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PubMed1987

The effects of cyproterone acetate on statural growth in children with precocious puberty.

Forty-four patients (42 f, 2 m) with precocious puberty (31 idiopathic, 1 familial, 7 cerebral, 5 McCune-Albright) were treated with cyproterone acetate for periods of 1-8.75 years in different (P less than 0.05) daily dosages of 117 +/- 6.1 mg/m2 per day (mean +/- SEM, group A, N = 20) and 60.8 +/- 2.42 mg/m2 per day (group B, N = 24). Thirty-three girls had experienced menarche before therapy at a mean age of 4.89 +/- 0.42 years. Treatment was started at a chronologic age of 5.45 +/- 0.33 years in the girls and 5.74 +/- 1.34 years in the boys. At the time of evaluation, 31 of our patients had reached final height. With respect to the effects of treatment on statural growth, the Standard Deviation Scores were retrospectively determined for height, weight, and growth velocity. The initial Bayley-Pinneau height predictions were compared with final height and target height, and the skeletal maturation was studied. There were no significant differences between those parameters in the patients of group A and B or between treated and untreated subjects as far as final height and target height were concerned. It is concluded that cyproterone acetate administered orally at daily doses from 50-150 mg/m2 does not improve statural growth of patients with precocious puberty.

Body Height↗
PubMed1991

Androstanediolglucuronide: a parameter for peripheral androgen activity before and during therapy with cyproterone acetate.

Serum 5 alpha-androstane-3 alpha,17 beta-diolglucuronide (3 alpha-AdiolG) levels were measured and the degree of hirsutism was scored in female outpatients complaining of excessive hair growth before and during treatment with cyproterone acetate. In a group of 16 patients with idiopathic hirsutism and in a group of 9 patients with either polycystic ovary syndrome and hirsutism or 21-hydroxylase deficiency and hirsutism, the serum 3 alpha-AdiolG levels were significantly increased (p less than 0.01) as compared with the serum 3 alpha-AdiolG level in a control group of 13 apparently healthy women: 3 alpha-AdiolG levels, median (range), being 5.3 (2.3-7.8) nmol/l, 8.5 (4.1-10.4) nmol/l, and 2.9 (1.5-5.2) nmol/l, respectively. In contrast to a previous report, no correlation was found between the serum 3 alpha-AdiolG levels and the Quetelet Index (N = 18, R = 0.42, p greater than 0.05), indicating an apparent ineffectiveness of the excessive androgen turnover in fat tissue. The use of the anti-androgen drug cyproterone acetate alone or in combination with ethinylestradiol in reverse sequential therapy did lower the 3 alpha-AdiolG levels significantly (p less than 0.01) together with a significant decrease (p less than 0.01) in hirsutism score. From the results of this study we therefore conclude that 3 alpha-AdiolG can be used as a parameter for peripheral androgen action before and during treatment with anti-androgens.

Androgen Antagonists↗
PubMed1982

Orchiectomy combined with cyproterone acetate or prednisone in the treatment of advanced prostatic carcinoma. A randomized clinical and endocrine study.

Thirty-four previously untreated patients with advanced prostatic carcinoma, histologically graded as being of intermediate differentiation, were randomized in three groups. All patients were treated with primary orchiectomy, group I was observed without additional therapy, group II treated with oral administration of prednisone and group III treated with cyproterone acetate per os. The clinical results with the combination orchiectomy and prednisone was encouraging both when initial and secondary remissions were considered. Cyproterone acetate treatment induced a highly significant raise in plasma prolactin, a fact which may explain the less favourable clinical results in this group.

Adenocarcinoma↗
PubMed1981

The effect of cyproterone acetate on the mouse adenohypophysis. II. Gonadotrophs and somatotrophs.

