The Dry Eye Ménage-a-Trois: Sex, Hormones, and Cosmetics

Though menopause is a natural part of the female aging process, it comes with many unwelcome symptoms – hot flushes, weight gain, joint pain, hair loss, sleep deprivation, and depression, to name a few (1). Lifestyle choices can expedite this process; for example, exposing oneself often to polychlorinated biphenyls (PCBs), phthalates (2), and a myriad of other widely used ingredients in product formulations. It is not well known that various forms of these chemicals are used in personal care products (for example, PCBs can be found in soap and hydrating beauty bars) (3) and cosmetics (for example, phthalates in makeup remover) (4).

The link between menopause and dry eye disease (DED) is even less well-known. Symptoms include ocular irritation, a gritty sensation, redness, secondary epiphora, and visual disturbance. With the cumulative use of eye makeup and skincare that contain one of the following ingredients: parabens (for example, ethylparaben and methylparaben) or essential oils such as tea tree oil (for example, terpinen-4-ol), the process of peri-menopausal DED can be expedited. Parabens abound in many around-eye creams, eyeliners, eyeshadows, glitter, mascaras, moisturizers, and serums, and tea tree oil is a featured ingredient in certain eye makeup removers, eyelash cleansers, moisturizers and toners (4).

How do PCBs, phthalates, parabens, and tea tree oil induce these effects? The answer is that they are all endocrine disruptors (4,5). Endocrine disruptors are natural or human-made chemicals that may mimic, prevent, or interfere with the body’s hormones. Most often these disruptors act as estrogens or anti-androgens and may elicit significant adverse effects (6). Parabens have estrogen potency, tea tree oil and phthalates possess estrogen and antiandrogen activities, and PCBs, depending on their structure, may block or imitate sex steroid actions (4,5).

But, given that menopause and postmenopause are characterized by a loss of estrogen, and androgens are male hormones, why would compounds with estrogen or anti-androgen actions engender a disease like DED in women? One might expect the application of estrogen-like chemicals to help with the restoration of tear film stability and prevent DED, but this is not the case.

Estrogens, and chemicals that act as estrogens, may actually promote the development of DED (7,8), while androgens may prevent DED (7,8).

The major cause of DED is meibomian gland dysfunction (MGD). Meibomian glands (MGs), which are large sebaceous glands situated in the eyelids, secrete an oil (i.e., lipid) and protein mixture that stabilizes and prevents the evaporation of the tear film, and play an essential role in the health and well-being of the ocular surface. Conversely, MGD destabilizes the tear film, increases its evaporation, and is a key trigger for the induction of DED (7,9) (Figure 1).

Estrogens cause a significant decrease in the size, activity, and lipid production of sebaceous glands (7). Indeed, estrogen was once called the prototype agent for the suppression of sebaceous gland activity, and estrogen treatment has been used to decrease sebaceous gland function and secretion in humans (7). Aside from prematurely destroying sebaceous gland cells, mechanisms for this negative estrogen effect include reduced androgen uptake, interference with local androgen synthesis, and antagonism of androgen action (7).

In the MGs estrogen suppresses the transcription of genes involved with lipid generation, mobilization and processing, and significantly reduces the activity of a critical signaling pathway in human MG epithelial cells (7,8). Given these antagonistic effects, as well as the impact of estrogens on sebaceous glands in general, it is most likely that estrogen exposure decreases MG function and promotes both MGD and evaporative DED. Such estrogen action would help answer three conundrums: i) why an epidemiological evaluation of over 25,000 postmenopausal women demonstrated that estrogen replacement therapy significantly increases the signs and symptoms of DED; ii) why an assessment of more than 44,000 women with DED showed that one of the highest prevalences of comorbid conditions was the use of estrogen replacement therapy; and iii) why estrogen treatment of women in several studies led to diminished tear film breakup time (the time taken for the tear film to destabilize), foreign body sensation, contact lens intolerance and ocular surface dryness (7). In effect, chemicals that act like estrogens do not appear ideal for eyelid MGs or for the tear film.

In contrast, androgens stimulate MG function, improve the quality and/or quantity of lipids produced by this tissue and enhance the formation of the tear film’s lipid layer. Androgen deficiency, in turn, will lead to MGD, tear film instability and evaporative DED (7,8). Consequently, endocrine disrupting ingredients in eye makeup, which have anti-androgen activities, will promote the development of DED.

Why are anti-androgens a problem for women? Androgens are very important hormones for women and are critical for reproductive ability, cardiac health, bone metabolism, muscle structure, and brain function (10). Human females produce an amount of androgens equivalent to over two-thirds of the androgens made by men (7,8). A woman's androgen production decreases progressively from the age of 30 years, leading to an androgen deficiency by post-menopause. This androgen loss may well be a significant reason for why the prevalence of DED is so high in post-menopausal women (7,8). Women have twice the risk of developing DED compared to men and the combination of lower androgen levels and endocrine disrupting makeup ingredients are likely to be a significant contributor (8).

Phthalates, parabens, and tea tree oil are not the only endocrine disrupting culprits in eye makeup. Soy ingredients, such as isoflavones, are phytestrogens and also act as endocrine disruptors (11). Additional endocrine disruptors in eye makeup include benzophenone, butylated hydroxyanisole, butylated hydroxytoluene, cyclopentasiloxane (cyclomethicone), per- and poly-fluoroalkyl substances, siloxane D4, thimerosal and triclosan (4) (Figure 2:)

Overall, endocrine disruptors can be harmful to our health. They are linked not only to DED but also to reproductive disorders, obesity, diabetes, cancers, neurological problems, immune and thyroid disorders and osteoporosis (12).

The eye care professional can significantly influence the onset and prevention of DED in their female patients. Encourage ingredient checking with apps and websites such as www.incidecoder.com, discourage the use of recognized endocrine disruptors, and counsel their menopausal patients who are on estrogen replacement therapy.