A study recently presented at The Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting evaluated potential sex-differences in glaucoma risk, including age of menopause as a potential risk factor.
Give me some background.
A growing body of literature has pointed to menopause as a potential sex-specific risk factor for glaucoma in women.
In fact: As we previously reported, a 2024 retrospective study found that longer duration of estrogen hormone therapy use was associated with a later diagnosis of glaucoma in postmenopausal women.
- Meaning: Estrogen supplementation may directly influence the pathophysiological processes involved in glaucoma development and progression.
Now, talk about the study.
Investigators compared peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured by optical coherence tomography (OCT) among healthy adults (n = 6,133 [11,585 eyes]).
- In addition: They evaluated whether the age at menopause was associated with RNFL thickness among women.
Who made up the study cohort?
Data was collected from participants aged 50+ from three population-based studies of individuals of self-described African, Chinese, or Latin American ancestry.
Analyses were adjusted for the following parameters to assess potential confounding factors:
- Disc area
- Scan signal strength
- Axial length (AL)
- Age
- Systolic / diastolic blood pressure
- Hemoglobin A1C (HbA1c) levels
Findings?
Males exhibited significantly thinner average RNFL thickness compared to females (P < 0.001), a difference that persisted after adjusting for potential confounders.
- Note: This sex-difference was consistent across the African, Chinese, and Latin American groups.
In terms of quadrant-specific RNFL measurements, significant sex differences were observed in the inferior and temporal quadrants (P < 0.001)—but not in the superior or nasal quadrants (P > 0.05):
- Inferior quadrant female-male difference: 2.9 μm (123.3 vs. 120.4 μm)
- Temporal quadrant female-male difference: 1.7 μm (64.8 vs. 63.1 μm)
Note: The 2.9 μm and 1.7 μm sex differences were equivalent to men having increased age-related RNFL loss by 6 and 20 years, respectively, compared to women of the same age.
How did menopause affect RNFL thickness?
A dose-dependent relationship between age at menopause and RNFL thickness in the inferior quadrant was observed wherein later age at menopause correlated with thicker RNFL (p = 0.046).
The age at menopause impacted the average RNFL thickness as follows:
- Menopause after age 50: 122.5 μm
- Menopause between ages 45-49: 121.8 μm
- Menopause before age 45: 121.0 μm
Take home.
These results suggest that estrogen may play a protective role against neurodegeneration in the optic nerve—potentially contributing to a lower risk of glaucoma among women.
As such: Clinicians may benefit from considering sex and hormonal factors for glaucoma risk assessments and interventions to provide optimal care.