Exploring the groundbreaking research connecting hormonal balance to ocular surface health
Imagine feeling like you have sand in your eyes every time you blink. For millions of people worldwide, this isn't just an occasional discomfort—it's a daily reality. Dry eye disease (DED) is a common condition that causes ocular discomfort, visual disturbances, and potential damage to the ocular surface. But here's what's particularly striking: women suffer from dry eye two to four times more frequently than men 3 .
This significant gender disparity has led scientists on a quest to understand why, and the trail has led directly to our hormones.
The connection goes beyond simple biology. From puberty through pregnancy to menopause, women experience constant hormonal fluctuations that appear to have profound effects on their eye health. Recent research has begun to unravel this complex relationship, revealing how hormones like androgens, estrogens, and progesterone influence the very structures that keep our eyes comfortable and well-lubricated 1 .
Women experience dry eye more frequently than men
Sex hormones directly impact ocular surface health
New studies reveal complex hormone-eye connections
To comprehend how hormones affect dry eye, we must first understand what specialists call the "ocular surface system." This integrated system includes the cornea, conjunctiva, tear film, lacrimal glands, meibomian glands, eyelids, and the neural connections that link them all together 3 .
Androgens, including testosterone, play a remarkably beneficial role in maintaining ocular surface health. These hormones exert trophic effects on both meibomian and lacrimal glands, supporting their structure and function 1 .
The meibomian glands express enzymes that convert testosterone to its more potent form, dihydrotestosterone (DHT), and androgens stimulate genes involved in lipid production and secretion 1 3 .
The effects of estrogen and progesterone on the ocular surface are more complicated and sometimes seemingly contradictory. Estrogen receptors are present throughout ocular surface structures, but research suggests that estrogen may actually oppose some benefits of androgens on meibomian gland function 1 .
Studies indicate that estrogen can suppress genes involved in lipid synthesis and stimulate those involved in lipid breakdown, potentially reducing the quality of the tear film's oil layer 1 .
| Hormone | Effect on Meibomian Glands | Effect on Lacrimal Glands | Overall Impact on Dry Eye |
|---|---|---|---|
| Androgens | Increase lipid production; Enhance gene expression for lipid synthesis; Reduce ductal keratinization | Support gland structure; Increase secretory function; Modulate immune function | Protective; Deficiency promotes evaporative dry eye |
| Estrogens | Suppress lipid synthesis; Stimulate lipid catabolism; May reduce gland activity | Controversial: may cause gland regression or have beneficial effects | Complex: may promote dry eye in some contexts |
| Progesterone | Limited research; may decrease lipid secretion | Limited research; potential synergistic effects with estrogen | Not fully understood |
A compelling 2025 study published in Scientific Reports set out to evaluate a novel combination therapy for severe dry eye in perimenopausal women 2 . The researchers hypothesized that addressing both systemic hormonal imbalances and ocular surface deficiencies might yield better results than conventional single-approach treatments.
The study enrolled 1249 perimenopausal women with severe dry eye, eventually randomizing 100 patients into five distinct groups:
Age-matched women without perimenopause diagnosis
Severe dry eye patients receiving only general ophthalmic treatment
Estrogen replacement therapy alone
Autologous serum eye drops alone
Combined estrogen replacement and autologous serum therapy
The findings revealed striking differences between treatment groups. The combination therapy (ERT + AS) demonstrated superior results across multiple parameters compared to either treatment alone or control conditions.
