Rossing M A, Daling J R, Weiss N S, Moore D E, Self S G
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Melanoma Res. 1995 Apr;5(2):123-7. doi: 10.1097/00008390-199504000-00009.
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.
1974年至1985年间,我们在华盛顿州西雅图的不孕不育诊所对3837名女性进行了评估,以研究排卵异常及使用促排卵药物(如枸橼酸氯米芬)与皮肤恶性黑色素瘤风险之间的关系。通过与基于人群的肿瘤登记处进行计算机链接,来识别在1992年前被诊断为黑色素瘤的女性。从癌症患者及随机抽取的亚队列女性的不孕不育诊所病历中提取有关不孕不育检查和治疗的数据。该队列中有12名女性患上了皮肤恶性黑色素瘤,而预期病例数为6.8例(标准化发病率比 = 1.8;95%置信区间(CI)0.9 - 3.1)。在该队列中,使用氯米芬达12个或更多月经周期的女性风险增加(相对风险 = 2.2;95%CI 0.5 - 10.2)。使用氯米芬达到此疗程且患上黑色素瘤的4名女性均有排卵异常,其中3名还使用了人绒毛膜促性腺激素(HCG)。在未暴露于氯米芬至少12个周期的情况下,未观察到排卵异常与风险升高有关;同样,在无排卵异常的女性中,长期使用氯米芬也未增加风险,但此类女性数量很少。因此,尚不确定该队列中观察到的黑色素瘤风险增加(若不是由于偶然因素)在多大程度上可能归因于氯米芬或HCG的使用,还是反映了使用该药物所针对的某些潜在激素异常。