Abstract

PIP: The matter of sex differences in survival from melanoma is more complex than generally recognized, and at least 6 factors, some of which appear to be interrelated, must be conisdered: location of the primary melanoma; stage of disease at presentation; endocrine factors; immunologic factors; pattern of metastatic spread (i.e., lymphogenic versus hematogenic), and environmental and behavioral characteristics. Extremity melanomas have a more favorable prognosis than axial melanomas, but, after allowance for tumor site, women still fare better than men. There appears to be a stage-by-stage difference in favor of women for survival. This applies to clinical stages (stage 1, local disease; stage 2, regional spread; and stage 3, distant metastases), as well as to pathologic microstages. Some authors have inferred that female advantage disappears once the disease has metastasized. No valid explanation for this observation has ever been advanced, and careful review of the literature reveals a female superiority in survival at stage 2 or stage 3 disease as well as stage 1. Many recent studies have confirmed the ancient impression that the incidence of metastatic disease at the time of diagnosis is higher in men. Men tend to have an equal or shorter history before treatment, yet they have more advanced disease at the time of diagnosis. They have an unfavorable outcome irrespective of lesion site, tumor thickness, histogenetic subtype, and clinical stage of disease. These data suggest that the disease develops more rapidly in men. Thus, the aggressiveness and metastatic potential of cutaneous melanoma is more distinct in the male sex. The exacerbation of melanoma during pregnancy may be due to the increase of estrogens or to the elevated androgen levels. The first possibility is unlikely. The elevation of follicle stimulating hormone, luteinizing hormone, and MSH levels may play a role. Several case-controlled studies have failed to reveal any overall relationship between prior history of oral contraceptive use and the development of melanoma. Because the role of estrogens (and hormones in general) in the course of melanoma is not yet satisfactorily established, oral contraceptives are best avoided. It is concluded that malignant melanoma may be a hormone-responsive tumor, despite the fact that the exact nature of such endocrine factors remains nebulous.