<unk>  and its side effects have been evaluated for the treatment of advanced prostate cancer in a phase III international multicenter randomized controlled trial headed by Jacobi and colleagues of the Department of Urology, University of Mainz. The study consisted of 191 patients from 12 treatment centers, who were treated for 6 months with intramuscular injections of either 100 mg/month<unk>  (96 men) or 300 mg/week cyproterone acetate (95 men). Findings for a subgroup of 42 men at the University of Mainz center were initially reported in 1978 and 1980. These men were age 51 to 84 years (mean 68 years), and men with pre-existing cardiovascular disease were excluded. A considerable incidence of cardiovascular complications was reported for the<unk>  group (76%; 16/21 incidence total); there was a 67% (14/21) incidence of cardiovascular morbidity and a 9.5% (2/21) incidence of cardiovascular mortality. The cardiovascular morbidity in this group included peripheral edema and superficial thrombophlebitis (38%; 8/21), coronary heart disease (24%; 5/21), and a deep vein thrombosis (4.8%; 1/21), while the cardiovascular mortality included a myocardial infarction (4.8%; 1/21) and a pulmonary embolism (4.8%; 1/21). Eight of the cases of cardiovascular complications in the<unk>  group, including the two deaths, were regarded as "severe". Conversely, no incidence of cardiovascular toxicity occurred in the cyproterone acetate comparison group (0%; 0/21). Other side effects of<unk>  included gynecomastia (100%; 21/21) and erectile dysfunction (90%; 19/21). The cardiovascular complications with<unk>  in this relatively small study are in contrast to large and high-quality clinical studies of high-dose polyestradiol phosphate and transdermal estradiol for prostate cancer, in which minimal to no cardiovascular toxicity has been observed. An expanded report of 191 patients, which included the 42 patients from the University of Mainz center plus an additional 149 patients from 11 other centers, was published in 1982. The antitumor effectiveness of<unk>  and cyproterone acetate in this study was equivalent. The rates of improvement, no response, and deterioration were 52%, 41%, and 7% in the<unk>  group and 48%, 44%, and 8% in the cyproterone acetate group, respectively. However, the incidence of a selection of specific side effects, including gynecomastia, breast tenderness, and edema, was significantly lower in the cyproterone acetate group than in the<unk>  group (37% vs. 94%, respectively). Gynecomastia specifically occurred in 13% (12/96) of the patients in the cyproterone acetate group and 77% (73/95) of the patients in the<unk>  group. Erectile dysfunction occurred in "essentially all" patients in both groups. Leg edema occurred in 18% (17/95) of the<unk>  group and 4.2% (4/96) of the cyproterone acetate group, while the incidences of superficial thrombophlebitis and coronary heart disease both were not described. The incidence of thrombosis was 4.2% (4/95) in the<unk>  group and 5.3% (5/96) in the cyproterone acetate group. There were five deaths in total, three in the<unk>  group and two in the cyproterone acetate group. Two of the deaths in each of the treatment groups were due to cardiovascular events, while the remaining death in the<unk>  group was due to unknown causes. The similar rate of cardiovascular complications besides edema between<unk>  and cyproterone acetate that was observed is in contrast to the initial 42-patient report and to findings with other estrogens, such as diethylstilbestrol and estramustine phosphate, which have been shown to possess significantly higher cardiovascular toxicity than cyproterone acetate. On the basis of the expanded study, the researchers concluded that cyproterone acetate was an "acceptable alternative" to estrogen therapy with<unk> , but with a "considerably more favorable" side-effect profile. After the completion of the initial expanded study, a 5-year extension trial primarily of the Ruhr University Bochum center subgroup, led by Tunn and colleagues, was conducted. In this study, the cyproterone acetate group was changed from intramuscular injections to 100 mg/day oral cyproterone acetate. Of the 39 patients in the study, the global 5-year survival rate was not significantly different between the<unk>  and cyproterone acetate groups (24% and 26%, respectively). In patients without metastases, the 5-year survival rate was 51% in the cyproterone acetate group relative to 43% in the<unk>  group, although the difference was not statistically significant. In terms of non-prostate cancer deaths, there were 5 in the CPA group and 6 in the EU group. The incidence of cardiovascular-related mortality was 3 deaths in the CPA group and 3 deaths in the EU group. Side effects during therapy with massive doses of<unk>  in women with advanced breast cancer have included appetite loss, nausea, vomiting, vaginal bleeding, vaginal discharge, nipple pigmentation, breast pain, rash, urinary incontinence, edema, drowsiness, hypercalcemia, and local injection-site reactions. Like other estrogens,<unk>  has been found to produce testicular abnormalities and disturbances of spermatogenesis in men.
Estradiol undecylate
Estradiol dienantate
Estradiol enantate
Estradiol furoate
Estradiol valerate
Estradiol hemisuccinate
Estradiol diundecylenate
Estradiol dipropionate