Dowsett M, Cantwell B, Lal A, Jeffcoate S L, Harris A L
Department of Biochemical Endocrinology, Chelsea Hospital for Women, London, United Kingdom.
J Clin Endocrinol Metab. 1988 Apr;66(4):672-7. doi: 10.1210/jcem-66-4-672.
Twenty-one postmenopausal women with advanced breast cancer were treated with monthly 3.6-mg sc injections of the LHRH agonist goserelin [D-Ser-(But)6, Azgly10-LHRH] to determine whether the resultant endocrine changes could provide an explanation for the clinical responses that occur during therapy with this agent. After 4 weeks, serum gonadotropin levels were less than 10% of pretreatment levels, whereas serum PRL levels did not change. A significant decrease in serum testosterone occurred in 19 of 20 patients; this fall was associated with a 22% fall in serum estradiol levels. Serum androstenedione levels also decreased, but serum estrone and dehydroepiandrosterone sulfate (DHAS) levels did not. The lack of fall in serum DHAS levels indicates that the changes in androgen levels were a result of reduced ovarian secretion, and the reduced estradiol levels were a consequence of reduced precursor (i.e. testosterone) availability. The continued dependence of ovarian androgen secretion on gonadotropin stimulation after the menopause may explain the responses of some patients to LHRH agonists and some other therapeutic agents of unknown or uncertain modes of action.
21名绝经后晚期乳腺癌妇女接受了每月3.6毫克皮下注射促性腺激素释放激素（LHRH）激动剂戈舍瑞林[D-丝氨酸（叔丁基）6，丙氨酸10-LHRH]的治疗，以确定由此产生的内分泌变化是否能解释使用该药物治疗期间出现的临床反应。4周后，血清促性腺激素水平低于治疗前水平的10%，而血清催乳素水平未发生变化。20名患者中有19名血清睾酮水平显著下降；这种下降与血清雌二醇水平下降22%相关。血清雄烯二酮水平也下降，但血清雌酮和硫酸脱氢表雄酮（DHAS）水平未下降。血清DHAS水平未下降表明雄激素水平的变化是卵巢分泌减少的结果，而雌二醇水平降低是前体（即睾酮）可用性降低的结果。绝经后卵巢雄激素分泌持续依赖促性腺激素刺激可能解释了一些患者对LHRH激动剂和其他一些作用方式未知或不确定的治疗药物的反应。
