Potential Treatments for Postmenopausal Dry Eye

The prevalence of postmenopausal dry eye disease (DED) is high—DED is 50% more prevalent among females than males, and up to 72% of these women are postmenopausal.^1,2

This column discusses potential treatments in the pipeline that aim to effectively treat DED in this patient population.

HORMONE REPLACEMENT THERAPY (HRT)

This therapy is designed to regulate and replace the hormones the body produces less of during menopause, most commonly estrogen. It is prescribed for women who experience significant symptoms, such as hot flashes, sleep disturbances, night sweats, mood changes, vaginal dryness, and decreased libido, all resulting from menopause and most common in those who have had a hysterectomy.^3,4 A hysterectomy may involve removing only the ovaries or removing both the ovaries and the uterus. If the patient had both their ovaries and their uterus removed, they will take estrogen-only HRT. This is because there is no uterus present, so the patient will not have any risk associated with estrogen-induced endometrial cancer.^3,4 Those who retain a uterus will usually receive combined estrogen and progesterone HRT to protect the uterine endometrium.⁵

HRT is controversial, as it has shown mixed results. A review of seven randomized, controlled HRT studies shows increased Schirmer scores, but no significant effect on DED symptoms or tear breakup time (TBUT).⁶ On the other hand, a different study revealed the combination of estrogen and progesterone in 40 postmenopausal women worsened DED symptoms in about one-third of participants by month 3 of treatment.⁷ Additionally, systemically, oral estrogen has been associated with an increased risk of breast cancer, stroke, deep vein thrombosis, and pulmonary embolisms.^4,5

TRANSDERMAL AND TOPICAL THERAPY

Sex hormones, specifically androgens, have been found to be a key regulator of meibomian gland function. There are multiple clinical studies on transdermal eyelid therapy and topical eye drops in postmenopausal women that show improved TBUT, aqueous secretion, Schirmer scores, and Ocular Surface Disease Index scores.^8-17 These therapies are believed to stimulate androgen receptors on the meibomian glands, lacrimal gland, cornea, and conjunctiva.⁷ Ideal candidates have endogenous androgen deficiencies with meibomian gland keratinization and/or atrophy.^18,19

SYSTEMIC HORMONE THERAPY

Currently, there is little evidence to suggest oral systemic therapies are efficacious in the management of DED. Dehydroepiandrosterone (DHEA) has been extensively investigated in autoimmune patients who have DED. A randomized double-blind study evaluated 28 Sjögren syndrome patients using 200 mg of oral DHEA daily over 24 weeks.²⁰ Of note, these patients were androgen-deficient primarily from hypothalamic-pituitary-adrenal axis dysfunction. At the conclusion of the study, no significant change in symptoms, corneal fluorescein staining, or Schirmer scores was reported.

Currently, there are no FDA-approved testosterone topical drops approved for DED. However, physicians can prescribe compounded testosterone eye drops, gels, or ointments through specialty compounding pharmacies for off-label use. One study found that applying 4.5% testosterone gel on the upper and lower lid margins improved meibum quality, TBUT, and ocular symptoms.³

CLINICAL BARRIERS

There is potential promise in using HRT to alleviate DED. However, oral versus topical therapy use remains elusive due to a lack of studies conducted in this area. Additionally, the systemic effects associated with androgen-based treatments and their unclear long-term safety profiles remain problematic. These uncertainties contribute to the limited adoption of androgen-based treatments for DED. With further research, practitioners may be able to incorporate androgen-based therapies into their treatment algorithm where appropriate to manage postmenopausal DED with a more targeted, effective approach.