Estrogen Exposure is Associated With Reduced Otosclerosis Risk in Obesity and Hormone Therapy

Objective: To examine whether conditions associated with elevated-estrogenic states, including obesity, type 2 diabetes mellitus (T2DM), and postmenopausal estradiol hormone replacement therapy (HRT), are associated with the development of otosclerosis. Methods: We performed 3 retrospective cohort analyses using the US TriNetX network. Population included adults ≥18 years of age with an ear evaluation (the International Classification of Diseases [ICD]-10 Z01.1). Exposures included obesity (ICD-10 E66), T2DM (ICD-10 E11), and HRT (RxNorm 4083). Primary outcome of interest was otosclerosis (ICD-10 H80). Exclusion criteria for obesity and T2DM cohorts included type 1 diabetes (ICD-10 E10); for all cohorts, criteria included congenital ear abnormalities (ICD-10 Q16) or outcome of interest ≥20 years ago. 1:1 propensity score matching was performed on each cohort for demographics, metabolic comorbidities, ototoxic medications, lifestyle, body mass index, age, and sex. Relative risk with 95% confidence intervals was calculated; P < 0.05 represents statistical significance. Results: Otosclerosis occurred in 25 individuals with obesity with 52 controls (risk ratio [RR] = 0.48, P < 0.005). In the T2DM cohort, 15 cases were present, whereas the control population had 27 cases (RR = 0.56, P = 0.06). Among the estradiol HRT cohort, 303 cases were present compared with 369 in control (RR = 0.82, P < 0.05). Conclusions: Obesity and estradiol HRT are associated with a decreased risk of developing otosclerosis. A similar but nonsignificant trend was found in patients with T2DM. This suggests a protective role of estrogen against otosclerosis. Future studies may serve to elucidate longitudinal hormone profiling and identify a therapeutic local intervention for individuals with otosclerosis.