Androgens in postmenopausal breast cancer: Excretion, production and interaction with estrogens

The role of androgens and estrogens has been investigated in postmenopausal breast cancer patients. No differences were found in the urinary excretion of estrone and of estriol between 41 primary mammary cancer patients and 48 normal postmenopausal women, representative of the normal population. A significantly lower excretion of androgen metabolites (11-DOKS) was found in the patients. Because 11-DOKS in postmenopausal women arise mainly from three secretory products and estrogens are mainly derived from peripheral conversion of androstenedione to estrone, production rates of DHEA, DHEAS and androstenedione and the conversion of androstenedione to estrone were estimated. No significant difference was found between the two groups for the blood production rate of androstenedione, neither for its conversion to estrone. The urinary production rate of DHEAS was definitely lower in the selected breast cancer patients compared to normal controls. The DHEA production rate was also lower but statistical significance was not achieved. On account of these results the hypothesis was tested that DHEAS, DHEA or one of their metabolites might interfere with the binding of estradiol to its specific receptor, an essential step in its mechanism of action. From the results of anin vitro incubation study of receptors from human myometrial and mammary tumour tissue with several steroids, evidence was obtained that the estradiol binding was inhibited, in a molar concentration ratio not far beyond the physiological range, by 5-androstene-3β,17β-diol, a steroid closely related to DHEA. If these in vitro findings may be applied to in vivo conditions, it is conceivable that androstenediol is a regulating agent of estrogenic action at the cellular level. Abbreviations: E1—estrone, 3-hydroxy-l,3,5(10)-estratrien-17-one; E2—estradiol, 1,3,5(10)-estratriene-3,17β-diol; E3—estriol, 1,3,5(10)-estratriene-3,16α,17β-triol; DHEA—dehydroepiandrosterone, 3β-hydroxy-5-andro-sten-17-one; DHEAS—dehydroepiandrosterone-sulfate; DHT—dihydrotestosterone, 5α-androstane-17β-ol-3-one; T—testosterone, 4-androstene-17β-ol-3-one; A—andro-stenedione, 4-androstene-3,17-dione; Adiol—5-androstene-3β,l7β-diol; 11-DOKS—11-deoxo-17-ketosteroids, etio-cholanolone + androsterone + dehydroepiandrosteron