Sex Hormones and Keratoconus: In Search of the Link

Background: Keratoconus (KC) is the most common ectatic corneal disorder, causing progressive corneal deformation, visual impairment, and reduced quality of life. Although KC pathogenesis is multifactorial, the contribution of systemic factors, including hormonal regulation, remains incompletely understood. This study aimed to investigate the role of sex hormones and gonadotropins in KC in a predominantly Greek population. Methods: We recruited 105 KC patients and 71 healthy controls (HC). Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), testosterone (TES), dehydroepiandrosterone sulfate (DHEA-S), and progesterone (PRG) were measured and analyzed in relation to corneal tomographic and biomechanical parameters, as well as treatment modality. Results: LH showed positive correlations with corneal biomechanical parameters. KC patients who underwent penetrating keratoplasty exhibited higher FSH levels and a reduced LH/FSH ratio compared with those treated with corneal cross-linking. E2 levels were increased in women over 46 years of age, while PRL correlated with Kmax and Q-value. Men with KC demonstrated reduced TES associated with corneal morphology and biomechanics, increased PRG levels, and reduced DHEA-S in keratoplasty-treated patients. Conclusions: These findings suggest that sex hormones and gonadotropins may contribute to KC pathophysiology, supporting a systemic hormonal component in disease progression.