Keratoconus is usually framed as a disease of genetics, eye rubbing, inflammation, and corneal biomechanics. But a new study suggests another factor may deserve closer attention: sex hormone imbalance.
In a paper published in Investigative Ophthalmology & Visual Science, researchers from Tianjin Medical University Eye Hospital, China, investigated whether estradiol and testosterone influence corneal collagen metabolism and biomechanical stability in keratoconus. Their findings point to elevated estrogen as a potential upstream driver of stromal remodeling, collagen degradation, and corneal weakening.
The clinical arm of the study enrolled 15 newly diagnosed, treatment-naïve keratoconus patients and 12 age- and sex-matched controls. Plasma and tear levels of estradiol, testosterone, and matrix metalloproteinase-2 (MMP2) were measured by ELISA (enzyme-linked immunosorbent assay). The researchers found that keratoconus patients had significantly higher estradiol levels in both plasma and tears, while testosterone levels were unchanged. Tear MMP2 was also elevated.
Importantly, tear estradiol correlated with several markers of disease severity. Higher tear estradiol was associated with steeper mean keratometry, greater refractive error, thinner minimum corneal thickness, worse best-corrected visual acuity, and higher MMP2 levels. When the authors stratified by sex, these associations appeared to be driven mainly by male keratoconus patients; no significant differences or correlations were detected in the small female subgroup.
The study does have its limitations. For example, the clinical cohort was small, particularly for sex-stratified analysis, and menstrual-cycle timing was not available for female participants. But still, the findings do offer a coherent mechanistic story: elevated estrogen may promote keratoconus progression by increasing MMP-driven collagen degradation and weakening stromal architecture.
For clinicians, the study could help to explain why the disease often emerges during adolescence and why progression can be influenced by pregnancy or hormone therapy. It also adds sex hormone–responsive matrix remodeling to the expanding keratoconus pathophysiology framework, raising the possibility of new therapeutic targets beyond mechanical stabilization alone.
