Institute of Doping Analysis and Sports Biochemistry Dresden, Kreischa, Germany; Molecular Cell Physiology and Endocrinology, Institute of Zoology, Technical University Dresden, Germany.
Molecular Cell Physiology and Endocrinology, Institute of Zoology, Technical University Dresden, Germany.
Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.
4-Hydroxyandrost-4-ene-3,17-dione, also named formestane, is an irreversible aromatase inhibitor and therapeutically used as anti-breast cancer medication in post-menopausal women. Currently, no therapeutical indication led to approval of its 17-hydroxylated analog 4-hydroxytestosterone, an anabolic steroid. However, it is currently investigated in a clinical trial for breast cancer. In context with sports doping, aromatase inhibitors are administered to reduce estrogenic side effects of misused anabolic substances or their metabolites. Therefore, both substances are prohibited in sports by the World Anti-Doping Agency (WADA). Analysis of urinary phase I and phase II metabolites showed similar results for both compounds. In the current investigation, 4-hydroxyandrost-4-ene-3,17-dione, 4-hydroxytestosterone and seven of their described urinary metabolites as well as 2α-hydroxyandrostenedione were tested in the yeast androgen screen and the yeast estrogen screen. Androgenic effects were observed for all tested substances, except for one, which showed anti-androgenic properties. With regard to the yeast estrogen screen, estrogenic effects were observed for only two metabolites at rather high concentrations, while six out of the ten substances tested showed anti-estrogenic properties. In terms of the strong androgenic effect observed for 4-hydroxytestosterone (10 M), 4-hydroxyandrost-4-ene-3,17-dione (10 M) and two more urinary metabolites, the yeast androgen assay may also be used to trace abuse in urine samples.
4-羟基雄甾-4-烯-3,17-二酮，也称为 Formestane，是一种不可逆的芳香酶抑制剂，临床上被用作绝经后妇女的抗乳腺癌药物。目前，没有治疗适应症导致其 17-羟化类似物 4-羟基睾酮（一种合成代谢类固醇）获得批准。然而，它目前正在乳腺癌的临床试验中进行研究。在运动兴奋剂方面，芳香酶抑制剂被用于减少滥用的合成代谢物质或其代谢物的雌激素副作用。因此，世界反兴奋剂机构（WADA）将这两种物质都禁止在运动中使用。对尿液 I 相和 II 相代谢物的分析表明，这两种化合物的结果相似。在当前的研究中，4-羟基雄甾-4-烯-3,17-二酮、4-羟基睾酮及其描述的七种尿液代谢物以及 2α-羟基雄烯二酮在酵母雄激素筛选和酵母雌激素筛选中进行了测试。除一种具有抗雄激素特性外，所有测试物质均显示出雄激素作用。关于酵母雌激素筛选，只有两种代谢物在相当高的浓度下显示出雌激素作用，而十种测试物质中有六种表现出抗雌激素作用。鉴于 4-羟基睾酮（10µM）、4-羟基雄甾-4-烯-3,17-二酮（10µM）和另外两种尿液代谢物观察到的强烈雄激素作用，酵母雄激素测定法也可用于追踪尿液样本中的滥用情况。
