Dry Eye Corner Part 7

Figure 1. Hormones play a central role in maintaining ocular surface health

In Dry Eye Corner Part 7, Keith Tempany explores the role of hormones and gender in dry eye disease…

As we all know, dry eye disease (DED) is a multifactorial condition that affects millions of people worldwide, with a striking and well-documented difference in prevalence between sexes*.

Evidence consistently shows that the female sex is a significant risk factor for the development of DED, highlighting the importance of biological sex as a major risk factor in the development of DED¹.

Sex differences in dry eye disease

The higher prevalence of DED in females reflects broader biological patterns. It should, therefore, come as no surprise that such sex related variation exists in the prevalence of an eye disease – or indeed in any aspect of ocular function – given that differences related to sex are evident across almost every cell, tissue, and organ system in the body.

In fact, since 1945, more than 575,000 scientific reports have been published examining the fundamental and/or clinical impact of sex on human physiology and pathophysiology¹.

In the eye, these differences are particularly pronounced. Variations in structure, function, and disease susceptibility have been documented, with many of these differences linked directly to hormonal influences².

Hormonal regulation of the ocular surface

Hormones play a central role in maintaining ocular surface health (Figure 1). A wide range of hormonal systems are involved, including:

• Sex steroids such as androgens and oestrogens
• Hypothalamic-pituitary hormones
• Glucocorticoids
• Insulin and insulin-like growth factor one
• Thyroid hormones

These hormones contribute to the regulation of tear production, ocular surface integrity, and the function of associated structures such as the lacrimal and meibomian glands.

For example, androgens are extremely important in the regulation of the ocular surface and adnexa, they appear to mediate many of the sex related differences in these tissues.

However, androgen deficiency impairs lacrimal gland function, creates a risk for meibomian gland dysfunction (MGD), and is linked to the development of both aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE).

In contrast to androgens, the role of oestrogens at the ocular surface is more complex and less clearly defined with effects that appear to be dependent on biological sex, tissue type, and hormone dose².

Distinguishing sex and gender in dry eye disease

It is essential to distinguish between ‘sex’ and ‘gender’ when considering DED:

• Sex refers to biological classification based on chromosomes and reproductive anatomy
• Gender refers to socially constructed roles, behaviours, and identities (as stated in a 2001 report from the US Institute of Medicine (US)3

While biological sex influences hormonal regulation and disease mechanisms, gender can affect:

• Health perceptions
• Access to care
• Treatment-seeking behaviours
• Interactions with healthcare systems

Both factors are intertwined and contribute to health outcomes and disparities in DED1.

Sex steroid hormones are known to have a role in the pathogenesis of multiple ocular diseases. In a small study looking at ocular findings in transgender patients undergoing hormonal therapy, 40 per cent of the male to female (MTF) patients presented with or had a history of ‘dry eye syndrome’⁴.

In contrast, none of the female to male (FTM) patients had signs or symptoms of dry eyes. Moreover, hormone therapy in all four affected patients consisted of oestrogen and an anti-androgen. Therefore, the concurrent increase in oestrogen and suppression of testosterone may have predisposed MTF patients to DED⁵.

Providing effective healthcare for transgender and gender-diverse individuals can be challenging, largely due to gaps in specialised knowledge alongside social and cultural barriers. Addressing these issues requires further clinical research and improved education for healthcare professionals⁶.

Hormones, health disparities and patient experience

The interplay between hormones, sex and gender extends beyond biological mechanisms to influence broader aspects of disease:

• Risk and prevalence of DED
• Clinical presentation
• Immune responses
• Pain perception
• Care seeking behaviours and utilisation¹

Figure 2

Dry eye disease and perimenopause and menopause

Although, anecdotally, the menopause has been regarded as a major risk factor for DED, the TFOS DEWS reports indicate that menopause is not considered a direct or isolated cause of DED, highlighting instead a complex interplay involving androgen deficiency and systemic comorbidities⁷.

Current understanding emphasises that hormonal shifts and changes in receptor sensitivity, rather than menopause alone, drive ocular surface changes and MGD⁷.

