Objective: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ER), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. Design: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list. Ten postmenopausal women were treated with transdermal 17-estradiol 50 μg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17-estradiol 300 μg/day (one spray delivery of 150 μg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C). All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ER, VIP, SP, and NPY were performed in groups A and B before and after 6 months of HT and in group C. Results: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ER, and SP. HT induced a significant increase in E2, ER, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. Conclusions: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.
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