The adenohypophyses of adult male C57BL/6J mice pituitaries injected with cyproterone acetate for four weeks were examined with the electron microscope. The gonadotrophs showed an accumulation of the hormone-containing granules, and a noticeable decrease in the amount of rough endoplasmic reticulum. The somatotrophs exhibited proliferated profiles of rough endoplasmic reticulum, hypertrophied Golgi apparatus, and a slight decrease in the GH-containing granules. It is believed that the cyproterone acetate may have inhibited synthesis and release of the gonadotropins, and may have stimulated the GH -producing cells through the progestational activity of this antiandrogen.

Animals↗
PubMed1990

[Cancers of the prostate and cyproterone acetate. Value of blood testosterone and PSA levels for treatment surveillance].

On the basis of a retrospective series of 74 patients with adenocarcinoma of the prostate, the authors study the survival of these patients according to the clinical stage of the lesion when treated with cyproterone acetate. Biologically speaking, the authors have studied the evolution of the blood testosterone level, as well as of PSA and PAPs. Their conclusion is that the PSA is an excellent indicator of the efficacy of the cyproterone acetate treatment. Its fast decrease proves treatment efficacy, while a new rise indicates the resumption of evolution of the neoplastic process and must lead to change the therapeutic approach.

Adenocarcinoma↗
PubMed1991

[Cyproterone acetate in the treatment of girls with central precocious puberty].

Cyproterone acetate (Androcur, Schering Co) was administered within the range of recommended doses to seven girls with central premature puberty. During the investigation period, on average within 1.8 years, in all girls regression of the premature development of sex signs and gonads occurred, as well as normalization of the vaginal cytology. The growth rate corresponded to that of girls of similar calendar age, while there was progress of bone maturation. The growth prognosis deteriorated on average by 3.7 cm per year, during the whole investigation period by as much as 5.1 cm. Cyproterone acetate did not meet the demands of adequate comprehensive treatment of children with central premature puberty.

Androgen Antagonists↗
PubMed1990

[Anti-androgen treatment of hirsutism with cyproterone acetate].

22 female patients suffering from idiopathic hirsutism were treated according to Hammerstein's reversed sequential scheme over 12 months. During each treatment cycle of 21 days, the daily medication consisted of 1 coated tablet containing 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate (Diane-35); in addition, the patients received one i.m. injection of 300 mg cyproterone acetate (Androcur-Depot) on the first day of each cycle. This therapy resulted in improvement of the disease in 19 of our patients (86.4%). The transitory, mild side effects observed did not require interruption of the treatment. The reversed sequential scheme making use of the depot form of CPA can successfully be administered in patients with hirsutism.

Administration, Oral↗
PubMed1988

Effects of castration and antiandrogens (RU 23908 and cyproterone acetate) on glandulain activity and on the secretory epithelium of the rat submandibular gland.

1. The influence of hormones on the submandibular gland of rodents has attracted more attention since the observation of the sexual dimorphism of these organs. Androgens enhance both the development and the secretory activity of the gland. 2. In the present investigation we have studied the differences in wet weight, protein content, glandulain activity and morphometry of granular convoluted tubules of submandibular glands excised from control, castrated and antiandrogen-treated (RU 23908 or cyproterone acetate) male adult albino rats. 3. Castration and antiandrogenic treatment did not affect the wet weight or protein content of the organs. Castration or treatment with RU 23908, but not treatment with cyproterone acetate, decreased glandulain activity and the height of the secretory epithelium of granular ducts. 4. The morphology and glandulain activity of submandibular gland granular ducts do not seem to be related solely to plasma testosterone concentration. Different hormonal treatments are needed to identify other factors implicated in the phenomenon.

Aminopeptidases↗
PubMed1985

[Therapy of virginal prostatic cancer with cyproterone acetate].

52 patients with virginal carcinoma of the prostate were treated with 100 mg cyproterone acetate during an observation period of 12 to 68 months (average 38.2 months). In 7 patients (13.5%) the therapy had to be stopped because of gastrointestinal intolerability. Of 45 patients in whom a relevant clinical statement was possible 44.4% showed a progression of the disease after a period of 3 to 30 months (on average 10.8 months). 95% of these patients had carcinomas with a higher degree of malignity (GII or GIII). From this is concluded that the monotherapy of the medium- to undifferentiated carcinoma of the prostate with cyproterone acetate is to be refused in this dosage.

