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Steroid Metabolome Profiling Identifies a Unique Androgen Hormone Signature Associated with Endometriosis

Simitsidellis, I.; Ainslie, R. J.; Taylor, A.; Gilligan, L. C.; Shaheen, F.; Blanke, S.; Anderson, C.; Hapangama, D.; Arlt, W.; Horne, A. W.; Saunders, P. T.; Gibson, D. A.

2025-05-25 sexual and reproductive health
10.1101/2025.05.24.25328281 medRxiv
Show abstract

Endometriosis is a chronic, hormone-dependent condition that affects 190 million women worldwide. There are no validated biomarkers for endometriosis and this delays diagnosis and treatment. We performed serum steroid metabolome profiling in healthy controls (n=57) and women with laparoscopically-confirmed endometriosis (n=159) using liquid chromatography-tandem mass spectrometry. Women with endometriosis had a distinct steroid signature characterised by increased concentrations of classic and 11-oxygenated androgens, and altered metabolism associated with 11-ketotestosterone production. Metabolomic data were used to generate a supervised machine learning model to predict diagnostic outcome. ROC curve analysis demonstrated robust discrimination between healthy controls and endometriosis patients (AUC=0.99) with 96.84% positive-, and 92.86% negative-predictive power. Data were partitioned into train and validation groups, and a refined model identified >95% of endometriosis patients in a blinded sample set. These data reframe endometriosis as an androgen-dominant condition and present a unique opportunity to develop novel diagnostic approaches using 11-oxygenated androgens as biomarkers.

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