Tear film stability showed dramatic improvement in the combination group, reaching near-normal values compared to control and single-treatment groups 2 .
| Parameter | Normal Group | Control Group | ERT Only | AS Only | ERT + AS |
|---|---|---|---|---|---|
| Tear Break-up Time (s) | 15.16 ± 0.73 | 5.11 ± 0.45 | 8.27 ± 0.59 | 8.15 ± 0.72 | 13.37 ± 0.85 |
| Schirmer Test (mm) | Baseline | Lowest | Moderate | Moderate | Highest |
| Inflammatory Markers | Baseline | Highest | Reduced | Reduced | Most reduced |
| Tear Quality Components | Baseline | Lowest | Increased | Increased | Most increased |
This study provides compelling evidence that addressing dry eye in perimenopausal women requires a multifaceted approach that targets both systemic hormonal balance and local ocular surface health. The superior results from the combination group suggest synergistic benefits—estrogen therapy likely created a more favorable systemic environment, while autologous serum provided immediate local support with essential tear components 2 .
| Reagent/Method | Function/Application | Research Example |
|---|---|---|
| Autologous Serum | Natural tear substitute containing growth factors, vitamins, and immunologic components; promotes ocular surface healing | Used as eye drops in clinical studies; provides essential components missing in artificial tears 2 |
| Enzyme-Linked Immunosorbent Assay (ELISA) | Detects and quantifies specific proteins (cytokines, hormones) in biological samples | Measured inflammatory markers (VEGF, IL-1β, TNF-α) and tear components (lysozyme, lactoferrin) in study participants 2 |
| Sex Hormone Receptor Analysis | Identifies presence and density of hormone receptors in ocular tissues | Confirmed androgen, estrogen, and progesterone receptors in meibomian glands, lacrimal glands, and corneal tissues 1 7 |
| Gene Expression Profiling | Measures activity of genes in specific tissues under different hormonal conditions | Identified androgen-regulated genes involved in lipid production in meibomian glands 1 |
| Animal Models | Allows controlled manipulation of hormone levels and observation of effects | Used to demonstrate that androgen deficiency causes meibomian gland dysfunction reversible with testosterone 3 |
While systemic estrogen replacement alone may worsen dry eye symptoms, targeted topical applications and androgen-based treatments show promise.
Recent research has investigated perfluorohexyloctane eye drops, which demonstrated effectiveness across different hormonal statuses 9 .
The success of autologous serum points toward the potential of customized tear replacements containing specific growth factors and anti-inflammatory components.
Recent research has revealed that the relationship between hormones and eye disease extends beyond dry eye. A 2025 preclinical study discovered that female sex hormones can significantly enhance the progression of retinitis pigmentosa, a rare neurodegenerative eye disease 4 .
When researchers depleted sex hormones in female mice with this condition, disease progression slowed dramatically. This groundbreaking finding suggests that hormonal effects on the eye are far more extensive than previously recognized.
Another emerging area of research focuses on how chemicals in our environment may be influencing hormonal eye health through their action as endocrine disruptors. Chemicals found in cosmetics and personal care products—including phthalates, parabens, and tea tree oil—can mimic or interfere with natural hormones 8 .
These disruptors often have estrogen-like or anti-androgen activities that may adversely affect meibomian gland function and promote dry eye.
The future of dry eye treatment appears to be moving toward personalized approaches that consider an individual's hormonal status, age, gender, and environmental exposures. As Dr. Anna Tichenor, recipient of the 2024 AOA Investigator Initiated Research Award, notes: "We need more research in understanding the development and progression of dry eye disease in women" 5 .
Her current work focuses on measuring sex hormones in tears to understand how they change with age and contribute to dry eye—a step toward more targeted treatments.
The journey to understand the connection between sex hormones and dry eye has transformed our perspective on this common condition. What was once viewed primarily as a local ocular surface disorder is now recognized as a complex neuroendocrine condition influenced by systemic factors, particularly hormonal balance.
This evolving understanding offers hope for the millions who struggle with dry eye symptoms. It suggests that effective management may require looking beyond traditional artificial tears to consider systemic health, hormonal status, and environmental factors.
For patients experiencing dry eye, particularly women at different life stages or those undergoing hormonal changes, these advances underscore the importance of comprehensive evaluation and management. The eyes, it turns out, are not isolated organs but windows into our complex hormonal landscape—and understanding this connection may be the key to preserving both comfort and vision.