Aged↗
PubMed1982

[Effect of cyproterone acetate on the 3 alpha-hydroxysteroid-dehydrogenase activity of cutaneous fibroblasts in culture].

In men, parallel variations in urinary 3 alpha 5 alpha androstane 17 beta diol with the amount of sex skin fibroblast DHT receptors rise the question of a relationship of 3 ketosteroid reductase activity and specific DHT binding. To test this hypothesis, we measured 3 alpha 5 alpha androstane 17 beta diol biosynthesis in cultured sex skin fibroblasts, in the presence of high amounts of cyproterone acetate which competes with DHT for its receptor: when 95% of DHT is displaced by cyproterone acetate, the 3 keto steroid reductase activity remains unchanged. These results suggest that the relationship of 3-keto-steroid reductase activity and androgen receptors is unlikely.

Animals↗
PubMed1983

[Effects of antiandrogenic treatment with cyproterone acetate on the sexual tonus in virilized women].

Sexual responsiveness was assessed in 46 virilized women during cyproterone acetate treatment over a period of several years according to a sexual score previously described. In general, sexual tonus was depressed by intensive cyproterone acetate medication of several months' duration without concurrent oestrogen. By changing to sequential therapy according to Hammerstein, however, sexual tonus returned to initial levels in the group with normal pre-medication responsiveness. Furthermore, in another group with diminished sexual tonus before treatment, sexual responsiveness, in particular the capacity for orgasm, was stimulated to the level of the first group. The endocrinological basis for this observation is discussed with aid of results of the plasma testosterone/sex hormone binding globulin complex.

Adult↗
PubMed1980

Pubertal development in girls with sexual precocity after discontinuation of treatment with cyproterone acetate.

Twenty-four girls with sexual precocity who had been treated with cyproterone acetate were followed for periods from 1 to 8 1/2 years after the discontinuation of therapy. It was found that their further pubertal development and the resumption or appearance of menstruation followed a natural course within the wide limits of physiological variability. It is concluded that puberty resumes its natural course following cessation of treatment with cyproterone acetate, and it is assumed that the reproductive ability of these patients will not be affected.

Adolescent↗
PubMed1981

[Effects of cyproterone acetate on cardiovascular risk factors in patients with carcinoma of the prostate (author's transl)].

15 patients with advanced carcinoma of the prostate were studied in a prospective trial during treatment with 200 mg cyproterone acetate daily by mouth. Changes in variables (salt-water balance, antithrombin III, fibrinolytic activity, plasma lipoproteins) known to influence the risk of cardiovascular complications were recorded during the initial two months. Blood and plasma volume were unchanged, whereas the 24 h urine volume and the urinary sodium excretion were transitory increased. The body weight was decreased. The antithrombin III concentration and the fibrinolytic activity were increased. The lipoprotein fractions HDL and LDL and the HDL/LDL quotient decreased. The recorded changes of cardiovascular risk factors indicate that the risk of water retention and thereby congestive heart failure is not increased during cyproterone acetate treatment. The risk for thrombembolic disease is rather decreased. The small changes in lipoprotein fractions can hardly affect the incidence of cardiovascular disease in elderly men with prostatic carcinoma.

Aged↗
PubMed1985

Cyproterone acetate in the treatment of metastatic cancer of the male breast.

Ten male patients with advanced cancer of the breast were treated with cyproterone acetate, an anti-androgenic compound with additional progestational properties. Seven patients achieved a response, for a median duration of 8 months. Plasma testosterone and estradiol levels fell significantly during therapy, but quantitatively this drop was not related to the therapeutic response. Cyproterone acetate is an effective and well-tolerated treatment for metastatic male breast cancer.

Aged↗
PubMed1993

Luteinizing hormone-releasing hormone agonists in prostate cancer. Elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol.

