Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis

Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥5 years [pooled RR=1.18; 95% CI: 1.07–1.31; I(2)=0%] and ≥10 years [pooled RR=1.25; 95% CI: 1.06–1.48; I(2)=0%]). Women who first used OC 15–19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03–2.24; I(2)=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02–1.24; I(2)=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17–1.37; I(2)=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.