Salivary glands in menopause: impacts of hypoestrogenism on microvasculature and nitric oxide metabolismo

• Grant number: 25/15951-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Giovanna Piacenza Florezi
• Grantee: Sofia Pantarotto
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/12807-5 - Xerostomia in pre and post-menopause and its interface with women's oral health: investigation from bench to bedside, AP.TEM

Abstract

Menopause is a physiological condition marked by a decline in estrogen levels, affecting multiple systems, including the cardiovascular, immune, and oral environments. Among the frequently reported symptoms in postmenopausal women is xerostomia-a subjective sensation of dry mouth-which is not always associated with a measurable reduction in salivary flow, but may result from changes in its composition. Saliva is critical in maintaining oral homeostasis and is involved in metabolic pathways linked to nitric oxide (NO), a potent vasodilator with anti-inflammatory properties whose production may be influenced by circulating hormone levels. NO is produced endogenously by nitric oxide synthase (NOS) and through an alternative nitrate-nitrite-NO-pathway mediated by the oral microbiome. Aging and hypoestrogenism can reduce NO bioavailability, contributing to endothelial dysfunction, increased oxidative stress, and possibly alterations in salivary gland physiology. Despite its clinical relevance, the relationship between estrogen deficiency, NO production, and salivary alterations during menopause remains poorly understood. This project aims to investigate the influence of hypoestrogenism and hormone replacement therapy on salivary nitric oxide levels and on morphological changes in the salivary glands of postmenopausal women. The study will assess salivary nitrate and nitrite levels, and analyze the expression of estrogen receptors, nitrate transporters (sialin), microvascular density markers (CD31), and membrane permeability proteins (AQP1 and AQP5), to understand the mechanisms involved in xerostomia in this context. The findings of this study are expected to contribute to a deeper understanding of the systemic effects of estrogen deficiency in nitric oxide production and on salivary gland function to support the development of targeted therapeutic strategies for oral health in menopausal women.