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PubMed1981

Effect of cyproterone acetate on pituitary-adrenocortical function in man.

Recent literature (1973-1976) suggests suppression of pituitary-adrenal function in patients (eg with pubertas praecox) who are treated with cyproterone acetate in high doses for prolonged periods. Therefore we investigated in our metabolic ward the effects of administration of 200 mg cyproterone acetate per day during 20 days to 4 healthy male volunteers. Baseline plasma cortisol and ACTH levels, repeated diurnal plasma cortisol and ACTH profiles and the results of tetracosactide (Synacthen) stimulation tests and single-dose metyrapone (Metopiron) tests proved to be comparable before, during and after treatment. Moreover, a slight gradual increase in urinary cortisol excretion during the observation period indicated that cyproterone acetate in the given dose during 20 days certainly does not reduce the pituitary-adrenal function of 4 healthy male volunteers. Long-term administration (during 1 to 7 years) of the combination of cyproterone acetate and ethinyloestradiol did not suppress serum levels of cortisol, prolactin, thyroxine and TSH in 18 female patients with hirsutism and/or acne.

Adrenocorticotropic Hormone↗
PubMed1980

[Serum prolactin levels during therapy of prostatic cancer with oestradiol-17 beta-undecylate and cyproterone acetate (author's transl)].

Sixteen patients aged from 50 to 79 years with inoperable prostatic cancer were allocated at random to treatment either with 300 mg cyproterone acetate at weekly intervals or with 100 mg oestradiol-17 beta-undecylate every month. Blood samples were taken before treatment and at monthly intervals during the 6-month period of treatment. Serum prolactin levels were determined by a double-antibody radioimmunoassay. Basal serum levels of prolactin were 7.76 +/- 4.84 ng/ml and 9.50 +/- 4.32 ng/ml in the two groups of patients before therapy with oestradiol-17 beta-undecylate or cyproterone acetate, respectively. These pretreatment serum prolactin levels were statistically indistinguishable. Serum prolactin levels did not rise significantly during the first 5 months of treatment with cyproterone acetate, although an increase in prolactin was found in the sixth months of therapy with the antiandrogen. On the other hand, oestradiol-17 beta-undecylate raised serum prolactin levels significantly already after one month of treatment and the mean values were significantly higher than in the antiandrogen-treated group. These data combine to suggest cyproterone acetate as a suitable alternative to oestrogens in the therapy of inoperable prostatic cancer.

Aged↗
PubMed1981

Effect of cyproterone acetate and its metabolites on the adrenal function in man, rhesus monkey and rat.

The effect of oral administration of 17 alpha-acetoxy-6-chloro-1,2 alpha-methylene-4,6]pregnadiene-3,20-dione (cyproterone acetate, Androcur) on the adrenal function in male hypersexual subjects and in female rhesus monkey was investigated on the basis of cortisol and ACTH levels in serum or plasma and excretion of cortisol and 17-ketosteroids. In addition, cyproterone acetate and its main metabolite alcohol of the main metabolite were characterized for treatment of male hypersexual subjects and female rhesus monkeys did not reveal any signs of adrenal suppression. Cyproterone acetate and its metabolites gave on indication of any appreciable anti-inflammatory effect in the adjuvant edema test in rats. However, there was a general increase in the level of blood glucose and liver glycogen as well as a reduction in body weight and organ weight (spleen, thymus and adrenal) in rats, in which 15 beta-hydroxy cyproterone was slightly more active with the exception of adrenal weight tests. It can be concluded that adult man and rhesus monkey are much less sensitive, is so at all, to some corticosteroid-like activities of cyproterone acetate and its main metabolites than the rat.

17-Ketosteroids↗
PubMed1999

Cirrhosis in a child with hypothalamic syndrome and central precocious puberty treated with cyproterone acetate.

