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At least 199 records · Page 11Linked to original sources
PubMed1986

Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762.

Two randomized trials were started in 1976 by the European Organization for Research on Treatment of Cancer urological group. Trial 30761 compared 1 mg. diethylstilbestrol orally 3 times daily to 250 mg. oral cyproterone acetate daily and to 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks, then 200 mg. orally daily. Trial 30762 compared 3 mg. diethylstilbestrol to 560 mg. estramustine phosphate orally for 8 weeks and then 280 mg. daily. The 239 patients in study 30761 and 226 in study 30762 were evaluated for cardiovascular toxicity during treatment. Various types of side effects (fluid retention, hypertension, electrocardiographic changes, myocardial infarction and thromboembolic disease) and their degrees of severity were analyzed. In both studies the most frequent type of cardiovascular toxicity was represented by fluid retention. Cardiovascular toxicity as a whole was higher with diethylstilbestrol than with estramustine phosphate or medroxyprogesterone acetate therapy, and was the lowest with cyproterone acetate therapy. The risk of severe cardiovascular complications developing was the highest during the first 6 months of treatment. Increasing age, body weight greater than 75 kg. and, especially, the presence of previous cardiovascular disease represented adverse factors in the development of cardiovascular toxicity.

Aged↗
PubMed1992

Apoptosis, cell proliferation and c-ras expression during and after cyproterone acetate (CPA) induced liver hyperplasia.

Cell proliferation and cell death appear in several systems as mutually exclusive, which raises the assumption that a same factor or secondary signal(s) might exert opposite control on the two processes. To test this assumption we investigated the time-course evolution of the S phase and apoptotic indices in rat liver during cyproterone acetate (CPA) induced hyperplasia and during the recovery of normal liver mass provoked, respectively, by cyproterone acetate (CPA) treatment and withdrawal. The levels of c-myc and c-ras transcripts were also followed in view of the indications of a positive role of these oncogenes in proliferation. The data showed that proliferation and cell death are not always mutually exclusive and that a high rate of cell death was indifferently associated with high or low c-ras expression. Our data are consistent with a role of this gene in proliferation but exclude that it plays an opposite role in controlling cell death.

Animals↗
PubMed1990

Determination of megestrol acetate and cyproterone acetate in serum of patients with advanced breast cancer by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method with ultraviolet detection of megestrol acetate and cyproterone acetate in human sera is described. The proposed assay is linear up to 1400 ng/ml (r = 0.999) and has a detection limit of 5 ng/ml. Recoveries of both compounds in spiked sera were ca. 95%; inter-assay coefficients of variation were 4.0 and 3.1% and intra-assay values were 1.3 and 1.4%, respectively. For validation of the method we also developed a gas chromatographic-mass spectrometric method for both steroids. The results obtained by the two methods showed good correlation: for megestrol acetate r = 0.98, n = 31, p less than 0.0001, and for cyproterone acetate r = 0.94, n = 0, p less than 0.0001. Large inter-individual differences in the serum concentrations of both substances were found in groups of patients with metastatic breast cancer receiving the same oral load of either steroid.

Antineoplastic Agents↗
PubMed1988

Metabolic effects of combined cyproterone acetate and percutaneous 17 beta oestradiol after six and twelve months therapy in 61 patients.

The metabolic effects of combined cyproterone acetate (50 mg) and percutaneous 17 beta oestradiol were studied during one year in 61 patients admitted for hyperandrogenia. Before treatment and at 6 and 12 months the following tests were performed: oral glucose tolerance test (OGTT) with insulinemia dosage, determination of total cholesterol, LDL, VLDL and HDL fractions, triglycerids, A1 and B apoproteins, liver function tests: bilirubinemia, alkaline phosphatases, transaminases and gamma glutamyl transferases. The patients' mean age was 27.0 +/- 6.8 years, the body mass index was 22.4 +/- 3.5 kg/m2. After one year of treatment the body mass index was not modified. Blood glucose slightly increased during OGTT; at 6 months this was significant at +30 minutes, at 12 months at +30, +60 and +90 minutes (P less than 0.05). There was no variation in insulinemia during OGTT. Total cholesterol decreased significantly at 6 and 12 months (P less than 0.001), this was associated with a decrease in HDL cholesterol, but without modification of the LDL + VLDL/HDL ratio. Decrease in HDL cholesterol was associated with a significant decrease in A1 apoproteins. No change in triglycerids and in liver function tests was observed at either date. In conclusion the metabolic effects of this association are described. These effects are minimal compared to those observed with cyproterone acetate and ethinyl oestradiol association in the literature. However, attention should be drawn to the possibility of glucose intolerance and decrease in HDL cholesterol and A1 apoproteins.

