Abstract
Purpose :
The etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a pre-diagnostic plasma steroid hormone metabolomics signature associated with XFG.
Methods :
We conducted a 1:1 matched case-control study nested within the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-up Study (HPFS). We collected blood samples in 1989-’90 (NHS), 1996-‘99 (NHSII), and 1993-’95 (HPFS). We identified 217 incident XFG cases through 2016 (average time to diagnosis from blood draw = 11.8 years) who self-reported glaucoma and were confirmed as XFG cases with medical records. Controls (n=217) were matched on age, sex, and fasting status. We profiled 16 plasma endogenous steroids using liquid chromatography-mass spectrometry: 3 progestogens, 4 mineralocorticoids, 2 glucocorticoids, 5 androgens, and 2 estrogens. We log-transformed the assay values and used multiple conditional logistic models to obtain multivariable adjusted relative risks (MVRRs) for analyses.
Results :
The mean age of cases at diagnosis was 70 years; 86% were women and >99% were Caucasian; controls reported eye exams as of the matched cases’ index date. While we observed no significant associations with progestogens, mineralocorticoids, estrogens, and glucocorticoids, we observed nominally significant associations between higher testosterone and testosterone metabolite levels and lower XFG risk for 3 of the 5 androgens: 11-ketotestosterone (MVRRper one ln(ng/mL) increase=0.48; 95% CI: 0.30-0.77), 11β-hydroxyandrostenedione (MVRRper one ln(ng/mL) increase=0.67; 95% CI: 0.46-0.98), and testosterone (MVRRper one ln(ng/mL) increase=0.65; 95% CI: 0.42-0.998). Similar inverse associations were observed in both men and women.
Conclusions :
In plasma from a decade before diagnosis, higher testosterone metabolites were inversely associated with XFG risk in both men and women.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.