UNLABELLED: Before the advent of gonadotropin-releasing-hormone analogues, cyproterone acetate (CPA) had been widely prescribed for the treatment of precocious puberty. Although it is usually well tolerated, liver toxicity has been recognized as a complication of its long-term use. We report the occurrence of cirrhosis in a 10-year-old boy with hypothalamic syndrome and precocious puberty who was treated with CPA for over 50 months. Despite discontinuation of the medication, the liver disease progressed. The patient died of sepsis and multiorgan failure at the age of 14 years. This is the first paediatric report of substantial liver damage and liver toxicity progressing to cirrhosis associated with CPA treatment. CONCLUSION: Prolonged cyproterone acetate treatment may induce cirrhosis. Monitoring of liver function both during treatment and for several months after discontinuation of therapy is recommended.

Adolescent↗
PubMed1999

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers.

OBJECTIVE: To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN: Experimental in vitro prospective study. SETTING: An academic research laboratory. INTERVENTION(S): Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S): Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S): Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S): Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

Cell Adhesion↗
PubMed1977

Effect of cyproterone acetate on prolactin secretion in the female Rhesus monkey.

Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40 mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.

Animals↗
PubMed2000

beta-glucuronidase activity is elevated in the rat harderian gland after bromocriptine but decreased after cyproterone acetate treatment or castration. Postcastrational effects on the ultrastructure of the gland.

OBJECTIVE: To investigate the effect of castration, bromocriptine and cyproterone acetate treatment on lysosomal hydrolytic enzymes and ultrastructure of the rat Harderian gland. METHODS: Groups of rats were subjected to the treatment by bromocriptine, cyproterone acetate and castration. Harderian glands were dissected from each experimental animal cut into small pieces and immediately stored in liquid nitrogen. Only those from castrated animals were fixed in Karnovsky fluid and processed for electron microscopy. The activity of acid phosphatase and ss-glucuronidase were estimated by kits from Sigma (St. Louis, Mo, USA). Semi-thin sections were stained with 1-% toluidine blue and ultra-thin sections with uranyl acetate and counter-stained with lead citrate. The examination was performed by Joel JEM-1200 EX II electron microscope. RESULTS: The treatment of male rats with the prolactin release inhibitor bromocriptine induced a significant increase in ss-glucuronidase activity. On the contrary, such activity was significantly decreased after treatment with the testosterone receptor antagonist cyproterone acetate as well as after castration. However, these treatments did not alter the activity of lysosomal acid phosphatase. Castration induced dramatic changes mostly in type A cells such as the appearance of lipid vacuoles with irregular forms and the predomination of smooth endoplasmic reticulum (SER) throughout the cytoplasm. The most dramatic postcastrational change was the degeneration of the mitochondria. These changes in type A cells might be due to the uneven distribution of the testosterone receptors in the rat Harderian gland, which are more numerous in type A cells. CONCLUSIONS: the gland physiology is responsive to alteration in circulating prolactin and testosterone levels.

Acid Phosphatase↗
PubMed1996

Testotoxicosis proved by immunohistochemical analysis and successfully treated with cyproterone acetate.

We present a case of testotoxicosis diagnosed on the basis of immunohistochemical investigation of the testis. The patient was treated with the antiandrogen cyproterone acetate at a dose of 70-130 mg/m2/day. Clinical and biochemical features are consistent with the diagnosis of testotoxicosis. The long-term experience with cyproterone acetate had been generally satisfactory. There are, to our knowledge, no reports on cyproterone acetate treatment of testotoxicosis.

Age Factors↗
PubMed1994

[Acceptability, tolerance and quality of life impact of cyproterone acetate treatment in female hirsutism. Comparison of 2 protocols in combination with oral or transdermal estradiol].

