Keratoconus (KCN) remains a frustratingly unpredictable corneal ectasia: often progressive, frequently diagnosed late, and still lacking universally accepted screening strategies for those most at risk. While eye rubbing, atopy, and genetic predisposition dominate most clinical conversations, a new systematic review argues that another factor deserves far more attention in everyday practice: hormonal fluctuation.
In Ophthalmology Science, researchers from the US and Iran present a PRISMA (Preferred Reporting for Systematic Reviews and Meta-Analyses)-guided systematic review exploring the relationship between hypothalamic–pituitary–gonadal (HPG) axis hormones and keratoconus onset or progression, alongside a proposed screening approach for vulnerable groups.
The study authors screened literature spanning more than six decades (January 1963 to July 2025), drawing on data from PubMed, Scopus, Web of Science, Embase and Google Scholar. Eligible studies needed to report clinical KCN development or progression in the context of changes in sex steroids or gonadotropins (including estrogens, progesterone, testosterone, LH/FSH, and GnRH).
Ultimately, 26 studies were included in the review, comprising 16 descriptive observational reports and 10 case–control studies, and representing 4,201 participants. The review spans a broad demographic range, with case–control cohorts including adults from their early twenties through to late fifties.
Across the descriptive studies, most reports linked KCN onset or worsening to identifiable hormonal shifts. Pregnancy emerged as the most common endogenous trigger, with congenital hormonal abnormalities and exogenous hormone exposures (including hormone replacement therapy and anti-androgen treatment) also represented.
In the 10 case–control studies, hormonal differences between KCN and control groups were “consistently reported,” despite varied methodologies and diagnostic criteria being used. The most repeatable finding was elevated DHEAS, reported in all four studies that measured it.
The authors argue that these patterns support a systemic component to KCN risk and progression, and that clinicians should be alert to periods of significant hormonal change as potential windows of vulnerability. “Specifically, altered levels of DHEAS, estrogens and gonadotropins emerged as key hormones linked to KCN pathology,” states the study’s conclusion, “underscoring the importance of hormonal influences in clinical management and screening, particularly during periods of significant hormonal fluctuation, such as pregnancy, congenital endocrine disorders, or hormonal therapy.”
While the evidence remains largely observational, this review strengthens the case for integrating hormonal history into keratoconus risk assessment – and for developing more targeted, proactive screening pathways in real-world clinics.
In Ophthalmology Science, researchers from the US and Iran present a PRISMA (Preferred Reporting for Systematic Reviews and Meta-Analyses)-guided systematic review exploring the relationship between hypothalamic–pituitary–gonadal (HPG) axis hormones and keratoconus onset or progression, alongside a proposed screening approach for vulnerable groups.
The study authors screened literature spanning more than six decades (January 1963 to July 2025), drawing on data from PubMed, Scopus, Web of Science, Embase and Google Scholar. Eligible studies needed to report clinical KCN development or progression in the context of changes in sex steroids or gonadotropins (including estrogens, progesterone, testosterone, LH/FSH, and GnRH).
Ultimately, 26 studies were included in the review, comprising 16 descriptive observational reports and 10 case–control studies, and representing 4,201 participants. The review spans a broad demographic range, with case–control cohorts including adults from their early twenties through to late fifties.
Across the descriptive studies, most reports linked KCN onset or worsening to identifiable hormonal shifts. Pregnancy emerged as the most common endogenous trigger, with congenital hormonal abnormalities and exogenous hormone exposures (including hormone replacement therapy and anti-androgen treatment) also represented.
In the 10 case–control studies, hormonal differences between KCN and control groups were “consistently reported,” despite varied methodologies and diagnostic criteria being used. The most repeatable finding was elevated DHEAS, reported in all four studies that measured it.
The authors argue that these patterns support a systemic component to KCN risk and progression, and that clinicians should be alert to periods of significant hormonal change as potential windows of vulnerability. “Specifically, altered levels of DHEAS, estrogens and gonadotropins emerged as key hormones linked to KCN pathology,” states the study’s conclusion, “underscoring the importance of hormonal influences in clinical management and screening, particularly during periods of significant hormonal fluctuation, such as pregnancy, congenital endocrine disorders, or hormonal therapy.”
While the evidence remains largely observational, this review strengthens the case for integrating hormonal history into keratoconus risk assessment – and for developing more targeted, proactive screening pathways in real-world clinics.
