HORMONAL AND REPRODUCTIVE FACTORS IN MELANOMA RISK

It is difficult to trace when and why the question arose of a possible relationship between female hormones and the risk of malignant melanoma of the skin. Beral et al, in the late seventies, reported for the first time a positive association between oral contraceptive (OC) use and malignant melanoma of the skin and thus suggested a causal relationship.1 Another reason could be observations of higher incidence rates in premenopausal women compared with men of the same age.2 Moreover, the hormone hypothesis may have been nourished by such early observations as benign hyperpigmentation during pregnancy as well as during OC use, or following menopausal estrogen replacement and topical estrogen treatment.3. Early laboratory data on steroid receptors suggested the existence of estrogen receptors on melanocytes and melanoma cells,4 but more recent investigations have been unable to identify all requirements defining a specific receptor. It has been proposed that the apparent receptor may to some extent bind to the enzyme tyrosinase. 5 Clinical trials on the antiestrogen tamoxifen have been negative.6,7 Very few patients responded, and there was no relationship between receptor levels and probability of response. Finally, epidemiologic data clearly prove a higher melanoma mortality in men compared with women and multivariate analyses of clinical series have shown that male gender is a separate, negative prognostic factor.8 There is no good theoretical explanation of why estrogens should increase the risk of melanoma but retard growth and dissemination of the tumor. Therefore, it is very important to obtain epidemiologic evidence for possible relationships between female hormones and risk of melanoma, especially because OCs have been suspected of increasing melanoma risk. A number of case-control studies and a couple of cohort studies from the 1980s focused on possible relationships between characteristics of female endocrine status and the risk of melanoma. The studies included questions about use of OCs and postmenopausal estrogen therapy, and parity and age at menarche, menopause, and first childbirth, which reflect influences of exogenous and endogenous hormones, respectively. © 1992.