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Editors Selection IGR 24-1

Risk Factors: Is higher Testosterone predisposing women to POAG?

Comment by Thasarat Vajaranant on:

109249 Higher testosterone is associated with open-angle glaucoma in women: a genetic predisposition?, Vergroesen JE; Kaynak A; Aribas E et al., Biology of sex differences, 2023; 14: 27

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Understanding sex-specific risk factors for primary open-angle glaucoma (POAG) is vital, as differences in pathophysiology may lead to distinct risks for men and women. While the influence of estrogen on glaucoma is well-documented in women, the impact of testosterone remains understudied. Leveraging a rich database in the prospective, population-based Rotterdam Study (RS I, II, and III), Vergroesen and colleagues investigated the role of testosterone in glaucoma. Interestingly, they observed sex differences in the effects of testosterone on incident OAG (iOAG), intraocular pressure (IOP), retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform (GCL+). Based solely on the glaucomatous visual field abnormalities, the incidence of OAG was 2.4% (187 participants out of 7898 participants). The final adjusted analyses demonstrated that the genetic risk scores (GRS) for higher testosterone, a proxy for genetic predisposition, increased iOAG in both men and women by approximately 2.5-fold. However, the higher serum testosterone only doubled the iOAG risk in women, not men. Additionally, serum testosterone had diverse effects on IOP, RNFL, and GCL+ in a limited subgroup of men and women (~255 to 709). Specifically, the influence of testosterone on these parameters in men remained unclear. However, in women, elevated testosterone was associated with increased IOP and thinner RNFL and GCL+, suggesting a potential underlying mechanism.

This study offers initial evidence suggesting a genetic predisposition for elevated testosterone and glaucoma risk in both sexes. The association between higher serum testosterone and OAG in women aligns with the Nurses' Health Study findings. Based on these observations, the authors caution that transgender men undergoing testosterone therapy may face an increased risk of developing glaucoma. Given the complex interplay between male and female sex hormones throughout the lifespan, future investigations should account for these interactions, type and duration of sex hormone use, and well-established female-specific risk factors, such as age at menopause.

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