A middle-aged female presented with exacerbation of her severe dry eye disease (DED). She had been successfully treated with a topical dehydroepiandrosterone (DHEA) androgen crème for mixed aqueous deficient/evaporative dry eye. Unfortunately, the pharmacy discontinued its compounding services. Shortly after discontinuation of topical androgen therapy, her dry eye signs and symptoms began to worsen. During the same time period, a 16-year-old female presented with recent-onset ocular discomfort and intermittently blurred vision. Evaluation revealed significant reduction of her tear film volume and a tear breakup time of five seconds. She showed corneal and conjunctival staining. A few weeks prior to the onset of her issues, her physician had prescribed an estrogen-based oral contraceptive.

These cases demonstrate the considerable impact that sex hormones may exert on the ocular surface. As practitioners, we need understand how we can use sex hormones to enhance ocular surface health.

Androgens are often considered to be “male” hormones and estrogens “female” hormones. In reality, androgens and estrogens are biologically active in both sexes (Truong et al, 2014). For example, early in life, androgens are abundant in both sexes and tend to increase in both boys and girls during puberty.

Less well-known androgens such as dihydrotestosterone (DHT) and androstenedione are important in the development of young males and females. Human androgens such as DHEA and DHEA sulfate (DHEA-S) are secreted by the adrenal glands and are found in peripheral tissues. In males and females, circulating DHEA levels peak between ages 20 to 30 years, thereafter decreasing by age 70 years (Schröder et al, 2016).

Estrogens also play a key role in maintaining the ocular surface. For instance, a higher prevalence of dry eye signs and symptoms among females has been associated with Sjögren’s syndrome, androgen insensitivity syndrome, and polycystic ovary syndrome. This could be due to contraceptives, hormone replacement therapy, and/or ovariectomy. These findings implicate estrogens as a contributor to the development of DED in females (Nichols et al, 2011).

Hormones to Treat Dry Eye?

Sex hormones may be a viable option for treating DED in both sexes. Golebiowski et al (2017) evaluated transdermal testosterone and estrogen as potential therapies for dry eye. After obtaining baseline findings on 40 post-menopausal women, they assigned 10 women to one of four groups. The subjects received one of four transdermal preparations: testosterone, estradiol, testosterone/estradiol combination, or placebo. Each subject rubbed the preparation into the skin of her inner thighs. The results showed increased dryness symptoms in the estrogen group; increased tear secretion in the combination testosterone/estradiol group; and a strong association between increased serum androgen and improved tear stability (Golebiowski et al, 2017).

In another study, O’Connor (2004) described the benefits of topical 3% testosterone crème applied to the eyelids. His findings support the benefits of androgens on dry eye, particularly meibomian gland dysfunction. More than half of the subjects reported significant improvement in dry eye symptoms after using the testosterone cream. While not commercially available, compounding laboratories can prepare this product for patients. CLS

For references, please visit and click on document #279.