1 Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples Federico II, Via Pansini 5, Italy
2 To whom correspondence should be addressed. Email: cdispie{at}tin.it
Sir,
Caruso and his co-workers in their paper (Caruso et al., 2004) report a favourable effect of hormone replacement therapy (HRT) on olfactory sensitivity in 46 naturally post-menopausal women requiring HRT treatment for climacteric symptoms; moreover, they have demonstrated that both combined and sequential continuous HRT increase significantly nasal airflow, indirectly causing a decrease in olfactory threshold. Furthermore, they did not detect any significant difference between the two routes of administration of estrogens (oral versus transdermal) and the two schedules of administration of HRT (sequential versus continuous). Whilst the authors hypothesize a further direct action of HRT on neuronal transmission of olfactory sensitivity, they did not mention nor hypothesize that the variations of olfactory sensitivity reported in their study could be due to an improved trophism of respiratory nasal mucosa induced by HRT.
Indeed post-menopausal women often complain of paradoxical nasal stuffiness (i.e. a sensation of nasal blockage without swelling of the mucosa and/or anatomical alterations). This sensation seems to be due to a dryness of the nasal mucosa and to an increased viscosity of mucus secretion with a reduced effectiveness of the mucociliary system.
Our study group has investigated extensively the effects of HRT on nasal symptoms and function in post-menopausal women. In a pioneering prospective randomized placebo-controlled study (Nappi et al., 2003), we have demonstrated that 6 months treatment with sequential continuous HRT (transdermal 17
-estradiol plus oral nomegestrole acetate) exerts a positive effect on nasal symptomatology and function in post-menopausal women complaining of paradoxical nasal stuffiness.
In particular, we reported a significant improvement of the feeling of nasal stuffiness, an improved overall appearance of the nasal mucosa at rhinoscopic examination and a significant reduction in mean mucociliary transport time. However, total airway resistance, evaluated by active anterior rhinomanometry, was in the normal range both at baseline and after 6 months of HRT, in evident disagreement with the findings of Caruso and his co-workers.
In order to investigate if HRT could affect nasal function modifying nasal mucosa trophism, we performed two nasal biopsies for each woman at baseline and after 6 months of HRT, evaluating the local concentrations of estradiol and its receptor and of some neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and SP] involved in the regulation of vascular tone and glandular secretion in the nasal mucosa. We have found that HRT influences nasal mucosa function through an effect on functional regulation more than substantially modifying the anatomical structure of this tissue. In fact the reduction in the number of goblet cells and seromucinous glands of lamina propria, which seems to be an important factor in the pathogenesis of post-menopausal nasal complaints, was not reversed by HRT. On the other hand, estrogens might act through an increase in cholinergic (VIP) and sensory (SP) neuropeptides, which stimulate glandular secretion and vasodilatation, and an inhibition of sympathetic (NPY) peptides, causing vasoconstriction.
In a recent paper (Nappi et al., 2004), we have also demonstrated that the effectiveness of intranasally administered HRT (intranasal 17
-estradiol plus oral nomegestrole acetate) in improving nasal function is significantly better than transdermal therapy (transdermal 17
-estradiol plus oral nomegestrole acetate). Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP.
In conclusion, we are firmly convinced that the improved trophism of the respiratory nasal mucosa induced by HRT could contribute to a significant reduction of the olfactory threshold.
References
Caruso S, Grillo C, Agnello C, Di Mari L, Farina M and Serra A (2004) Olfactometric and rhinometric outcomes in postmenopausal women treated with hormone therapy: a prospective study. Hum Reprod 19, 29592964.
Nappi C, Di Spiezio Sardo A, Guerra G, Bifulco G, Testa D and Di Carlo C (2003) Functional and morphologic evaluation of the nasal mucosa before and after hormone therapy in postmenopausal women with nasal symptoms. Fertil Steril 80, 669671.[CrossRef][ISI][Medline]
Nappi C, Di Spiezio Sardo A, Guerra G, Di Carlo C, Bifulco G, Acunzo G, Sammartino A and Galli V (2004) Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women. Menopause 11, 447455.[CrossRef][ISI][Medline]