Background: Autoimmune associated vocal fold lesions (AaVFL) are a result of underlying autoimmune conditions that include laryngeal rheumatoid nodules, bamboo nodules, and other non-specific disease lesions. Women being more prone to autoimmune disease are therefore more likely to develop these vocal fold lesions. This relationship showed a greater association in women in their 4th and 5th decade when treating these lesions. This greater association is theorized to be due to introduction of hormone replacement therapy (HRT) containing estrogen in their 4th and 5th decades of life. The pro-inflammatory nature of estrogen in women with autoimmune disease and the presence of estrogen receptors on cells within vocal fold tissue presents a potential pathway for development of these lesions.

Results: In this retrospective cohort study, we used TriNetX a deidentified global patient database to perform a comparative risk analysis of two cohorts: women with underlying autoimmune conditions who have or haven’t been exposed to HRT containing estrogen. The underlying autoimmune conditions queried for were rheumatoid arthritis, systemic lupus erythematous, sjögren syndrome, autoimmune thyroiditis, sarcoidosis, amyloidosis, scleroderma, and relapsing polychondritis. Risk analysis showed a statistically significant 1.65 times higher risk of developing a vocal fold lesion when exposed to HRT containing estrogen.

Conclusion: This comparative risk analysis supports a relationship between the development of a AaVFL after the exposure to HRT containing estrogen in women. Evidence of this relationship supports further research into the estrogen-estrogen receptor complex pathway within the larynx and altering clinical procedures for treating patients with AaVFL on HRT containing estrogen.