The Role of Menopausal Hormone Therapy in Hormone-Dependent Carcinogenic Mechanisms in the Oral Cavity: A Literature Review

Across the world, the incidence of oral squamous cell carcinoma (OSCC) is increasing, establishing it as one of the most prevalent cancers originating in the oral cavity. Estrogen Receptor alpha (ERα) and Estrogen Receptor beta (ERβ) expression were identified and analyzed in normal oral mucosa as well as in squamous cell carcinoma. On a molecular level, estrogens and progestogens, as steroid hormones, influence various biological processes, including reproduction and behavior, by binding to their intracellular receptors. Hypotheses suggest that oral cavity malignancies could be hormonally induced. Periodontal inflammation, mediated by TREM-1, IL-1β, and reduced salivary antibacterial function during hormonal fluctuations, is important in evaluation of etiology of oral cancers and is correlated to hormonal levels. Focal adhesion kinase (FAK) signaling activates ERα through phosphorylation, increasing its transcriptional activity and promoting cell proliferation. Menopausal hormone therapy (MHT) offers both hormonal and non-hormonal treatments, with concerns about overprescription and potential off-label use. In this literature review we aimed to analyze whether there is a link between MHT which consists of estrogen or both estrogen and progesterone and oral cancer risk. A review of the scientific literature covering the years 2018-2025 was carried out, whether estrogens, identified as carcinogens, may be suggested as the potential therapeutic target for OSCC in the future, similar to their well grounded role in the standard management of estrogen receptor-positive breast cancer.