A Narrative Review of the Role of Estrogen (Receptors) in Melanoma

Abstract

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field.

Keywords: cutaneous melanoma; estrogen; estrogen receptor; hormone replacement therapy; menarche; menopause; oral contraceptives; parity; pregnancy.

Figure 1

Flow diagram according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis [107] with the detailed search process on 30 December 2022. * Time limit from 2002 up to and including 2022 ** No conference abstracts were used because they are of no use in this narrative review. Remarks: no published search filters were used.

Figure 2

An overview of the role of estrogen (receptors) in melanoma (created with BioRender.com). Abbreviations: ER⍺ = estrogen receptor alpha, ERβ = estrogen receptor beta, GPER1 = G-protein-coupled estrogen receptor 30/1, ♀ = women, ♂ = men, OC = oral contraceptive, HRT = hormone replacement therapy, IVF = in vitro fertilization, hCG = human chorionic gonadotrophin, GnRH = gonadotrophin-releasing hormone.