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  • Title: The effects of diethylstilbestrol and medroxyprogesterone acetate on kinetics and production of testosterone and dihydrotestosterone in patients with prostatic carcinoma.
    Author: Nolten WE, Sholiton LJ, Srivastava LS, Knowles HC, Werk EE.
    Journal: J Clin Endocrinol Metab; 1976 Dec; 43(6):1226-33. PubMed ID: 1002814.
    Abstract:
    Alterations in the metabolism of testosterone (T) and dihydrotestosterone (DHT) induced by diethylstilbestrol (DES) or medroxprogesterone acetate (MPA) could account for the beneficial therapeutic effect of these agents in prostatic carcinoma. To investigate this possibility we sutdied plasma kinetics of T and DHT in 17 elderly patients with prostatic carcinoma, before and after treatment with DES (1 or 5 mg/d) or MPA (10 or 30 mg/d) for 30 days. Metabolic clearance rates (MCR) were determined with the single injection technique and by use of two compartment model, plasma concentrations (PC) of T and DHT by radioimmunoassay, the per cent of T bound to plasma protein (T-binding) by charcoal adsorption of the unbound steroid. Production rate (PR) and PC of T were lower, PR and PC of DHT were higher in our patients than in normal men. With both DES regimens, PR, PC and MCR of either androgen declined; however, T was suppressed to a much greater extent than DHT. In either instance, the decrease may have been caused by direct suppression of testicular androgen synthesis and/or by decreased gonadotropin stimulation. Enhanced T-binding played an additional role in reducing the free testosterone index. High and low dose of DES were equally effective. The low dose regimen of MPA did not influence androgen metabolism. MPA in the higher dose suppressed PR and PC of T and DHT, possibly due to effects on testicular synthesis or by gonadotropin suppression as suggested for DES. In contrast to DES, MPA failed to cause profound changes in MCR of either androgen or in T-binding. When judged by its influence on the metabolism of T and DHT in prostatic carcinoma, MPA in higher doses is much less effective than either dose regimen of DES. The effects of diethylstilbestrol(DES) and medroxyprogesterone acetate (MPA) on plasma kinetics and production of testosterone(T) and dihydrotestosterone (DHT), and on plasma protein binding of T were measured in 17 patients (50-93 years of age) suffering with metastatic carcinoma of the prostate both before and during treatment for this disease. Blood samples were obtained before injection of 30 mcCi tritiated T or tritiated DHT and at 10, 15, 20, 40, 55, 70, and 90 minutes after injection. T and DHT were measured by radioimmunoassay. Metabolic clearance rates were measured as well. Production rate (PR) and plasma concentrations (PCs) of T and DHT were higher in these patients than in normal men. When DES was given, PR, PC,and metabolic clearance rates of T and DHT declined, with T suppressed to a greater extent. There was also enhanced T-binding. In patients treated with MPA, 10 mg given for 30 enhanced T-binding. In patients treated with MPA, 10 mg given for 30 days, significantly different changes were seen in the kinetics of T and DHT in 8 patients. Patients treated with 30 mg of MPA for 30 days showed suppression of PR and PC of T and DHT. MPA failed to cause profound changes in the metabolic clearance rate of either androgen or in T-binding. These results indicate that MPA is less effective than DES.
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