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PubMed1990

Ovulation inhibitors containing cyproterone acetate or desogestrel in the treatment of hyperandrogenic symptoms.

An open, randomized, multicenter study was carried out to compare two oral contraceptives as regards their therapeutic efficacy in androgenization symptoms such as acne, seborrhea and hirsutism in women. The preparations used were the combination of 2 mg cyproterone acetate (CPA) with 0.035 mg ethinyl estradiol (EE) (Diane 35, Schering AG, Berlin-West) and 0.150 mg desogestrel (DG) with 0.03 mg ethinyl estradiol (Marvelon, Organon, Oss, The Netherlands). The duration of therapy was 9 months. The combination of CPA-EE was used by 83 patients for 658 cycles and the combination of DG-EE by 79 women for 618 cycles. No pregnancy occurred under either therapy. Both preparations are well tolerated. However, some side-effects, such as reduced libido, nervousness and breast tenderness, were observed more frequently (p less than 0.05) in the DG-EE group than among the users of the CPA-EE combination. The therapeutic outcome was better in the CPA-EE group, especially in cases of facial acne (p less than 0.05). Seborrheic symptoms also responded better to the CPA-EE therapy. The results show that the CPA-EE combination is superior to the DG-EE combination in the treatment of acne and seborrhoea.

Acne Vulgaris↗
PubMed1988

Studies on the effects of the antiandrogen cyproterone acetate on social encounters between pairs of male mice.

An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely responses to variations in the degree of attack to which animals were subjected. The antihormone also had actions on other aspects of behavior including sexual activity, social investigation and immobility in such tests. CA had a potent suppressive action on the weights of sex accessory glands. The data do not suggest that CA can be used as a specific antihostility agent.

Androgen Antagonists↗
PubMed1991

[Androcur (cyproterone acetate in sex offenses--follow-up of psychiatric admissions].

This paper presents the follow-up study of 31 sexual offenders with diminished criminal responsibility or irresponsibility who were treated with Androcur (cyproterone acetate, CPA) in depot injection form connected with psychotherapy during and after their legal psychiatric hospitalisation. There were paedophiliac, exhibitionistic, hetero-sexual aggressive, and mixed sexual deviant acts. 30 patients were visited by the author in their environment, 1 patient had died. Half of the patients had a hetero-sexual relationship. 3 patients had children. 28 of the 31 patients were free. After the treatment with CPA 2 kinds of relapses could be distinguished: homologue r. (4 pat.) and residual r. (5 pat.). As to the duration of the treatment after discharge, 2 groups of patients can be distinguished: 1 group needed Androcur for a comparatively short time (up to c. 3 years), the other group for a longer time (up to c. 5 years). The anti-androgenic treatment was accompanied by psychotherapy and social therapy as well as during the hospitalisation and after discharge. The mutual effect of Androcur and psychotherapy was successful as is to be seen by the final result of this follow-up study.

Adult↗
PubMed1991

Treatment of hirsutism by an association of oral cyproterone acetate and transdermal 17 beta-estradiol.

Twenty-four hirsute women were treated with an inversal sequential scheme of cyproterone acetate, 50 mg/d by oral route from the 1st to the 15th day of the menstrual cycle, along with 100 micrograms/24 h of 17 beta-estradiol transdermally administered from days 1 to 21, for nine cycles at weekly intervals. The acne and seborrhea as well as hirsutism showed a significant improvement in all subjects studied. The plasma testosterone and dehydroepiandrosterone sulfate decrease from 1.5 +/- 1.3 ng/mL and 6.9 +/- 1.3 micrograms/mL to 0.5 +/- 0.03 ng/mL and 2.7 +/- 1.7 micrograms/mL, respectively. Similar values were observed in subjects with idiopathic hirsutism during the treatment. The metabolic parameters, as well as the plasma levels of sex hormone-binding globulin, appeared unaffected by the therapy. Furthermore, the luteinizing hormone and follicle-stimulating hormone secretion was strongly inhibited from the first cycle of treatment. In conclusion, considering the good clinical results and the avoidance of any hepatic effect, this association should be taken into account in the treatment of hirsutism, especially in case of oral estrogen intolerance.

