Blossey H C, Wander H E, Koebberling J, Nagel G A
Cancer. 1984 Sep 15;54(6 Suppl):1208-15. doi: 10.1002/1097-0142(19840915)54:1+<1208::aid-cncr2820541319>3.0.co;2-k.
Postmenopausal patients with metastatic breast cancer were treated with medroxyprogesterone acetate (MPA) (Clinovir) in dosages between 500 and 1500 mg orally per day. The relation of MPA plasma concentrations and endocrine effects were studied in a longitudinal fashion. MPA exerted suppressive effects on the basal and gonadotropin-releasing hormone (GnRH) stimulated gonadotropin secretion, cortisol, dehydroepiandrosterone (DHEA), and estradiol (E2) in a dose-dependent manner leading to a complete suppression with 1500 mg orally per day. The depression of thyroid hormones (T3 and T4) coincided with a depression of the thyroxine-binding index (TBI). MPA did not affect human growth hormone (hGH), basal and thyrotropin-releasing hormone (TRH) stimulated thyroid-stimulating hormone (TSH) and aldosterone. Basal and TRH-stimulated prolactin (PRL) secretion showed a slight but distinct elevation. From these data it is concluded that in postmenopausal patients MPA exerts its antitumor activity by an interference with the hypothalamo-pituitary adrenal axis in the sense of a selective pharmacologic hypophysectomy leading to complete suppression of adrenal steroid secretion. Additionally, MPA inhibits tumor cell growth through the progesterone receptor. A dual mechanism for the antitumor activity of high dose is postulated MPA: ablative through suppression of the hypothalamo-pituitary-adrenal axis and subsequent estrogen deprivation, and additive via the progesterone receptor directly on the tumor cell. The significance of gonadotropin suppression in the postmenopause for breast cancer growth is unclear. The depression of T3 and T4 is due to a depression of thyroid hormone-binding proteins. The elevation of PRL secretion may be explained by a slight estrogenic activity of MPA metabolites.
绝经后转移性乳腺癌患者接受醋酸甲羟孕酮（MPA，商品名Clinovir）治疗，口服剂量为每日500至1500毫克。以纵向方式研究了MPA血浆浓度与内分泌效应之间的关系。MPA对基础促性腺激素和促性腺激素释放激素（GnRH）刺激的促性腺激素分泌、皮质醇、脱氢表雄酮（DHEA）和雌二醇（E2）具有剂量依赖性抑制作用，每日口服1500毫克时可导致完全抑制。甲状腺激素（T3和T4）的降低与甲状腺素结合指数（TBI）的降低同时出现。MPA不影响人生长激素（hGH）、基础促甲状腺激素和促甲状腺激素释放激素（TRH）刺激的促甲状腺激素（TSH）以及醛固酮。基础和TRH刺激的催乳素（PRL）分泌有轻微但明显的升高。从这些数据得出结论，在绝经后患者中，MPA通过干扰下丘脑 - 垂体 - 肾上腺轴发挥其抗肿瘤活性，从选择性药物垂体切除的意义上来说，导致肾上腺类固醇分泌完全抑制。此外，MPA通过孕酮受体抑制肿瘤细胞生长。推测高剂量MPA的抗肿瘤活性有双重机制：通过抑制下丘脑 - 垂体 - 肾上腺轴和随后的雌激素剥夺产生消融作用，以及通过孕酮受体直接作用于肿瘤细胞产生相加作用。绝经后促性腺激素抑制对乳腺癌生长的意义尚不清楚。T3和T4的降低是由于甲状腺激素结合蛋白的降低。PRL分泌的升高可能由MPA代谢产物的轻微雌激素活性来解释。
