Labrie Fernand, Cusan Leonello, Gomez José Luis, Martel Céline, Bérubé René, Bélanger Patrick, Bélanger Alain, Vandenput Liesbeth, Mellström Dan, Ohlsson Claes
Molecular Endocrinology and Oncology Research Center, Laval University Hospital Research Center (CRCHUL) 2705, Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2.
J Steroid Biochem Mol Biol. 2009 Jan;113(1-2):52-6. doi: 10.1016/j.jsbmb.2008.11.004. Epub 2008 Nov 27.
The objective of this study was comparison of circulating androgens and their metabolites as well as estrogens measured for the first time by a validated mass spectrometry technology in 60-80-year-old men and women of comparable age. Castration in men (n=34) reduces the total androgen pool by only about 60% as indicated by the decrease in the serum levels of the glucuronide metabolites of androgens compared to intact men (n=1302). Such data are in agreement with the 50 to 75% decrease in intraprostatic dihydrotestosterone (DHT) concentration after castration. Most interestingly, the same amounts of androgens and estrogens are found in postmenopausal women (n=369) and castrated men of comparable age. The most significant therapeutic implication of these findings is the absolute need to add a pure (nonsteroidal) antiandrogen to castration in men with prostate cancer in order to block the action of the 25 to 50% DHT left in the prostate after castration. Not adding an antiandrogen to castration in men treated for prostate cancer is equivalent to not prescribing a blocker of estrogens in women suffering from breast cancer because they are postmenopausal and have low circulating estradiol.
本研究的目的是比较60至80岁年龄相仿的男性和女性首次通过经过验证的质谱技术测量的循环雄激素及其代谢产物以及雌激素。与未阉割男性(n = 1302)相比,阉割男性(n = 34)后,雄激素葡糖醛酸代谢产物血清水平下降,表明雄激素总库仅减少约60%。这些数据与阉割后前列腺内二氢睾酮(DHT)浓度下降50%至75%一致。最有趣的是,在绝经后女性(n = 369)和年龄相仿的阉割男性中发现了相同量的雄激素和雌激素。这些发现最重要的治疗意义是,对于前列腺癌男性患者,在阉割治疗中绝对需要添加一种纯(非甾体)抗雄激素药物,以阻断阉割后前列腺中残留的25%至50%的DHT的作用。在前列腺癌男性患者的阉割治疗中不添加抗雄激素药物,等同于在患有乳腺癌的绝经后女性患者中不使用雌激素阻滞剂,因为她们绝经后循环雌二醇水平较低。