Administration, Cutaneous↗
PubMed1991

[Multicentric clinical trial of a combination of 35 micrograms of ethinylestradiol and 2 mg of cyproterone acetate].

The authors report the results of an open multicentric study of 136 women treated by a combination of 35 micrograms ethinylestradiol and 2 mg cyproterone acetate for cutaneous manifestation of hyperandrogenism. No pregnancy occurred during the treatment of 12 months. Comparison between the last treated and non treated cycle showed a significant difference (p less than 0.001) in the severity of acne lesions regardless of their sites. General and gynaecological tolerance were excellent.

Acne Vulgaris↗
PubMed1991

[Combination of cyproterone acetate and natural estrogens in the treatment of hirsutism].

The effects of oral administration of cyproterone acetate (CPA) (50 mg) associated with natural estrogens, was investigated in two groups of hirsute women. One group received 17-beta estradiol valerianate (E2) (2 mg) (n = 22) and the other, micronized E2 (2 mg) plus estriol (E3) (1 mg) daily (n = 22) for 21 days every month. After a six month period of treatment, hirsutism improved in 70% of the patients. The more frequent adverse effect was amenorrhea. Except in one, weight gain was prevented by a low calorie diet in overweight patients. During treatment, the plasma concentration of E2 was within the normal range for the follicular phase, whereas estrone was higher, and significantly (p less than 0.001) higher under E2 + E3 than under E2 alone (43.5 +/- 29.1 vs 23.9 +/- 6.1 ng/dl). The binding capacity of sex-steroid binding-protein (SBP) was increased by E2 + E3, and was not affected by E2; transcortin levels were unchanged during treatment. The plasma levels of SBP-unbound testosterone and of delta 4-androstenedione were significantly suppressed by CPA, while DHEAS was not significantly reduced. We concluded that oral administration of CPA and natural estrogens, is a well tolerated and efficient treatment of hirsutism.

Adolescent↗
PubMed1990

Induction of dorsolateral prostate adenocarcinomas and other accessory sex gland lesions in male Wistar rats by a single administration of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl after sequential treatment with cyproterone acetate and testosterone propionate.

Groups of 20-25 male Wistar rats (Cpb:WU), nine groups of 4-week-old rats, and nine groups of 8-week-old rats, were given cyproterone acetate (CA) s.c. or by gavage daily for 18 days at a dose of 50 mg/kg/day. Directly following CA treatment, the rats received 3 daily s.c. injections with testosterone propionate (TP) at a dose of 100 mg/kg/day. On the day after the last TP administration, a single dose of one of the following carcinogens was given to 3 groups: N-methyl-N-nitrosourea (MNU), 50 mg/kg i.v.; 7,12-dimethylbenz(a)anthracene, 30 mg/kg i.v.; 3,2'-dimethyl-4-aminobiphenyl, 250 mg/kg s.c. Three other groups received the same carcinogen treatments after 7 days of recovery from the CA administration. The last 3 groups received carcinogen without TP treatment, but immediately after CA pretreatment was stopped. A 25% incidence of invasively growing, metastasizing adenocarcinomas was found in the dorsolateral prostate region of 8-week-old rats that had received MNU after treatment with CA plus TP. In addition, this group had a 5% incidence of carcinoma in situ and a 5% incidence of atypical hyperplasia in the dorsolateral prostate. Lower incidences of adenocarcinoma of the dorsolateral prostate region and of carcinoma in situ and atypical hyperplasia of the dorsolateral prostate were found in other groups that were treated with MNU or 7,12-dimethylbenz(a)anthracene after pretreatment with CA, followed by TP or recovery, but never in rats that had been treated with CA only. In the groups treated with 3,2'-dimethyl-4-aminobiphenyl, which is slowly metabolized, these lesions were also found in groups that were pretreated with only CA. The carcinomas seemed to originate from the dorsolateral prostate and their average latency time was approximately 61 weeks. The 8-week-old rat given a MNU injection after sequential treatment with CA and TP may provide a relevant animal model for human prostatic cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Effect of cyproterone acetate on testis of albino rats: ultrastructural and biochemical approach.

