Cellular and Molecular Alterations in the Oral Mucosa During the Menopausal Transition: A Scoping Review

This project is a scoping review titled “Cellular and Molecular Alterations in the Oral Mucosa During the Menopausal Transition: A Scoping Review.” The purpose of this review is to map, describe, and synthesize the available evidence on cellular and molecular alterations affecting the oral mucosa during the menopausal transition, including perimenopause, menopause, postmenopause, and estrogen-deficient states. The menopausal transition is characterized by progressive endocrine changes, particularly fluctuations and decline in estrogen levels. These hormonal changes may influence oral tissues and contribute to oral manifestations such as xerostomia, burning mouth symptoms, mucosal discomfort, mucosal fragility, altered wound healing, changes in oral epithelial barrier function, and increased susceptibility to inflammation or infection. However, the cellular and molecular mechanisms underlying these oral mucosal alterations remain dispersed across different areas of research, including clinical studies, histological studies, immunohistochemical analyses, salivary biomarker studies, microbiome research, in vitro models, and animal studies. This scoping review will focus on the oral mucosa, oral epithelium, oral keratinocytes, and related oral mucosal tissues. It will explore evidence regarding estrogen receptor expression and signaling, epithelial proliferation and differentiation, apoptosis, cellular senescence, epithelial atrophy, barrier integrity, tight junction and adhesion molecules, inflammatory pathways, oxidative stress, immune mediators, gene and protein expression, microbiome-related changes, and other mechanisms potentially involved in oral mucosal homeostasis during the menopausal transition. The review will be conducted according to the Joanna Briggs Institute methodology for scoping reviews and will be reported following the PRISMA-ScR guidance. The eligibility criteria will be structured using the Population–Concept–Context framework. The population will include peri-menopausal, menopausal, and postmenopausal women, as well as relevant estrogen-deficient experimental models. The concept will include cellular, molecular, histological, immunohistochemical, microbiological, salivary, and mechanistic alterations. The context will be the oral mucosa and related oral epithelial tissues, including buccal, gingival, lingual, palatal, and other oral mucosal sites. Electronic searches will be performed in PubMed/MEDLINE, Cochrane CENTRAL, Scopus, and Web of Science Core Collection. Additional sources may include reference lists of included studies, citation tracking of relevant articles, and other sources considered appropriate for identifying evidence. No initial date restriction will be applied. Search strategies will combine terms related to the menopausal transition, estrogen deficiency, oral mucosa or oral epithelium, and cellular or molecular mechanisms. The expected outcomes of this project are: first, to provide a comprehensive map of the types of evidence available on oral mucosal cellular and molecular alterations during the menopausal transition; second, to identify the main biological mechanisms that have been investigated; third, to clarify which oral mucosal tissues, cell types, biomarkers, and pathways have received greater or lesser attention; and fourth, to identify knowledge gaps that may guide future mechanistic, translational, and clinical research. The review may also inform the biological rationale for future interventions aimed at preserving or restoring oral mucosal homeostasis in women during and after the menopausal transition.