Sex disparities in melanoma outcomes: The role of biology

•The biological basis for the sex disparity in melanoma outcomes is reviewed.•Inherent immune, vitamin D, oxidative stress, hormonal and gene expression processes contribute to the disparity.•Behavior and biology combined cause worsened melanoma prognoses in men.

Melanoma outcomes differ between men and women even when adjusted for prognostic factors such as age, Breslow thickness, body site, ulceration, lymph node dissection, and for treatment, with men having poorer outcomes compared to women. The mechanisms underlying this disparity are not well understood. Behavioral differences between the sexes such as ultraviolet light exposure and health care services utilization have been suggested as contributing, and differences in endogenous biological processes such as immune function, hormonal regulation, oxidative stress response, vitamin D metabolism and sex chromosome gene expression have also been proposed as mechanisms. This review examines the cumulative evidence for biologically based processes that lead to differences in melanoma biology, including inherent sex-based differences in immune function, oxidative stress response and vitamin D metabolism; the complex interplay between sex hormones, the immune system and oxidative stress response; the effect of non-random X chromosome inactivation on tumorigenesis; and the potential contribution of recently identified oncogenes on the Y chromosome.