The animals were treated with cyproterone acetate (1 mg/100 g body weight) for 60 days after which the testicular tissue was studied at the ultrastructural level to determine the stage at which the effect took place and to study the magnitude of the effect. The testis showed changes in Sertoli cells, Leydig cells, germ cells and in the spermatids. To correlate these changes, important marker enzymes and other biochemical parameters essential for spermatogenesis were studied after 30 days and 60 days of the treatment. They registered a decrease in their levels as compared with the controls.

Androgen Antagonists↗
PubMed1990

[Hepatitis after treatment with cyproterone acetate. Apropos of a case].

Regarding a case of little-differentiated adenocarcinoma of prostate in a 79-year old male patient undergoing antiandrogenic corticosteroid therapy (cyproterone acetate), the authors describe a rare complication related to treatment with the drug. Cytolytic icterus, without cholestasis, occurred eleven weeks after starting the treatment without metastasis of the primary cancerous lesion, and regressed when administration of the antiandrogenic agent was interrupted. This description is compatible with toxic hepatitis. This is a rare complication, which should be differentiated from stasis icterus consecutive to treatment with progestogens. Its diagnosis precludes also primary or drug-induced secondary tumors or degenerative hepatic lesions. A knowledge of this complication by the urologist is important, so the latter might not conclude too hastily to metastatic extension of primary cancer of prostate. Withdrawal of the patient from antiandrogenic therapy is mandatory, and management should incorporate complete biological investigation of liver function, CT scans and, depending upon the case, liver biopsy as the only means of studying this exceptionally rare complication.

Adenocarcinoma↗
PubMed1985

[Ambulatory treatment of sex offenders with cyproterone acetate (Androcur). A catamnestic study].

The authors report about the catamnestic inquiry concerning 13 patients with sexual problems treated with cyproterone acetate (CA) of whom 12 relapsed repeatedly in sexual delinquency. Since 1972 the Basle University Psychiatry Outpatient-Department treated 12 of these patients with CA-tablets and psychotherapy. One patient was treated in the same way by a head physician of the Basle University Psychiatry Hospital. Reason for CA-intake: 6 patients took CA because they were obliged by legal order. 4 patients were "voluntarily" ready to take CA for fear of imprisonment. 2 patients who were not accountable for their crimes were treated with CA and one patient desired CA-medication because he suffered from his masochism severely. The mean age of the patients was 34.5 years, the mean daily dosage 115 mg. Result of CA-therapy and psychotherapy: 11 patients (85%) did not relapse under CA treatment which lasted on the average three years. 3 patients succeeded under CA treatment with full social integration. 3 patients showed an improvement of social integration and 3 patients one of whom received Disulfirame (Antabus) reduced alcohol intake. After having ended or interrupted CA-medication two of 7 patients relapsed. 3 patients who did not relapse after stopping the CA-intake were observed for as long as 3 years. As forensic psychiatric consequence it follows that CA in combination with psychotherapy can be considered--in spite of the side-effects linked with it--as a method of choice in the ambulatory treatment of sexual delinquents who have frequently relapsed and whom psychotherapy alone did not help.

Adult↗
PubMed1989

Testicular changes after treatment with a GnRH analog (buserelin) in association with cyproterone acetate in men with prostatic cancer.

Twelve patients (age range: 53-78 years) with prostatic cancer were treated with Buserelin (1.2 mg/day) and cyproterone acetate (150 mg/day). Testicular biopsies performed after 13-96 weeks of treatment were compared to those obtained from 6 untreated men of similar age. Deranged spermatogenesis was observed in all but 1 treated patient. The appearance of immature Sertoli cells and atrophic Leydig cells suggests a condition of pharmacologic 'hypophysectomy'. The variable damage to the seminiferous epithelium and findings of an incomplete involution of Leydig cells suggested a decreased but still present testicular steroidogenesis.

Aged↗
PubMed1989

[Effects of cyproterone acetate on mouse submandibular gland].

