Gonadal Hormones and Retinal Disorders: A Review

Abstract

Aim: Gonadal hormones are essential for reproductive function, but can act on neural and other organ systems, and are probably the cause of the large majority of known sex differences in function and disease. The aim of this review is to provide evidence for this hypothesis in relation to eye disorders and to retinopathies in particular.

Methods: Epidemiological studies and research articles were reviewed.

Results: Analysis of the biological basis for a relationship between eye diseases and hormones showed that estrogen, androgen, and progesterone receptors are present throughout the eye and that these steroids are locally produced in ocular tissues. Sex hormones can have a neuroprotective action on the retina and modulate ocular blood flow. There are differences between the male and the female retina; moreover, sex hormones can influence the development (or not) of certain disorders. For example, exposure to endogenous estrogens, depending on age at menarche and menopause and number of pregnancies, and exposure to exogenous estrogens, as in hormone replacement therapy and use of oral contraceptives, appear to protect against age-related macular degeneration (both drusenoid and neurovascular types), whereas exogenous testosterone therapy is a risk factor for central serous chorioretinopathy. Macular hole is more common among women than men, particularly in postmenopausal women probably owing to the sudden drop in estrogen production in later middle age. Progestin therapy appears to ameliorate the course of retinitis pigmentosa. Diabetic retinopathy, a complication of diabetes, may be more common among men than women.

Conclusion: We observed a correlation between many retinopathies and sex, probably as a result of the protective effect some gonadal hormones may exert against the development of certain disorders. This may have ramifications for the use of hormone therapy in the treatment of eye disease and of retinal disorders in particular.

Keywords: age-related macular degeneration; estrogens; eye disorders; gonadal hormones; hormone therapy; optic nerve; retinopathies; sex-related differences.

Figure 1

Neurosteroid synthesis in the retina. The drawing report of the metabolic pathway leading to estradiol synthesis within the retina (11, 14). The steroidogenic enzymes already identified for their mRNA, activity or immunolocalization are indicated within yellow boxes. The enzymes still lacking of identification are indicated within the grey boxes. Dotted lines indicate so far unclear enzymatic activities. Abbreviations: 3β-HSD, 3β-hydroxysteroid dehydrogenase; 3α-HSD, 3α-hydroxysteroid dehydrogenase; 5αDH-DOC, 5 alpha-dihydrodeoxycorticosterone; 5αDHP, 5α-dihydroprogesterone; 5α-R, 5α-Reductase; 17β-HSD1, 17β-hydroxysteroid dehydrogenases 1; 17β-HSD4, 17β-hydroxysteroid dehydrogenases 4; 17β-HSD5, 17β-hydroxysteroid dehydrogenases 5; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; DOC, deoxycorticosterone; HMG-CoA, hydroxymethylglutaryl-CoA; HMGCoA-R, hydroxymethylglutaryl-CoA reductase.