Systemic Estrogen Therapy Is Associated With Lower Surgical Intervention Rates for Nasal Obstruction

Nasal obstruction is a common symptom encountered in otolaryngology, often arising from a combination of structural and mucosal factors [1]. While nasal anatomy such as septal deviation and turbinate hypertrophy are frequent contributors, underlying mucosal physiology, including inflammation and mucociliary function, plays an important and often underappreciated role in symptom expression [2-4]. A growing body of evidence suggests that sex hormones, particularly estrogen, have effects on the nasal mucosa. Postmenopausal women have been shown to experience increased rates of nasal obstruction, drainage, and olfactory dysfunction compared to premenopausal women, likely due to the decline in circulating estrogen levels [5]. Hormonal changes associated with menopause have been shown to be linked to impaired mucociliary clearance and alterations in nasal epithelial integrity [2, 3, 5]. Prior work has demonstrated that hormone replacement therapy (HRT) may partially reverse these effects, with improvements in nasal airflow resistance, olfaction, and sinonasal symptom burden in small clinical studies [2-5]. Additionally, recent population-level data show that postmenopausal women with chronic rhinosinusitis using HRT have associated lower rates of endoscopic sinus surgery [5]. Despite this emerging evidence, the effect of HRT on the utilization of structural nasal airway surgery remains unknown. We evaluated whether oral estrogen HRT is associated with subsequent septoplasty and inferior turbinate surgery in postmenopausal women with septal deviation and/or turbinate hypertrophy. We hypothesized that HRT would be associated with a lower likelihood of nasal surgery, potentially reflecting a therapeutic effect on nasal symptoms related to estrogen modulation. We performed a retrospective cohort study in the TriNetX Database (accessed August 10, 2025). Eligible patients were women ≥ 55 years with ICD-10 codes for septal deviation (J34.2), turbinate hypertrophy (J34.3), or both. Patients with prior endoscopic sinus surgery, sinonasal malignancy, or cystic fibrosis were excluded. We also excluded those with prior septoplasty or inferior turbinate surgery. We compared women on oral estrogen with women with no documented HRT prescriptions. Other estrogen formulations were not included in the HRT group. Primary endpoints were septoplasty (CPT 30520) and inferior turbinate surgery (CPT 30130/30140/30930) within 5 years of diagnosis. We used 1:1 nearest-neighbor propensity score matching (caliper 0.1 pooled SD) on age, race, chronic rhinosinusitis, nasal polyposis, chronic or vasomotor rhinitis, allergic rhinitis, asthma, and medications (beta blockers, ACE inhibitors). Documentation of over-the-counter therapies (e.g., intranasal fluticasone, saline) was inadequate, so solely prescription-only medications were included in matching. Post-match balance was assessed using standardized mean differences and confirmed with χ2 and t-tests. We report odds ratios (ORs) with 95% CI and p values. The analysis used de-identified data per HIPAA §164.514(a) and was IRB-exempt. Baseline characteristics were balanced after matching (Table 1). The septal deviation cohort was the largest (1016 vs. 1016), followed by turbinate hypertrophy (515 vs. 515) and combined cohorts (septal deviation and turbinate hypertrophy diagnosis, 329 vs. 329). Median follow-up was ∼33 months within a 5-year window. In the turbinate hypertrophy cohort, inferior turbinate surgery occurred in 2.9% with HRT versus 9.0% without HRT (OR = 0.30; 95% CI, 0.16–0.56; p < 0.001; Table 2). In the septal deviation cohort, septoplasty occurred in 2.3% with HRT versus 4.9% without HRT (OR = 0.46; 95% CI, 0.28–0.77; p = 0.002). A significant reduction in septoplasty and turbinate reduction was also seen in the combined diagnosis cohort (2.4% vs. 11.9%; OR = 0.19; 95% CI 0.09–0.40; p < 0.001). Surgical rates are detailed in Table 2. Across three matched cohorts, oral estrogen HRT was associated with lower utilization of septoplasty and inferior turbinate surgery among postmenopausal women with structural nasal diagnoses. To our knowledge, this is the first study to link systemic hormone therapy with subsequent structural nasal airway surgery. These findings extend reports that HRT use is associated with lower rates of sinus surgery and build upon the literature showing estrogen modulates mucociliary function and airflow perception [2-5]. Clinically, these results support balanced counseling for patients who are candidates for medical therapy and surgery. Some women treated with estrogen may achieve adequate symptom control and be less likely to pursue surgery. That being said, despite large relative differences in surgery rates, overall surgery rates were low. Crude retrospective NNT to forgo one associated surgery were ≈16 for turbinate hypertrophy, ≈38 for septoplasty, and ≈11 for combined diagnosis/surgery. This study has several limitations. It is a retrospective study, and we can only identify factors associated with surgery, not causality. Also, we restricted exposure to oral estrogen-only HRT, the most common systemic formulation in this dataset [6, 7]. This was done for consistency but may limit generalizability to other regimens. Some perioperative guidance recommends holding oral HRT several weeks before surgery due to modest thrombosis risk [8-10]. This may lead some HRT users to defer elective procedures, but it is unlikely to explain the full effect we observed. Additionally, excluding those with prior nasal airway surgery may also limit generalizability to revision populations. While our analysis was rigorously matched according to demographics, comorbid diagnoses, and prescription medications associated with nasal obstruction (ACE inhibitors, beta blockers), residual confounding is possible. Ideally, other nasal medications would have been controlled for, but our ability to do this was limited due to unreliable documentation. Also, symptom measures, such as NOSE and SNOT-22, were unavailable. Despite these limitations, the results of this study hold meaningful statistical significance and clinical relevance. Estrogen therapy is already widely available and has an established safety profile in appropriately selected women. A reduction in surgery to this extent has the potential to impact treatment decision-making. Future studies are warranted to better characterize the role of estrogen in nasal physiology and explore whether targeted use of HRT may provide a medical alternative or adjunct for postmenopausal women with nasal obstruction. ChatGPT (OpenAI, GPT-4) was used during the manuscript preparation process to assist with grammatical review and stylistic suggestions. All outputs were critically reviewed, edited, and approved by the authors to ensure accuracy and appropriateness. No AI tools were used to interpret study data or form conclusions. The authors declare no conflicts of interest.