Exogenous Hormone Factors in Relation to the Risk of Malignant Melanoma in Women: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Many epidemiological studies have examined the relationship between cutaneous malignant melanoma (CMM) and both endogenous oestrogen exposure (e.g., age at menarche and parity) and exogenous hormone use (e.g., oral contraceptives (OCs) and menopausal hormone therapy (MHT)). Though a previous meta-analysis investigating the relationship between characteristics of female endocrine status and CMM risk found no significant association, the potential role of THERAPY AS oral contraceptive (OC) and hormonal replacement therapy (MHT) use still remains controversial. Since then, several studies have been published about the therapy with contrasting results, while CMM incidence continues to increase with a significant gender divergence. The therapy of OC and MHT may play a role in CMM and the removal of this could be useful as emerging therapeutics in melanoma. Therefore, we conducted this systematic review and meta-analysis to summarize the evidence and derive a more accurate estimation of exogenous hormone factors in women and CMM. ABSTRACT: The influence of exogenous female hormones on the risk of developing malignant melanoma in women remains controversial. The aim of our review and meta-analysis is to summarize the evidence and derive a more accurate estimation of the association between oral contraceptives (OCs) or menopausal hormone therapy (MHT) and the risk of developing malignant melanoma in women. PubMed, Web of Science, and Scopus database were searched for studies published up until October 2021. The PRISMA statement and MOOSE guidelines were followed. Studies were pooled using a random effects model. Heterogeneity was explored with the chi-square-based Cochran’s Q statistic and the I(2) statistic. Publication bias was assessed with Begg’s test and Egger’s test. Forty-six studies met the eligibility criteria. The pooled analysis (26 studies) on OC use and the risk of developing cutaneous malignant melanoma (CMM) showed no significant association, but demonstrated significant association for cohort studies (OR 1.08, 95% CI 1.01–1.16; I(2) = 0.00%, p = 0.544). The pooled analysis (16 studies) showed a significantly increased risk of CMM in association with MHT (OR 1.15, 95% CI 1.08–1.23; I(2) = 25.32%, p = 0.169). Stratifying the results by study design showed that a significant increased risk of CMM was associated with MHT in the cohort studies (OR 1.12; 95% CI 1.04–1.19; I(2) = 0%, p = 0.467). No significant publication bias could be detected. Further studies are needed to investigate the potential association with formulation, duration of use, and dosage of use, and to better understand the role of possible confounders.