LeBlanc G A, Kantoff P W, Ng S F, Frei E, Waxman D J
Department of Biological Chemistry, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Cancer. 1992 May 1;69(9):2306-10. doi: 10.1002/1097-0142(19920501)69:9<2306::aid-cncr2820690917>3.0.co;2-f.
Patients with testicular cancer treated with cisplatin can undergo feminization that is understood poorly. Rat model studies recently showed that cisplatin can feminize in part the profile of hepatic steroid-metabolizing enzymes and circulating hormone levels. This study was undertaken to determine whether cisplatin similarly might contribute to the perturbations in gonadotropin or steroid hormone levels that can occur in patients undergoing cisplatin-based treatment for testicular cancer. Analysis of serum free testosterone, total testosterone, and androstenedione levels revealed that these hormones were not altered significantly in patients during a 38-week period of cisplatin-based treatment and follow-up. Estradiol levels were elevated before chemotherapy and were reduced to normal levels during treatment. This reduction was attributed to the cytotoxic effect of chemotherapy on the tumors and the resultant reduction in serum chorionic gonadotropin levels. Serum dihydrotestosterone (DHT) levels were normal before chemotherapy but progressively became elevated during treatment with cisplatin in five of ten patients examined. The rise in DHT may relate to the previously described increase in hepatic androgen 5 alpha-reductase activity in cisplatin-treated rats. Levels of the gonadotropins, luteinizing hormone, and follicle-stimulating hormone (FSH) were normal before cisplatin-based treatment was administered; however, FSH was elevated selectively during chemotherapy. This selective induction of FSH may reflect an effect of cisplatin on the hypothalamic secretion of gonadotropin-releasing hormone. Taken together, these findings suggest that cisplatin contributes to the perturbation of steroid and peptide hormone levels in patients with testicular cancer and perhaps in others undergoing cisplatin-based chemotherapy.
接受顺铂治疗的睾丸癌患者会出现难以理解的女性化现象。大鼠模型研究最近表明，顺铂可部分使肝脏类固醇代谢酶谱和循环激素水平女性化。本研究旨在确定顺铂是否同样可能导致接受基于顺铂的睾丸癌治疗的患者出现促性腺激素或类固醇激素水平的紊乱。对血清游离睾酮、总睾酮和雄烯二酮水平的分析显示，在基于顺铂的治疗和随访的38周期间，这些激素在患者中没有显著改变。雌二醇水平在化疗前升高，在治疗期间降至正常水平。这种降低归因于化疗对肿瘤的细胞毒性作用以及血清绒毛膜促性腺激素水平的相应降低。血清双氢睾酮（DHT）水平在化疗前正常，但在接受检查的10名患者中有5名在顺铂治疗期间逐渐升高。DHT的升高可能与先前描述的顺铂处理的大鼠肝脏雄激素5α-还原酶活性增加有关。在给予基于顺铂的治疗之前，促性腺激素、黄体生成素和促卵泡激素（FSH）水平正常；然而，FSH在化疗期间选择性升高。FSH的这种选择性诱导可能反映了顺铂对促性腺激素释放激素下丘脑分泌的影响。综上所述，这些发现表明顺铂导致睾丸癌患者以及可能其他接受基于顺铂化疗的患者的类固醇和肽激素水平紊乱。
