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 (GnRkI) 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-pituitaryadrenal 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 TJ and Tq 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.Cancer 54:1208-1215, 1984.HE SYNTHETIC PROGESTIN 1 7a-acetoxy-6a-methyl-T 4-pregnene-3,20-dione (medroxyprogesterone acetate, MPA) (Provera; Upjohn, Kalamazoo, MI; Clinovir; Upjohn, Heppenheim, FRG) is an effective drug in the hormonal therapy of breast cancer. One of the characteristic features of this drug is that its antitumor activity shows two levels of therapeutic efficiency: the response rates with low or moderate dosages were reported to be approximately 2596,' whereas with high dosages response rates of 40% and more were observed. ',* The mechanism of the antitumor activity is not known. The dose-related difference in the therapeutic efficiency suggests that MPA may act through two mechanisms, and that one of them is related to the high d~s a g e .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.