# Sex Hormones and Keratoconus: In Search of the Link

**Authors:** Iasonas Makrypoulias, Irini Chatziralli, Dimitris Papaconstantinou, Konstantinos Panagiotopoulos, Stylianos A. Kandarakis, Petros Petrou, Anke Messerschmidt-Roth, Konstantinos Droutsas

PMC · DOI: 10.3390/jcm15041528 · 2026-02-14

## TL;DR

This study explores the link between sex hormones and keratoconus, finding hormonal correlations with corneal changes and treatment outcomes.

## Contribution

The study identifies specific hormonal associations with keratoconus progression and treatment in a Greek population.

## Key findings

- LH correlated positively with corneal biomechanical parameters.
- FSH levels were higher in patients who underwent penetrating keratoplasty.
- Hormonal differences were observed between men and women with keratoconus.

## Abstract

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.

## Linked entities

- **Chemicals:** follicle-stimulating hormone (PubChem CID 62819), estradiol (PubChem CID 450), prolactin (PubChem CID 168266256), testosterone (PubChem CID 6013), dehydroepiandrosterone sulfate (PubChem CID 12594), progesterone (PubChem CID 5994)
- **Diseases:** keratoconus (MONDO:0015486)

## Full-text entities

- **Genes:** SRGN (serglycin) [NCBI Gene 5552] {aka PPG, PRG, PRG1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TES (testin LIM domain protein) [NCBI Gene 26136] {aka TESS, TESS-2}, PIP (prolactin induced protein) [NCBI Gene 5304] {aka BRST-2, GCDFP-15, GCDFP15, GPIP4}
- **Diseases:** Thyroid gland disorders (MESH:D013959), irregular astigmatism (MESH:D001251), CCT (MESH:C535338), eye disease (MESH:D005128), corneal alterations (MESH:D065306), cryptorchidism (MESH:D003456), Inflammation (MESH:D007249), PK (MESH:D015807), ectatic disease (MESH:D004194), injury to (MESH:D014947), CH (MESH:D003316), visual impairment (MESH:D014786), HC (MESH:D000067329), corneal ectasia (MESH:D004108), corneal dystrophies (MESH:D003317), CRF (MESH:D060467), metabolic insufficiency (MESH:D000309), KC (MESH:D007640), dry eye syndrome (MESH:D015352), myopia (MESH:D009216)
- **Chemicals:** estrone (MESH:D004970), ATP (MESH:D000255), TES (MESH:D013739), DHEAS (MESH:D003687), LH (MESH:D007986), PRG (MESH:D011374), E1,E3 (-), ABEI (MESH:C031912), zinc (MESH:D015032), E2 (MESH:D004958), DHEA-S (MESH:D019314)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12941997