It is recognized that the submandibular gland (SMG) of mice is one of the target organs for androgen, and a specific androgen-binding protein (androgen receptor) has been found in the cytosol fraction of this gland. Androgen participates in the production of histochemically and biochemically detected components of this gland through this receptor. Cyproterone acetate (CPA) is a synthetic progestogen which possesses antiandrogenic properties with some synandrogenic action. However, the action of CPA on the SMG has not been well defined. In the present study, the effects of CPA on the granular duct (GD) of the mouse SMG, which is the site of androgen action, were investigated using histometric, histochemical, and biochemical techniques. For histometric and histochemical experiments, normal adult male mice were treated with CPA (20, 40 and 80 mg/kg, S.C.) every second day for 5-30 days. In other experiments, castrated (CAS) and castrated-adrenalectomized (CA) mice were prepared, and they were given an injection of testosterone propionate (TP; 20 mg/kg, S.C.) and/or CPA (20 and 200 mg/kg, S.C.) every second day for 10 days. After the final administration, SMG weights were determined and the size of the GD in the SMG was measured by light microscopy using a micrometer. The sections of SMG were stained with methylgreen-pyronin, bromophenol blue, and p-dimethylaminobenzaldehyde in order to detect RNA (RNA staining), total protein (BPB staining), and granules (Try staining) in the GD, respectively. The intensity of each staining was measured by the method of Sato et al. For biochemical experiments, the mice with testicular feminization (Tfm), which are genetically deficient in androgen receptor, and genetically normal male (X/Y)-castrated mice were used. Both Tfm and X/Y-castrated mice were injected with CPA for histological experiments. After the administration period, the SMG's of both Tfm and X/Y-castrated mice were isolated and esteroprotease activity was determined by the method of Trautschold. The SMG of non-administered X/Y-castrated mice was homogenized in Tris-HCl buffer. And cytoplasmic extracts of SMG's from non-administered X/Y-castrated mice were prepared for detection of inhibitory effect of CPA on specific binding pattern of 3H-methyltrienolone (R1881) by the sucrose density gradient method.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Use of cyproterone acetate to lower circulating corticosterone and its effects on lymphocytes in domestic fowl.

Chickens were given daily injections of cyproterone acetate (CA) and the effects on plasma corticosterone, bodyweight, weights of the adrenals and lymphoid organs, numbers of circulating peripheral blood lymphocytes and their proliferation in the presence of lectins, concanavalin A (Con A) and phytohaemagglutinin (PHA), were investigated. Five daily doses of 10 or 30 mg CA kg-1 bodyweight each week over a three-week period caused a decrease in weight gain and a reduction in the relative weights of the bursa and thymus but not the spleen. There was a small decrease in the adrenals after treatment with 10 mg CA kg-1. When daily injections of CA were given over a seven-day period doses of 6 and 10 mg CA kg-1 bodyweight caused a significant (P less than 0.05) decrease in plasma corticosterone concentration after four days. However, after eight daily injections of CA a single injection of corticotrophin (10 iu ACTH kg-1) increased circulating corticosterone indicating CA had not completely blocked adrenal synthesis. CA had no effect on numbers of circulating peripheral blood lymphocytes or their ability to proliferate in the presence of Con A or PHA. The results indicate that CA is effective in lowering circulating corticosterone in the fowl but this did not affect the numbers or responsiveness of peripheral blood lymphocytes.

Adrenocorticotropic Hormone↗
PubMed1987

Reversible sterility by cyproterone acetate plus testosterone enanthate in langur monkey with maintenance of libido.

Cyproterone acetate (1 mg/kg b.w. per day; oral) in combination with testosterone enanthate (2 mg/kg b.w. 15 days; i.m.) was administered for 60 and 90 days into adult male langur monkeys (Presbytis entellus entellus, Dufresne). Testicular weight and volume were reduced significantly. Spermatogenesis was suppressed but the interstitial cells appeared normal. Seminiferous tubules and Sertoli cell nuclear diameters were reduced significantly. The indices of testicular steroidogenesis, i.e. testicular total proteins, sialic acid, RNA and fructose showed a fall. On the contrary, cholesterol, total lipids, glycogen and phosphatases increased after treatment. Libido was not affected. Cessation of treatment resulted in a resumption of all the variables to normal levels within 90 days. The results reveal a reversible inhibition of testicular steroidogenesis which ultimately resulted in the disruption of spermatogenesis, a definite index of sterility. It is further emphasized that simultaneously administered testosterone enanthate maintains androgenicity.