67 women (aged 16-40) with hirsutism and/or other signs of hyperandrogenism (acne, androgenic alopecia, cycle disturbances) have been treated for one year with cyproterone acetate + estradiol. Patients have been randomly assigned to therapy with cyproterone acetate and estradiol valerate per or cyproterone acetate and transdermal estradiol. Acceptance, tolerance and effects on quality of life of this treatment have been assessed using a self questionnaire completed with questions for assessment for compliance. Among patients who have had a full course of treatment, 54 have fulfilled the end-of-study quality of life questionnaire. The queries allow calculation of a relational well-being score and of an emotional well-being score. The answers to the initial questionnaire show in a high percentage of patients emotional trouble (depressive state, anxiety, irritability) and disturbances in relational life. The hirsutism score has been found to be significantly correlated with anxious trouble but not with the global quality of life score. The treatment has resulted in a significant improvement in acceptance of being exposed to view (p < 0.01), self-assurance (p < 0.01) as well as emotional well-being score (p < 0.05), without any significant difference between the 2 therapeutics groups. Measurement of treatment acceptance with a visual analogic scale has been found globally very satisfactory by patients from the 2 groups. Compliance of treatment with transdermal estradiol turned out to be lesser in younger patients but is better in patients in whom emotional balance has been improved by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1986

Control of hidradenitis suppurativa in women using combined antiandrogen (cyproterone acetate) and oestrogen therapy.

The effects of combined treatment with the antiandrogen, cyproterone acetate, and ethinyl oestradiol on four women with long-standing hidradenitis suppurativa have been investigated. The condition was controlled successfully in all patients with 100 mg/day cyproterone acetate using the reversed sequential regimen; lowering the antiandrogen to 50 mg/day caused deterioration. Before treatment, plasma testosterone levels were within the normal range, but plasma androstenedione values were raised and sex hormone binding globulin levels were low. On treatment, the androstenedione concentration fell and sex hormone-binding globulin values were raised. However, since these levels were unaltered by reducing the antiandrogen dosage, the main action of the therapy is probably that of the antiandrogen within the target cells.

Adult↗
PubMed1980

The effect of cyproterone acetate on serum testosterone, LH, FSH, and prolactin in male sexual offenders.

The anti-androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21-31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6-28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

Adult↗
PubMed1986

Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group.

Patients with previously untreated category T3 to T4 Mo or Ml prostatic cancer were allocated randomly to receive 250 mg. cyproterone acetate per day, a loading dose of 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks followed by 100 mg. orally twice daily, or 1 mg. diethylstilbestrol 3 times daily in a phase III trial (protocol 30761) performed by the genitourinary tract cooperative group of the European Organization for Research on the Treatment of Cancer. Of 236 patients entered 210 were eligible: 75 received cyproterone acetate, 71 medroxyprogesterone acetate and 64 diethylstilbestrol. Local and distant tumor response, time to progression, survival and toxicity were assessed. Patients treated with medroxyprogesterone acetate had a less favorable course with a shorter duration of survival and time to progression than those treated with the other 2 drugs. There was no significant difference between diethylstilbestrol and cyproterone acetate. Cardiovascular side effects were reported more often in patients treated with diethylstilbestrol than in those treated with cyproterone acetate but severe and lethal cardiovascular toxicity was relatively low in all groups. Other side effects were negligible. Further studies are required to establish the influence of effective hormonal treatment upon survival.

Aged↗
PubMed1997

An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men.

OBJECTIVE: To test the effectiveness, safety, and reversibility of the combined administration of cyproterone acetate and T undecanoate. DESIGN: Open clinical trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Eight healthy men, aged 25-42 years were selected. INTERVENTION(S): Cyproterone acetate, 12.5 mg, and T undecanoate, 80 mg, were administered orally twice daily for 16 weeks. MAIN OUTCOME MEASURE(S): Semen analyses every 2 weeks; physical examination, chemistries, hematology, prostatic-specific antigen, gonadotropins and T levels, and a questionnaire on sexual and behavioral function every 4 weeks. RESULT(S): In all subjects a profound suppression of spermatogenesis occurred; one subject became azoospermic, five subjects had sperm counts of < or = 3 x 10(6)/mL, and in two subjects sperm counts were 4 and 6 x 10(6)/mL in week 16. Sperm counts returned to baseline in all men after hormone administration was discontinued. No changes in metabolic parameters and total prostatic-specific antigen were detected. Hemoglobin and hematocrit decreased statistically significantly at week 16 of treatment and returned to baseline by week 12 of recovery. There was no change in sexual function or behavior. CONCLUSION(S): The oral administration of T undecanoate plus cyproterone acetate induces a profound suppression of spermatogenesis with no major adverse effects. These data suggest the feasibility of oral contraception in men.