As the body’s production of oestrogen, androgen and progesterone decreases during the phases of menopause, initially oestrogen doesn’t drop dramatically but tends to oscillate before resulting in a permanent reduction (Figure 2).

Changing levels of different hormones will have different influences on factors contributing to the exacerbation or relief of DED. For instance, reduced oestrogen levels may enhance lipid secretion from the meibomian glands while simultaneously diminishing goblet cell mucin production.

It has been documented that oestrogen can relieve symptoms early on, yet it can lead to adverse effects in later stages⁸. Consequently, menopausal hormone therapy (MHT) may exert both beneficial and adverse effects in patients with dry eye disease.

Interestingly, a study of 25,000 postmenopausal women using oestrogen only MHT presented with a greater risk of DED⁹.

The eyecare practitioner’s role

Hormones play a fundamental role in the development and progression of DED. The higher prevalence of DED in women underscores the importance of hormonal influences – particularly the protective role of androgens and the less clearly defined effects of oestrogens.

There is clearly more research to be done and obviously there is no ‘one size fits all’ guidebook as to what to do and when with this complex subject. Maintaining the patient at the centre of your decision-making is always key, but asking about your patients’ menopause status, age of menopause onset and use of MHT could be useful during history and symptoms.

As we’ve discussed, MHT comes in different formulations and modes of delivery, so looking up each particular MHT might help us to understand the potential effects on our patients’ bodies and their eyes.

Overall, the relationship between hormones and DED exemplifies the broader importance of considering both biological sex and gender in modern healthcare.

References

1. Craig JP et al. TFOS DEWS II Report Executive Summary. The Ocular Surface 2017;15(4):802-812.
2. Sullivan D A et al. TFOS DEWS II Sex, Gender, an Hormones Report. The Ocular Surface 2017;15(3):284-333.
3. Wizemann TM and Pardue ML Eds. Exploring the biological contributions to human health: does sex matter? Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences. Washington DC: The National Academies Press (US) 2001.
4. Nuzzi R and Caselgrandi P. Sex hormones and their effects on ocular disorders and pathophysiology: current aspects and our experience. Int. J. Mol. Sci. 2022;23(6):3269.
5. Nieves-Ríos C et al. Instances of ocular findings in transgender patients undergoing hormonal therapy. Am. J. Ophthalmol. Case Rep. 2023;28:32.
6. Stapleton F et al. TFOS DEWS III Digest. Am. J. Ophthalmol. 2025;279:451-553.
7. Wolffsohn J et al. TFOS DEWS III: Diagnostic Methodology. Am. J. Ophthalmol. 2025;279:387-450.
8. Sherwin BB. Estrogen and cognitive aging in women. Neuroscience 2006;138(3):1021-6.
9. Schaumberg D et al. Hormone replacement therapy and dry eye syndrome. JAMA 2001;286(17):2114-9.

* It’s important to understand why the word ‘sex’ is used in this article. While people often treat ‘sex’ and ‘gender’ as if they mean the same thing, they’re actually quite different. According to a 2001 Institute of Medicine report3, ‘sex’ describes the classification of living beings – typically male or female – based on reproductive organs and chromosomal make-up.

On the other hand, ‘gender’ is about how individuals present themselves as men or women, or how society reacts to their gender expression. Although gender has biological roots, it is influenced by environment and personal experience. Put simply, sex defines males and females through biological traits, whereas gender encompasses socially constructed behaviours and expectations associated with being masculine or feminine. Moreover, gender is not fixed; it’s shaped by context and exists along a spectrum.

Keith Tempany FBDO CL FBCLA qualified in 1976 and worked in both independent and multiple practice before opening a fee-based contact lens only practice in 2002. He is a fellow and a past president of the British Contact Lens Association (BCLA) and oversaw the development and launch of its Myopia Management Certificate. Keith is the store director of Leightons & Tempany Opticians & Hearing Care in Poole, and works as an independent consultant. He is an experienced author, lecturer and facilitator of contact lens and dry eye education both nationally and internationally.