Abstract
BACKGROUND: Keratoconus (KC) is a progressive bilateral corneal ectatic disorder characterized by corneal thinning, irregular astigmatism, and subsequent vision impairment. The main purpose of this study is to investigate sex hormone-mediated variations in corneal morphology and biomechanics among KC patients, with stratification by age, gender, and menstrual phase. METHODS: This cross-sectional study enrolled 435 participants (KC: n = 180; control: n = 255). Serum testosterone (T), estradiol (E(2)), and progesterone levels were measured using chemiluminescent immunoassay. Serum sex hormones and corneal morphological and biomechanical parameters were analyzed across three age groups (≤ 20, 21–30, > 30 years) and menstrual phases (follicular, luteal, and ovulatory phase). Statistical analyses included Mann-Whitney U tests and Spearman correlations. RESULTS: Male KC patients exhibited significantly lower E(2) (95.23 ± 27.80 vs. 110.60 ± 28.25 pmol/L; P < 0.001) and T (11.73 ± 4.17 vs. 13.17 ± 4.57 nmol/L; P = 0.013) versus controls. While, females KC patients showed significantly lower T (0.84 ± 0.34 vs. 0.96 ± 0.54 nmol/L; P = 0.041) versus controls. E(2) levels were significantly lower in the male KC group compared to the male control group across all age groups (P < 0.017). T levels between the KC and control groups differed most markedly in the 21–30 years group (P = 0.031). Biomechanically, E(2) levels were negatively correlated with Belin/Ambrosio enhanced ectasia total deviation index and Integrated Radius both in the ≤ 20 and > 30 years group in males. T levels were significantly lower in KC female patients aged 21–30 years during the luteal phase compared to controls; however, no significant correlation was found between T levels and any of the measured corneal parameters. CONCLUSION: The associations between sex hormones and KC progression varied depending on the specific hormone and sex. In males, higher E(2) and T levels were associated with more favorable corneal biomechanical and morphological outcomes. Our data identified the 21–30-year age period as exhibiting the most pronounced associations between sex hormones and corneal parameters. These findings highlight the necessity for longitudinal and interventional studies to clarify any causal role of sex hormones in KC progression and their potential therapeutic relevance.