Adult↗
PubMed1999

Long-term sequential treatment with combined estradiol valerate and cyproterone acetate in early postmenopause.

BACKGROUND: We sought to evaluate the long-term safety and efficacy of cyclic combined estradiol valerate and cyproterone acetate. METHODS: A six-year, single center, open study was performed of forty-eight recently postmenopausal women. We evaluated biochemical markers of bone turnover, bone mineral content, bone mineral density, serum lipids, climacteric symptoms, and bleeding throughout the six-year period. Ultrasound evaluation of the endometrium was performed yearly for the first two years. RESULTS: Markers of bone turnover were decreased over the study period, while bone mineral content and density remained unchanged. High density lipoprotein cholesterol levels were increased with unchanged blood pressure over the six years. Menopausal symptoms showed significant improvements within 6 months. Endometrial scan results never required hysteroscopic evaluation. CONCLUSION: Sequentially combined estradiol valerate and cyproterone acetate can be used for an indefinite number of years in women with recent natural menopause. Cyproterone acetate provides adequate endometrial protection and cycle control while allowing estradiol valerate to exert its positive effects on lipid profile, bone metabolism, and climacteric symptoms.

Cyproterone Acetate↗
PubMed1981

Effects of oestrogens, orchidectomy and cyproterone acetate on salt and water metabolism in carcinoma of the prostate.

Salt and water metabolism was investigated during treatment with oestrogens and with cyproterone acetate and after orchidectomy in 46 patients. An increase in plasma volume was noted during oestrogen treatment and a slight transitory rise in plasma volume was also seen after orchidectomy. During cyproterone acetate therapy there was a reduction of body weight and a transitory increase in 24-hour urine volume and urinary sodium excretion. The increase in plasma volume during oestrogen treatment might tax the circulatory capacity. Cyproterone acetate treatment does not change the salt-water balance or the plasma volume in such a way that the risk of congestive heart failure could be increased.

Aged↗
PubMed1979

[Experience with the anti-androgen cyproterone acetate in the management of hirsutism].

Use of the antiandrogen cyproterone acetate in the treatment of hirsutism.--25 women with hirsutism or hypertrichosis faciei were subject to a "reverse sequential therapy" with cyproterone acetate (Hammerstein's regimen) for 1 to 3 years. In 8 patients, a limited, in 14 patients a satisfactory and in one woman a good result could be recorded. Cycle irregularities and subjective side effects were within a tolerable range. Studies of the hair pattern in 15 patients revealed a higher telogen rate as well as increased diameters of the hair stalks, compared with controls, in the temporal region of the head. These alterations disappeared in the course of the treatment. In the parietal region of the head no significant differences of the hair pattern were found in comparison with the controls and during application of the steroids.

Cyproterone↗
PubMed2005

Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer--a pilot study.

OBJECTIVE: To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer. PATIENTS AND METHODS: In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to goserelin acetate and continued for 21 days thereafter. PSA, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were obtained before treatment and on days 6, 8, 10, 16, 21 and 28. Primary end point was PSA. Hormone profile and clinical features including urinary symptoms and bone pain were secondary end points. RESULTS: Both groups were equally matched apart from serum creatinine and ALP. The speed and magnitude of the percentage change in median PSA from baseline was increased for the CPA group but there was no statistically significant difference in the two groups. Although those receiving bicalutamide all showed a testosterone peak, this remained within the normal range. No difference in the frequency of drug-specific adverse events was found. None of the patients died or developed cord compression during the study period. CONCLUSION: Bicalutamide is able to suppress the initial PSA surge as effectively as cyproterone acetate albeit slightly delayed. A statement whether bicalutamide is equally good at preventing clinical flare cannot be made and should be assessed in an appropriately powered study.

Aged↗