The effects of low and high dose medroxyprogesterone acetate on sex steroids and sex hormone binding globulin in postmenopausal breast cancer patients

Abstract

Summary The possibility that medroxypregesterone acetate (MPA) is clinically effective at least in part by its suppression of adrenal steroidogenesis and a resultant reduction of circulating oestrogen levels was investigated in 49 postmenopausal patients with advanced breast cancer. Thirty-one patients were treated with low dose MPA (100mg three times daily) and 16 patients with high dose MPA (250mg four times daily). Plasma levels of androstenedione, testosterone, oestrone and oestradiol were all significantly reduced during treatment, with the suppression being most marked for the 17fl hydroxysteroids, testosterone and oestradiol. The fall in oestradiol levels was to about 50% of pretreatment levels, but a concomitant fall in SHBG levels to less than 25% of baseline probably resulted in the fall in free, biologically active oestradiol being only to about 70-80% of pretreatment. It is unlikely that this is a major determinant of the activity of MPA in breast cancer.

Endocrine Treatment of Breast Cancer in Women

“…Dowsett et al (115) reported that administration of either low dose (300 mg/day orally) or high dose (1000 mg I/day orally) medroxyprogesterone acetate (MPA) to postmenopausal patients with advanced breast cancer caused a significant reduction in the circulating levels of dehydroepiandrosterone sulfate, androstenedione, testosterone, estrone, and estradiol. Since, however, the treatment also induced a marked fall in sex hormone binding globulin levels, the authors speculated that the fall in biologically active free estradiol was probably only modest and unable to account for a major part of the antitumor action of MPA.…”

Progestins in Breast Cancer Treatment: A Reveiw

“…The two progestins, MPA and MA, were found to induce closely similar reduction of the androgen in one study (56), but a significantly lower serum level of androstenedione was found during MPA treatment compared to MA treatment in another study (62). Estradiol ( E,) and estrone (E, ) both decreased by about 30% during progestin treatment (52,(55)(56)(57)59). No significant difference between the two progestins was observed with regard to influence on serum levels of E, (62,63), and a significant difference in E, was found in one study (63), but not in another (62).…”

“…About 1/3 of the precursor androgens are produced in the ovaries (34), the rest in the adrenal glands (33). Serum levels of androgens are reduced to about 60% of basal levels during progestin treatment (52,(55)(56)(57)(58)(59), due to progestin action on the hypothalamic-pituitary-adrenal axis (56,58). Only one study reports an increased androgen catabolism (60), but this is probably of less clinical importance due to the minor influence of oral high-dose progestin treatment on drug catabolism by the mixed function oxidase system (61).…”

Mammary steroid metabolizing enzymes in relation to hyperplasia and tumorigenesis in the dog

“…Another explanation for the high dose progestin-induced inhibition of tumour progression is the fact that many synthetic progestins used for breast cancer treatment have intrinsic androgenic and glucocorticoid activities [42,43]. Due to this glucocorticoid activity progestin treatment results in suppression of plasma cortisol concentrations in humans [44,45], dogs [46][47][48] and cats [49,50] and reduces the plasma concentrations of sex steroids in postmenopausal breast cancer patients [51][52][53]. In vitro progestins inhibit the biosynthesis of DHP and estradiol in rat granulosa cells [54,55] and of estradiol in breast cancer cell lines [56].…”