fosfestrol and Body-Weight

The neonatal estrogen induces morphological changes in accessory sex organs. We have reported that papillary proliferation in prostates and squamous metaplasia of the epithelium in seminal vesicle occurred and inflammatory cells have emigrated to the lumen through the stroma and the epithelium of organs from neonatal mice treated with beta-estradiol 17-cypionate. In this study, we observed the different effect between neonatal DES and DES-dp on morphological changes in accessory sex organs of mice. After 25 weeks, neonatal estrogen injections induced the infiltration of inflammatory cells in the ventral prostate and squamous metaplasia in the epithelium of seminal vesicles. It was observed that the inflammatory cells have already infiltrated into prostates from DES-dp injected mice after 5 weeks. But DES did not cause the changes in prostates. DES induced organs from a half of mice to involute and inflammatory cell to infiltrate into the epithelium. But these were not seen in organs from another half of mice. DES-dp occurred similar effect of beta-estradiol 17-cypionate on the male accessory sex organs. It remained to be seen whether DES could have estrogen action on accessory sex organ.

Topics: Animals; Animals, Newborn; Body Weight; Diethylstilbestrol; Estrogens, Non-Steroidal; Male; Mice; Mice, Inbred Strains; Prostate; Seminal Vesicles

Since the introduction of hormonal treatment for prostatic cancer by Huggins and Hodges in 1941, severe side effects of synthetic estrogen, which have overcome its benefit, have been reported in the U.S.A. and in European countries. However, in Japan the adverse effects of estrogen have been reported to be milder than in western countries, and estrogen still has an important role in the treatment of prostatic cancer in Japan. In this communication, the side-effects of synthetic estrogen administered to 109 prostatic cancer patients, who were admitted to Kyoto University Hospital between 1980-1990 are reported. Fifty-three (48.6%) of the 109 patients suffered adverse side effects of the estrogen, specifically cardiac disease (20.2%), fluid retention (14.7%) and hypertension (13.8%). Five of these patients died. Among the risk factors analyzed, daily dose, past history of cardio-vascular disease and ECG abnormalities were significantly correlated with the appearance of adverse effects. The reasons why the frequency of lethal side-effects is lower in our cases compared to findings reported by the Veterans Administration group may be the lower daily dose and cessation of estrogen administration when mild adverse effects appear and some other unknown factors, although the background of the patients and method of analysis are not comparable among them. The overall frequency of side-effects in prostatic cancer patients administered estrogen in our cases is not necessarily lower than in western countries, but the severity of the side effects was milder in our cases. We must be a ware of the potential adverse effects of estrogen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Blood Pressure; Blood Urea Nitrogen; Body Weight; Diethylstilbestrol; Drug Administration Schedule; Electrocardiography; Estrogens; Heart; Hormones; Humans; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Risk Factors

Clinical trials have utilized intermittent diethylstilbestrol diphosphate (DES) therapy in advanced symptomatic prostatic carcinoma to diminish the morbidity of standard endocrine therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic adenocarcinoma 60 days following tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum testosterone returned toward control levels (1.0 ng/ml). Initial mean tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in tumor doubling time was achieved only by rats receiving castration or high dose DES. Intermittent DES administration controls tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to castration.

Topics: Animals; Antineoplastic Agents; Body Weight; Diethylstilbestrol; Drug Administration Schedule; Male; Orchiectomy; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone