based on AR/ER/PR expression and histotype.

Conclusion: EOC has varying risk and prognostic profiles depending on both histotype and AR/ER/PR expression. Biological mechanisms underlying the association between hormonally-linked factors and EOC need to be studied by both histotypes and by AR, ER, and PR expression.

Keywords

Humans, Female, Ovarian Neoplasms, Receptors, Androgen, Receptors, Progesterone, Middle Aged, Carcinoma, Ovarian Epithelial, Estrogen Receptor alpha, Aged, Risk Factors, Receptors, Estrogen, Adult, Neoplasms, Glandular and Epithelial, Obesity, Case-Control Studies, Epithelial ovarian cancer, Hormonal factors, Hormone receptor, Risk, Survival, androgen receptor, estrogen receptor, progesterone receptor

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