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 ± 0.12μg 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 (SE)% in the normal subjects and 2.9 ± 0.2 (SE)% in the breast cancer patients. Both in the normal subjects and in the breast cancer patients a daily estrone production of approximately 40 μg can therefore be accounted for by the conversion of plasma born androstenedione. (J Clin Endocrinol Metab37: 101, 1973)