Melanoma-specific risk associated with hormone replacement therapy and fertility treatments: A narrative review and a clinical guide

The relationship between melanoma and female hormonal factors has long been a subject of investigation. While pregnancy-associated melanoma (PAM) has been widely studied, current evidence does not consistently demonstrate an increased risk of developing melanoma during pregnancy or a worse prognosis in pregnant women with pre-existing disease. This narrative review expands the scope beyond PAM, focusing specifically on the potential impact of hormone replacement therapy (HRT) and fertility treatments on melanoma risk and progression. We performed a comprehensive review of the literature, analyzing studies that explored the association between exogenous hormonal exposure and melanoma development, recurrence, or progression. Available evidence is often conflicting and limited by methodological heterogeneity. Some studies suggest a possible increased risk of melanoma with prolonged use of certain hormonal agents, particularly oral contraceptives and fertility drugs, while others do not support a significant association. The influence of these treatments on prognosis remains unclear. Our goal is to provide clinicians with a critical synthesis of existing data and practical insights for managing younger female patients with melanoma or at risk of melanoma. This review underscores the importance of individualized risk assessment and shared decision-making when hormonal therapies are considered in this setting. Further prospective studies are needed to clarify these associations and inform evidence-based clinical guidelines.