Unraveling the controversy: exploring the link between sex hormones and skin cancers through a meta-analysis and systematic review

Skin cancers continue to present unresolved challenges, particularly regarding the association with sex hormones, which remains a topic of controversy. A systematic review is currently warranted to address these issues. To analyze if sex hormones result in a higher incidence of skin cancers (cutaneous melanoma, basal cell carcinoma, squamous cell carcinoma). Data sources and study selection-The database of PubMed, Embase and Web of Science (WOS) was searched until July 3, 2024. The search yielded 1016 articles. 42 eligible studies were identified for meta-analysis. Data extraction and synthesis-Eligible trials reported skin cancer data and outcomes, confirming diagnoses and collecting hormone use information. Other extracted data included study methods, demographics, and reproductive factor. Relative risk (RR) and odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI), were synthesized after adjusting. The primary outcome was the incidence of cutaneous melanoma and non-cutaneous melanoma. 95% CI and OR are estimate effects. Participants using oral contraceptives (OCs) showed a higher incidence of cutaneous melanoma (CM) [OR 1.08, 95%CI 1.03-1.13, p < 0.01]. There is positively related statistic difference in Squamous cell carcinoma (SCC) [OR 1.37, 95%CI 1.15-1.63, p < 0.01]. Hormone replacement therapy (HRT) was associated with a higher incidence of CM [OR 1.18, 95%CI 1.13-1.24, p < 0.01]. And for non-melanoma skin cancer (NMSC), HRT also increased the incidence [OR 1.13, 95%CI 1.03-1.24, p = 0.01]. Menopausal hormone therapy (MHT) also showed an increased incidence of CM [OR 1.09, 95%CI 1.00-1.18, p < 0.05]. For age at first birth, > 30 years demonstrated a positive correlation with increased the incidence of CM [OR 1.21, 95%CI 1.00-1.46, p = 0.05]. OCs and HRT were associated with increased risks of skin cancers. MHT elevated the risk of CM. In women whose menopause age was older than 50 years, endogenous sex hormones decreased gradually, which caused higher risks of skin cancers. First birth aged older than 30 years indicated increasing effects of skin cancers.Trial registration number : CRD42024517445.