Hormonal Modulation of Keratoconus: A Systematic Review and Screening Strategy for At-Risk Populations

Area of Science:

• Ophthalmology
• Endocrinology
• Genetics

Background:

• Keratoconus (KCN) is a progressive corneal disease with unclear causes.
• Current screening methods for KCN are insufficient for at-risk individuals.
• Fluctuations in hypothalamic-pituitary-gonadal (HPG) axis hormones may represent a risk factor for KCN.

Purpose of the Study:

• To systematically review the association between HPG axis hormonal fluctuations and KCN.
• To evaluate the role of hormonal changes in KCN development and progression.
• To inform enhanced screening and management strategies for KCN.

Main Methods:

• Comprehensive literature search across major databases (PubMed, Scopus, Web of Science, Embase, Google Scholar) up to July 2025.
• Inclusion of studies with clinical evidence linking HPG axis hormones to KCN onset or progression.
• Data extraction and quality assessment using PRISMA and Joanna Briggs Institute (JBI) tools.

Main Results:

• Twenty-six studies (4201 participants) were included.
• Endogenous (pregnancy, congenital abnormalities) and exogenous (hormone therapy) hormonal shifts were implicated.
• Eight of ten case-control studies showed significant alterations in sex steroids (e.g., DHEAS, estradiol) and gonadotropins in KCN patients.

Conclusions:

• Consistent associations exist between HPG axis hormone fluctuations and KCN.
• Altered DHEAS, estrogens, and gonadotropins are key hormones linked to KCN.
• Hormonal influences are significant in KCN etiology, management, and screening, especially during hormonal shifts.