Androgen Production and Conversion to Estrogens in Normal Postmenopausal Women and in Selected Breast Cancer Patients

Abstract

Urinary production rates of dehydroepiandrosterone (D) and dehydroepiandrosterone sulfate (DS) by isotope dilution, and the blood production rate of androstenedione (A) by continuous infusion technique have each been measured in 8 normal postmenopausal women. Both measurements were done in a group of 6 breast cancer patients. The cancer patients were at the time of the primary operation at least 6 yr postmenopausal; at the time of the study they were at least 3 yr after the operation. All of them were in good health and free of demonstrable recurrence of the tumor.The contribution of D and DS to urinary estrogens and the conversion of A to estrone were each determined in 8 normal postmenopausal women. Both measurements were done in the 6 breast cancer patients.The mean urinary production rate of D and DS were lower in the breast cancer patients than in the normal subjects. The difference was significant (p < 0.025) for DS. In the breast cancer patients the excretion of ll-deoxo-17-oxosteroids (11-DOKS) was lower than in the normal subjects. It is highly probable that the decreased production of D and DS is the cause of the low excretion of 11-DOKS in the patients.In 6 of the 14 experiments the specific activity of D isolated from the sulfate and the glucuronide fraction was not consistent with the model of van de Wiele et al. It is likely that in these cases neither D-glucuronide nor D-sulfate could be considered a unique specific metabolite of the D-and the DS-pool respectively. The contribution of D and DS to urinary estrogens was low (less than 0.01%) in both normals and in breast cancer patients.In the normal subjects we found a mean metabolic clearance rate of A of 1843 ± 131 (SE) liter per day and a mean plasma-level of A of 0.83 ± 0.13 ng per liter leading to a daily blood production rate of 1.64 ± 0.38 mg of A. In the breast cancer patients we found a mean metabolic clearance rate of 2398 ± 4 2 5 (SE) liter per day and a mean plasma-level of A of 0.60 ± 0.12 \xg per liter leading to a daily blood production rate of 1.46 ± 0.39 (SE) mg of A.The conversion of circulating androstenedione to estrone was 2.5 ± 0.3 ( S E ) % in the normal subjects and 2.9 ± 0.2 ( S E ) % in the breast cancer patients. Both in the normal subjects and in the breast cancer patients a daily estrone production of approximately 40 M*g can therefore be accounted for by the conversion of plasma born androstenedione. (/ Clin Endocrinol Metab 37: 101, 1973)

Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients

“…It was not possible to determine pretreatment values in these patients but for comparative purposes values may be drawn from previously published studies (Poortman et al, 1973;MacDonald et al, 1978;Santen et al, 1978) which used the same methodology. These data are shown in Table IV, and are plotted in Figure 1 together with the p values from patients in the current study, and 2 patients treated with 1000mg AG from a previous study …”

The dom project for the early detection of breast cancer, Utrecht, The Netherlands

“…We had been involved in endocrinological studies at our university which had emphasized the role of extra-ovarian oestrogens in the aetiology of endometrial and breast cancer [3,4].…”

Modulatory Mechanisms of Chemical Carcinogenesis: The Role of the NADPH Pool in the Benzo(a)pyrene Activation

“…treatment with DEA inhibit the formation of spontaneous cancer in mice (24). In addition, urinary production rates of DEA and DEA sulfate are significantly reduced in breast cancer patients compared to controls (25). Premenopausal women with benign breast cancer, who are considered under risk of subsequently developing breast cancer (26), have a lower plasma level of DEA (27).…”

“…The cells used in the various experiments were subcultured from primary cultures in Dulbecco's modified Eagle's medium containing 13% calf serum, penicillin (100 U/ml), and streptomycin (100 pglml), maintained in an atmosphere of 5% COz in air at 37°C. Doubling times in our culture conditions were 25 and 96 hr for HL and HSF, respectively. No differences between normal and glucose-6-phosphate (G6P)-deficient cells with respect to growth rate and morphology were observed.…”