Animals↗
PubMedDate not supplied

A new association of ethinylestradiol (0.035 mg) cyproterone acetate (2 mg) in the therapy of polycystic ovary syndrome.

The authors treated 28 patients with polycystic ovary syndrome (PCOS) with the new preparation SH B 209 AE consisting of 0.035 mg of ethinylestradiol and 2 mg of cyproterone acetate (EE + CPA) throughout 12 months. From the analysis of the endocrine and clinical modifications induced by the drug along with the negligible incidence of side effects the conclusion can be drawn that this new estro-progestational association is indicated in the therapy of PCOS.

Acne Vulgaris↗
PubMed1986

[Hormonal modulation in disseminated lupus erythematosus: the preliminary results with danazol and cyproterone acetate].

In an open prospective study, we have tested clinical efficacy and tolerance of two antigonadotropic drugs, that is danazol (D) and cyproterone-acetate (CA). This study was performed in 11 female patients ranging in age from 19 to 47 years, who suffered from midly-active SLE, during 12 therapeutic periods on the whole (that is 6 for each drug), the minimum period of which was one year. Because of side-effects, D had to be early withdrawn in 2 patients, whereas (the) AC appeared to be well-tolerated in all of them. On the whole, 16 clinical exacerbations of DLE were observed during the 12 months pre-treatment period, versus 9 exacerbations during the 12 months treatment period (p less than 0.05, Wilcoxon test), whereas the average dose of prednisone was reduced from 9.6 to 3.5 mg/day. A dramatic improvement was then observed in 3 patients suffering from mucous ulcerations. Increased plasma testosterone level without any change in estradiol level was observed in patients treated with D. Conversely, plasma estradiol decreased without any change in testosterone level in patients treated with CA. Both drugs induced reduction in plasma sex-hormone binding protein. These preliminary results suggest that D and CA may both reduce lupus disease activity, in parallel with an hormonal environment modification, towards a lower estrogen-androgen balance, along with a better tolerance as for CA.

Adult↗
PubMed1986

Clinical efficacy and safety of cyproterone acetate in severe hirsutism: results of a multicentered Canadian study.

We compared the efficacy and safety of cyproterone acetate (Shering AC, Berlin, FRG) at a low (Diane, 2 mg) or a high dose (Androcur, 100 mg) in the treatment of 158 patients with severe hirsutism. At baseline, no difference was observed in mean hirsutism total index (19.5 Diane versus 20.1 Androcur) or distribution (facial, bust, or abdomen). By the end of the study, patient loss in Diane and Androcur groups was 29.1% and 27.8%, respectively, and the mean percent difference in the scoring index was as follows: total, 24.6 Diane versus 30.8 Androcur, P less than 0.05; facial, 30.1 Diane versus 33.0 Androcur, P less than 0.10; bust, 12.1 Diane versus 31.2 Androcur, P less than 0.02; and abdomen, 20.1 Diane versus 31.2 Androcur, P less than 0.02. Except for breast tenderness (Diane greater than Androcur), amenorrhea, and weight gain, (Androcur greater than Diane), the incidence of side effects was comparable in both groups.

Adolescent↗
PubMed1987

Effects of a cyproterone-containing oral contraceptive on hormonal levels in polycystic ovarian disease.

The management of polycystic ovarian disease in women not desiring pregnancy is controversial. To avoid the progressive androgenic effects on peripheral target organs, some advocate the use of oral contraceptives. This study reports the effects of a preparation with 50 micrograms ethinyl estradiol and 2 mg cyproterone acetate on gonadotropins, prolactin, testosterone, sex hormone binding globulin (SHBG), androstenedione, and calculated free testosterone index before and after six months of treatment. Gonadotropins, testosterone, and androstenedione levels decreased, prolactin did not change, and sex hormone binding globulin increased as the result of the treatment. This led to a net decrease in the calculated free testosterone.

Contraceptives, Oral, Hormonal↗