Risk of cutaneous melanoma in a cohort of infertile women

We assessed the risk of cutaneous malignant melanoma associated with the presence of ovulatory abnormalities and with the use of ovulation-inducing agents (such as clomiphene citrate) in a cohort of 3,837 women evaluated at infertility clinics in Seattle, WA, between 1974 and 1985. Computer linkage with a population-based tumour registry was used to identify women diagnosed with melanoma before 1992. Data regarding infertility testing and treatment were abstracted from the infertility clinic medical records for women who developed cancer and a randomly selected subcohort. Twelve women in the cohort developed cutaneous malignant melanoma, in comparison with an expected number of 6.8 cases (standardized incidence ratio = 1.8; 95% confidence interval (CI) 0.9-3.1). Within the cohort, risk was increased among women who had used clomiphene during 12 or more menstrual cycles (relative risk = 2.2; 95% CI 0.5-10.2). All four of the women with this duration of clomiphene use who developed melanoma had ovulatory abnormalities, and three had also used human chorionic gonadotropin (HCG). No elevation in risk associated with the presence of ovulatory abnormalities was observed in the absence of at least 12 cycles of clomiphene exposure; also, there was no increased risk associated with long-term use of clomiphene among women without ovulatory abnormalities, but the number of such women was very small. Thus, it is not certain to what extent the observed increased risk of melanoma in this cohort (if not due to chance) may be attributable to the use of clomiphene or HCG, or is a reflection of some underlying hormonal abnormality for which the drug was administered.