A Meta-analysis Of The Effects Of Exogenous Hormones And Reproductive Factors On Female Melanoma

Objective:Since the 1970s,many epidemiological studies have focused on the possible relationship between female endocrine characteristics and melanoma,but there has been considerable debate about the potential impact of hormones on melanoma risk.We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women.Methods:We performed a search of Pub Med,Web of Science,and the China National Knowledge Infrastructure(CNKI)database for relevant studies,and the retrieval time was from the establishment of the database to April 2020.We included all studies that reported relative risks with 95%confidence intervals(CI)for an association between oral contraceptives(OC),hormone replacement therapy(HRT),and reproductive factors(including parity,age of first child,age of menarche,and menopausal status)and the risk of melanoma in women.The literature was screened according to the preset inclusion and exclusion criteria,and the quality evaluation and data extraction were carried out for the included literature.Based on heterogeneity,Revman5.3 software was used to perform the Meta-analysis of the risk estimates using fixed effect model or random effect model.Results:We identified 38 studies that met the inclusion criteria,including 20 case-control studies,14cohort studies,3 nested case-control studies,and 1 study that included both cohort and case-control studies,involving 3571,910 participants.The results are as follows:1.Long-term use of 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%]).2.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.3.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.4.With regard to reproductive factors,Fewer parities 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.Conclusions:1.Long-term use of OC may increase the risk of melanoma in women,and that an incubation period of 15 to 19 years may be required to increase the risk of melanoma.However,the age at first use of OC and years since last use of OC is not associated with melanoma.2.HRT use is associated with an increased incidence of melanoma in women,especially with an increased risk of SSM,and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma.3.Fewer parities and age≥20 years at the first birth were associated with an increased risk of melanoma in women,while menopausal status,and age at menarche were not associated with the incidence of melanoma in women.