BACKGROUND: In response to the first administration of a luteinizing hormone-releasing hormone (LHRH) agonist, the secretion of pituitary gonadotropin increases sharply and gives rise to a transient surge in the concentration of serum testosterone. This effect reaches a peak 4 to 7 days after the start of therapy and results in the onset of clinical symptoms and signs of tumor flare in 5% to 10% of patients. METHODS: To determine whether the effects of the LHRH-induced flare reaction are preventable, cyproterone acetate (100 mg) and low-dose diethylstilbestrol (0.1 mg) were administered daily for 4 weeks to inhibit the pituitary before the initiation of therapy with a depot LHRH agonist, goserelin acetate (3.6 mg every 4 weeks). Diethylstilbestrol was stopped after 8 weeks to eliminate associated minor toxicity while administration of cyproterone acetate was continued to suppress vasomotor symptoms. Twenty-four men with histologically confirmed prostate cancer were enrolled in the study: 6 with Stage C, 2 with Stage D1, and 16 with Stage D2 disease. RESULTS: Lead-in therapy reduced the concentration of serum testosterone into the castrate range within 1 week, and no significant change was observed in the mean level after administration of goserelin acetate. Neither was there an effect on the initial rate of normalization of serum prostate specific antigen (PSA); normal PSA values were obtained in 50% of patients after 10 weeks and in 70% after 32 weeks. In the subgroup of patients with Stage D2 disease, longer median survival was predicted by a normal serum PSA, either stable or decreasing, after 32 weeks of treatment. The regimen was well tolerated with a low incidence of hot flushes. CONCLUSIONS: These results imply that in the absence of LHRH-induced tumor flare, prognosis is related to the ability of therapy to maintain a PSA nadir in the normal range.

Acid Phosphatase↗
PubMed1993

Short-term versus long-term addition of cyproterone acetate to buserelin therapy in comparison with orchidectomy in the treatment of metastatic prostate cancer. European Organization for Research and Treatment of Cancer--Genitourinary Group.

In an open, multicenter, three-armed, randomized study, we compared the effects of short-term (2 weeks) and continuous addition of the antiandrogen cyproterone acetate to the luteinizing hormone-releasing hormone agonist buserelin to those of orchidectomy in patients with advanced prostate cancer. No significant differences among the three treatment arms with respect to response rate, subjective response, time-to-progression, overall survival, and cancer deaths were observed. It was concluded that the short-term or continuous addition of cyproterone acetate to buserelin administered intranasally did not improve treatment results compared to orchidectomy only.

Adult↗
PubMed1976

Fine structure of the testis and epididymis of rats treated with cyproterone acetate.

Adult male rats were administered the antiandrogen, cyproterone acetate, for 4, 8 or 12 weeks, and the histology and fine structure of the testis and several parts of the epididymis were studied. After treatment for 8 or 12 weeks, the testes of treated animals displayed a great reduction in the abundance of late spermatids. Necrotic cells, many of which were identified as cap-phase spermatids, were present in the seminiferous epithelium. Sertoli cells contained many large lipid droplets and lysosome-like structures with a content of cellular debris, including parts of spermatids. Leydig cells of treated rats were smaller than those of control animals at all the intervals studied. Sperm were absent from the lumen of the middle segment, or caput epididymidis, of severely affected specimens. In the terminal segment, or cauda epididymidis, the microscopic appearance varied in different regions. In the proximal part of the cauda epididymidis, the lumen was usually clear of sperm. The epithelium was tall and the light cells were very large and distended with many dense bodies resembling lysosomes. In contrast, in the distal part of the cauda epididymidis, the lumen was filled with sperm and debris, which appeared to be derived from germ cells. It is suggested that the light cells of the epididymal epithelium may have a role in clearing the lumen in the proximal part of the cauda epididymidis, in which they are particularly large and numerous. The results suggest that in the presence of cyproterone acetate, germ cells develop up to a cap-phase spermatids and then begin to undergo degeneration and death. This alteration may have an important role in the antifertility effect of the drug, but changes in the epididymis may contribute also.

Animals↗