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BLOG: How do androgen and estrogen affect dry eye?
I work in the optometry clinic at a VA hospital, so I see a lot of men older than 65 years, and the vast majority of my patients have meibomian gland dysfunction.
Some of them complain about the typical dry eye symptoms and some of them don’t, but I’ve always felt a little helpless about dry eye complaints in the older population. It seems I can make their symptoms better – or tolerable – but nothing I do really changes their gland anatomy.
From a slit lamp exam, the meibomian glands continue to atrophy as the patient gets older. And it’s easy to just attribute this finding as a part of the aging process, but for this article, I wanted to get deeper into why the meibomian glands tend to wither away as we age. And my research led me to sex.
Sex hormones, specifically. There is increasing evidence that changes in levels of sex hormones can disrupt the homeostasis of our lacrimal system and cause dry eye symptoms. We’ll get to how they do that in a bit but, first, a refresher.
The main types of sex hormones are androgens, estrogens and progestogens. They are steroid hormones and are secreted by the gonads (ovaries and testes) and the adrenal glands. Each type of sex hormone is found in males and females, it’s just that females have much more estrogen and progestogen than males, and males have much more androgen than females (testosterone is a type of androgen). There are sex hormone receptors in our conjunctival goblet cells, lacrimal glands and meibomian glands, all of the sites where the components of the tear film are made.
Meibomian glands. The meibomian gland is essentially a large sebaceous gland and, therefore, its secretions are susceptible to changes in body chemistry. Androgens enhance sebaceous gland function, while estrogens and progestogens suppress function. There is much evidence that shows increasing androgen levels in mammals causes an increase in the quality and quantity of meibum secreted. There is also evidence showing that low androgenic activity results in meibomian gland dysfunction (MGD) and compromised secretions. This last fact is shown in individuals who do not respond to androgens due to androgen receptor antagonists. Women with complete androgen insensitivity syndrome and men using anti-androgen therapy for prostate cancer show signs of ocular surface disease and MGD more than their counterparts.
Androgens also help to suppress genes that cause keratinization, which is the primary mechanism of MGD. As we age, androgen levels markedly decrease and, by the time patients in each gender are 50 years, androgen is at about 30% of peak levels. Estrogens and progestogens are a little more complicated and don’t act directly on the meibomian gland, but antagonize the action of androgens and attenuate testosterone uptake.
Lacrimal glands. Like the meibomian glands, androgens have a positive correlation with lacrimal gland function. A reduction in androgen influence, like what happens in Sjögren’s syndrome, results in inflammatory changes in the lacrimal gland and, subsequently, aqueous-deficient dry eye. The effect of estrogens and progestogens on the lacrimal gland is mixed in the literature, and further research is needed.
Conjunctival goblet cells. The goblet cells secrete the mucin layer of the tear film, responsible for stabilizing the tear film, decreasing the surface tension and allowing it to better spread around the ocular surface. Based on studies of women with androgen insensitivity, we know that androgens play a role in increasing the production of mucin by goblet cells. Interestingly, it seems that for goblet cells, estrogens and progestogens may also have a positive effect on increasing the mucin layer of the tear film, although the complete effect remains to be fully determined.
I think it’s important that we primary eye care providers understand that sex hormone levels can have a profound impact on dry eye symptoms. It would seem that one of the reasons I see so much atrophy of meibomian glands in my patient base is because falling androgen levels are allowing fibrosis of the glands themselves. But dry eye is multifactorial, and certainly an inflammatory condition, and sex hormones have a large effect on the immune system.
Next month we’ll talk a little bit more about the inflammatory changes that happen in sex hormone-related dry eye, and we’ll get into the treatment being advocated for these patients.
References:
Ding J, et al. Exp Gerontol. 2012;47:483-490. doi:10.1016/j.exger.2012.03.020.
Tomlinson A, et al. Invest Ophthalmol Vis Sci. 2011;52:2006-2049. doi:10.1167/iovs.10-6997f.
Truong S, et al. Clin Exp Optom. 2014;97:324-336. doi:10.1111/cxo.12147.
Stanczyk FZ, et al. J Steroid Biochem Mol Biol. 20. 2013;138:10-16. doi:10.1016/j.jsbmb.2013.02.015.
Sullivan DA, et al. Ann N Y Acad Sci. 2002;966:211-222.
Suzuki T, et al. Ann N Y Acad Sci 2002;966:223-225.