Purpose

Previous studies suggest that hormone therapy favorably affects intraocular pressure (IOP). Here, we examined the association between hormone therapy use and IOP in the context of a large randomized trial.

Design

Secondary data analysis from a randomized controlled trial.

Methods

We used data from the Women's Health Initiative-Sight Exam (WHISE). Women with prior hysterectomy received oral conjugated equine estrogen (0.625 mg/day) or placebo. Women with a uterus received estrogen plus progestin (medroxyprogesterone acetate 2.5 mg/day) or placebo. IOP was measured 5 years after randomization. Adjusted linear regression models were used to assess the association between hormone therapy and IOP.

Results

The WHISE included 1668 women in the estrogen-alone trial (aged 63-86, mean 72 years) and 2679 women in the estrogen-plus-progestin trial (aged 63-87, mean 72 years). In multivariate analyses, compared to placebo treatment, treatment with estrogen alone was associated with a 0.5 mm Hg reduction of the IOP in the right eye (95% CI: -0.8, -0.1, P = .005) and a 0.6 mm Hg (95% CI: -0.9, -0.3, P < .001) reduction of the IOP in the left eye. In the estrogen-plus-progestin trial, there was no significant difference in IOP between the treatment and placebo groups (P = .30 right eye and P = .43 left eye).

Conclusions

This study represents an IOP analysis in the largest hormone trial available. Estrogen-alone therapy in postmenopausal women is associated with a small but significant IOP reduction of 0.5 mm Hg. The clinical significance of this small decrease remains to be determined.

Purpose:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.