Hormonal influence on melanoma outcomes: A retrospective analysis of estrogen and progesterone therapies

Summary: Abstract Body: This study investigates the effects of estrogen and progesterone therapies on mortality in melanoma patients, aiming to clarify their influence on outcomes. Using TriNetX, a global database of de-identified patient data, we conducted a retrospective cohort analysis. Adult melanoma patients (≥18 years) exposed to estrogen (n=10,227), progesterone (n=718), or both hormones (n=34,549) were compared to controls without hormone exposure (n=313,691). Propensity score matching adjusted for demographics and common indications for hormone use. Mortality risk was calculated, and Kaplan-Meier survival curves were generated over a 5-year period, excluding patients diagnosed more than 20 years ago. After matching, estrogen-exposed melanoma patients had significantly decreased mortality compared to control melanoma patients not exposed to estrogen (n=9,136; HR 0.645, 95% CI 0.576–0.721, p=0.039). Conversely, melanoma patients exposed to both estrogen and progesterone showed significantly increased mortality (n=30,996; HR 1.41, 95% CI 1.339–1.484, p<0.001). Progesterone exposure alone showed no significant impact on mortality (n=685; HR 1.158, 95% CI 0.772–1.738, p=0.950). To validate melanoma’s contribution to mortality, comparisons were made with matched controls without melanoma, confirming higher mortality and reduced survival in melanoma patients across all groups. These findings suggest that estrogen therapy may confer a survival benefit in melanoma patients, while combined estrogen and progesterone therapies are associated with worse outcomes. Preclinical evidence of protective estrogen receptor signaling aligns with our observations, underscoring the complexity of hormonal influences on melanoma. Future studies are needed to elucidate the biological mechanisms and optimize treatment strategies. Tara McCaffrey¹, Raghav Tripathi¹, Abigail Fleischli¹, Kristin Bibee² 1. Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States. 2. Dermatology, University of Virginia School of Medicine, Charlottesville, VA, United States. Clinical Research: Epidemiology and Observational Research