Female melanoma patients generally exhibit significantly longer survival than male patients. This population-based cohort study aimed to investigate gender differences in survival and disease progression across all stages of cutaneous melanoma. A total of 11,774 melanoma cases extracted from the Munich Cancer Registry (Germany), diagnosed between 1978 and September 2007, were eligible to enter the study. Hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for tumor and patient characteristics, were estimated for the end points of survival, regional and systemic progression, and survival after progression. A significant female advantage was observed for melanoma-specific survival (adjusted HR 0.62; 95% CI 0.56-0.70). Women were at a lower risk of progression (HR 0.68; 95% CI 0.62-0.75), including a lower risk of lymph node metastasis (HR 0.58; 95% CI 0.51-0.65) and visceral metastases (HR 0.56; 95% CI 0.49-0.65). They retained a significant survival advantage after first progression (HR 0.81; 95% CI 0.71-0.92) and lymph node metastasis (HR 0.80; 95% CI 0.66-0.96), but this became borderline significant (HR 0.88; 95% CI 0.76-1.03) after visceral metastasis. Localized melanomas in women had a lower propensity to metastasize, resulting in a better survival when compared with men, even after first disease progression. These results suggest differences in tumor-host interaction across gender.

Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.

Our study suggests a cumulative dose-dependent increased risk of CM with the use of estrogens.