The effect of menopausal hormone therapy on the risk of melanoma and keratinocyte skin cancer: A systematic review and meta-analysis of observational studies

Background: Whether menopausal hormone therapy (MHT) increases the risk of skin cancer is controversial. Aim: To systematically review and meta-analyze evidence regarding the association of MHT with the risk of melanoma and keratinocyte cancer (KC).Material and methods: A comprehensive literature search was conducted of the PubMed, Scopus and Cochrane databases, through to 30 October 2021. Skin neoplasms were divided into melanoma and KC. In the latter category, both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were considered. The results are presented as hazard ratios (HR) with 95 % confidence intervals (CI). The I2 index was used to assess hetero-geneity. Subgroup analysis and sensitivity analysis were also conducted in order to explore potential differences among studies.Results: Twenty-seven studies were included in the qualitative and 23 in the quantitative analysis, with a total of 2,612,712 menopausal women (25,126 with skin cancer; 20,150 with melanoma). MHT was associated with an increased risk of melanoma (HR 1.11; 95 % CI 1.05-1.19; I2 45%). With regard to MHT type, both estrogen monotherapy (HR 1.22, 95 % CI 1.16-1.29; I2 0%) and estrogen in combination with progestogen (HR 1.11, 95 % CI 1.05-1.18, I2 26%) significantly increased that risk. Regarding melanoma subtype, superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) were the only histologic subtypes associated with MHT use. MHT was also associated with an increased risk of KC (HR 1.17, 95 % CI 1.04-1.31, I2 83%), specifically BCC (HR 1.22, 95 % CI 1.12-1.32; I2 29%). Longer duration (>5 years) of MHT, current use and estrogen mono -therapy were associated with an increased KC risk compared with no use.Conclusion: The use of MHT by postmenopausal women was associated with an increased risk of melanoma and KC. This risk was higher for current MHT users and those treated for over 5 years.