Sex Hormones, Ocular Surface Sensitivity and Dry Eye Symptoms and Signs in Postmenopausal Women

Abstract

Sex hormones may influence symptoms and signs of dry eye. This thesis aims to identify relationships between circulating sex hormones and dry eye symptoms and signs and to investigate the effects of transdermal sex hormones treatment on these variables. Method development was undertaken for ocular surface sensitivity and the Cochet-Bonnet aesthesiometer was selected above a pneumatic instrument based on validation and repeatability data. A cross-sectional study of 76 normal-to-mild dry eye subjects demonstrated inverse relationships between circulating androgens, their precursors or metabolites and symptoms (r = -0.34, p = 0.003) and tear osmolarity (r = -0.30,p = 0.03) and positive associations with corneal sensitivity (r = 0.28, p = 0.02) and tear volume (r = 0.35, p = 0.002). In contrast, oestradiol was positively associated with symptoms (r = 0.31, p = 0.03) in women only. However, when potential confounding was considered, neither androgen nor oestradiol were able to predict symptoms in regression analysis. A similar analysis in 45 postmenopausal women with dry eye, showed that oestradiol was positively associated with corneal staining (r = 0.56, p = 0.001), but there were no relationships between symptoms and hormone levels in either univariate or multivariable analysis. A double-masked randomised placebo-controlled 8 week pilot intervention study was conducted on 40 postmenopausal women with dry eye using transdermal testosterone, oestradiol or their combination. Key findings included a significant improvement in ocular symptoms in the testosterone, combination and placebo groups (p < 0.1) and increased in tear volume in the combination group (p < 0.05). While dry eye signs and symptoms in a mild dry eye population show associations with hormones, specifically an improvement with androgen and the reverse with oestradiol, these relationships were not evident in multivariable analyses. Corneal staining was associated with oestradiol in postmenopausal women with dry eye and an intervention study suggested that a combination of testosterone and oestradiol improved both the signs and symptoms of dry eye in this group. This thesis describes a series of studies to establish the influence of hormones on dry eye signs and symptoms in males, menstruating and postmenopausal women. Such relationships are likely to vary with hormone levels, the combination of key hormones and dry eye status. The inferior conjunctival sensitivity was among the significant predictors of symptoms, revealing the importance of ocular surface sensitivity as an important dry eye clinical indicator. The corneal sensitivity measurement may be affected by the androgen level especially in males.