{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:19:57Z","timestamp":1787498397250,"version":"build-2736575974"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We performed 3 retrospective cohort analyses using the US TriNetX network. Population included adults \u226518 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 \u226520 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;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05 represents statistical significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Otosclerosis occurred in 25 individuals with obesity with 52 controls (risk ratio [RR] = 0.48,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.005). In the T2DM cohort, 15 cases were present, whereas the control population had 27 cases (RR = 0.56,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.06). Among the estradiol HRT cohort, 303 cases were present compared with 369 in control (RR = 0.82,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ono.0000000000000083","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T17:00:11Z","timestamp":1769101211000},"page":"e083","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Estrogen Exposure is Associated With Reduced Otosclerosis Risk in Obesity and Hormone Therapy"],"prefix":"10.1097","volume":"6","author":[{"given":"Maia","family":"Smith","sequence":"first","affiliation":[{"name":"John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhanvan","family":"Iyer","sequence":"additional","affiliation":[{"name":"John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney E.S.","family":"Clark","sequence":"additional","affiliation":[{"name":"John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Warren","sequence":"additional","affiliation":[{"name":"John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"McKinnon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The University of Texas Medical Branch, Galveston, TX."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,3]]},"reference":[{"key":"R2-20260122","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.heares.2008.12.004","article-title":"The effect of sex hormones on bone metabolism of the otic capsule \u2013 an overview.","volume":"252","author":"Horner","year":"2009","journal-title":"Hear Res"},{"key":"R3-20260122","first-page":"726","article-title":"The association between serum estradiol level and hearing sensitivity in postmenopausal women.","volume":"99","author":"Kim","year":"2002","journal-title":"Obstet Gynecol"},{"key":"R4-20260122","doi-asserted-by":"crossref","first-page":"e98569","DOI":"10.1172\/jci.insight.98569","article-title":"17-\u03b2 estradiol regulates proglucagon-derived peptide secretion in mouse and human \u03b1- and L Cells.","volume":"3","author":"Handgraaf","year":"2018","journal-title":"JCI Insight"},{"key":"R5-20260122","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ajog.2003.06.001","article-title":"Effects of estrogen therapy on hearing in postmenopausal women.","volume":"190","author":"Kilicdag","year":"2004","journal-title":"Am J Obstet 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complex relationship.","volume":"22","author":"Rinonapoli","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R12-20260122","doi-asserted-by":"crossref","DOI":"10.1093\/bjs\/znaf139","article-title":"Potential for error when relying on administrative data.","volume":"112","author":"Zelicha","year":"2025","journal-title":"Br J Surg"},{"key":"R13-20260122","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s40618-023-02196-z","article-title":"Obesity: a gender-view.","volume":"47","author":"Muscogiuri","year":"2024","journal-title":"J Endocrinol Invest"},{"key":"R14-20260122","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/MAO.0b013e3181a86509","article-title":"Genetics of otosclerosis.","volume":"30","author":"Thys","year":"2009","journal-title":"Otol Neurotol"},{"key":"R15-20260122","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1097\/GME.0000000000000878","article-title":"Menopause and postmenopausal hormone therapy and risk of hearing loss.","volume":"24","author":"Curhan","year":"2017","journal-title":"Menopause"},{"key":"R16-20260122","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/GME.0000000000002335","article-title":"Use of menopausal hormone therapy beyond age 65 years and its effects on women\u2019s health outcomes by types, routes, and doses.","volume":"31","author":"Baik","year":"2024","journal-title":"Menopause"}],"container-title":["Otology &amp; Neurotology 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