fosfestrol and Prostatic-Hyperplasia

Following the intravenous drip infusion of diethylstilbestrol diphosphate (DES-DP), the diethylstilbestrol (DES) concentrations both in plasma and prostatic tissue obtained from patients with prostatic carcinoma were measured by radioimmunoassay and the effects of DES on the activity of 5 alpha-reductase in the prostate obtained from BPH patients were determined in vitro. Further, the changes in the activity of 5 alpha-reductase in the prostate from the BPH patients who received DES-DP infusion were also determined. The plasma and prostatic tissue concentrations of DES rapidly declined from 2.3 micrograms/ml and 1.6 micrograms/g wet weight 1 h after DES-DP infusion to 0.8 microgram/ml and 0.25 microgram/g wet weight 3 h after DES-DP infusion, respectively, and decreased gradually thereafter until 24 h. In in vitro study progressed by BPH specimens, the 5 alpha-reduction rate was completely inhibited by an addition of 5 x 10(-4) M of DES and the DES concentration on the inhibition rate of 50% was 4 x 10(-5) M. In in vivo study, the mean production rate of 5 alpha-dihydrotestosterone (DHT) in the control specimens of BPH without infusion of DES-DP was 14.0 +/- 3.4 nmol/15 min/mg protein and the production rate of DHT in the DES-DP infused specimens of BPH was 14.7 nmol/15 min/mg protein at 3 h and 15.2 nmol/15 min/mg protein at 12 h after the termination of DES-DP infusion. These results indicated that intravenously administered DES-DP did not act via the inhibition of 5 alpha-reductase in the prostatic cells for producing the clinical effects.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Diethylstilbestrol; Dihydrotestosterone; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Time Factors

23 patients with prostatic cancer were treated with (Estracyt) estramustine phosphate disodium, (Hexron) hexestrol, and (Honvah) diethylstilbestrol 4, 4-diphosphoric ester. 16 cases were given 560-840 mg of Estracyt, 6 cases 30 mg of Hexron, and 1 case 200 mg of Honvan orally daily. Fasting serum lipids and lipoproteins fractions were measured before and during this treatment with these drugs. The results were as follows. 1) In the 1-2 months of Estracyt administration a decrease of (TC) total cholesterol and extreme increase of (TG) triglycerides were confirmed. 2) In those 5 cases where 840 mg of Estracyt/day was given, almost no difference was observed in their TC, (NEFA) free fatty acids, or (PL) phospholipid values. 3) Cardiovascular complications although not serious, were found in 2 cases of the group receiving Estracyt. With these 2 cases, their beta+pre-beta/alpha lipoprotein fraction ratio decline was either very gradual or rather turned to increase markedly despite the extreme rise of their TG values. 4) The serum lipid values in the group receiving Hexron did not show any obvious changes in TG. These values did not change much in the first 5-6 months but an increase was seen between 7-9 months. Lipoprotein fractions were similar to those in the Estracyt group. 5) With those receiving Honvan, TG values began to rise 2-4 weeks following administration. In view of the above results, the coronary risk factors which are a consequence of Estracyt, Honvan, or Hexron ingestion for treatment of prostatic cancer must be taken very seriously and must be closely monitored. (Authors' modified)

Topics: Aged; Diethylstilbestrol; Estramustine; Hexestrol; Humans; Lipids; Lipoproteins; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Hyperplasia; Prostatic Neoplasms