Adult↗
PubMed1981

Local suppression of sebum secretion in rats by topical cyproterone acetate in ethanol.

Sebum production was measured on 2 symmetrically placed areas on the flanks of rats over alternating periods of 18 and 6 hr for 4 days, by absorbing the lipid on pads of cigarette paper held in place by a specially designed harness. Castrated rats receiving testosterone produced about twice as much sebum as untreated littermate controls. Once daily application of ethanol to one flank significantly reduced sebum production, in comparison with the other flank in testosterone-treated but not in untreated rats. Daily application of 5 mg cyproterone acetate in ethanol to one flank in a third group of rats significantly reduced sebum production in comparison with that of the other flank treated with vehicle only. The effects became significant within 24 hr. It seems likely that the sebaceous glands received the topically applied materials by way of the pilo-sebaceous orifices rather than by transepidermal absorption. The results demonstrate that one action of cyproterone acetate is at the target site and suggest that the anti-androgen may be effective when applied topically. The method could prove useful in assessing the local action on sebaceous activity of topically applied substances.

Administration, Topical↗
PubMed1984

Effect of low dose cyproterone acetate on the response of acne to isotretinoin.

Twenty-seven males with severe acne were treated for 12 weeks with 0.05 mg/kg/day isotretinoin (ten patients) or 5 mg daily cyproterone acetate (eight patients) or both drugs together in these doses (nine patients). With isotretinoin, the sebum excretion rate (SER) fell by 45% +/- 9% s.e.m. (P less than 0.0025), lesion count fell by 65% +/- 10% (P less than 0.0005) and median clinical 17% +/- 12% (NS) fall in SER, a 15% +/- 10% (NS) fall in lesion count and the median severity was unchanged. Patients unchanged. Patients treated with both drugs showed a 42% +/- 13% reduction in SER (P less than 0.005), a 68% +/- 11% decrease in lesion count (P less than 0.0005) and a decrease in median severity from 8 to 4 (P less than 0.01) which was no different from the response to isotretinoin alone. Isotretinoin increased serum cholesterol from 4.4 mmol/l +/- 0.3 s.e.m. to 4.7 mmol/l +/- 0.3 s.e.m. (P less than 0.01), serum triglyceride from 0.73 mmol/l +/- 0.07 s.e.m. to 0.96 mmol/l +/- 0.14 s.e.m. (P less than 0.05) and gamma-glutamyltransferase (GGT) from 15.9 i.u./l +/- 2.1 s.e.m. to 19.0 i.u./l +/- 2.4 s.e.m. (P less than 0.01). Comparison of the area under the concentration-time curve for triglyceride and high density lipoprotein (HDL)-cholesterol showed that the changes were smaller when isotretinoin was combined with cyproterone acetate. We conclude that the effect of isotretinoin in acne was not enhanced by the antiandrogen, but the increase in serum triglyceride and decrease in HDL-cholesterol produced by the retinoid were reduced by combination with the antiandrogen.

Acne Vulgaris↗
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↗
PubMed1987

Cyproterone acetate, an alternative gestagen in postmenopausal oestrogen/gestagen therapy.

Seventy-six healthy, early postmenopausal women (aged 45-54 years) were allocated to 2 years of treatment with a cyclic combination of 2 mg oestradiol valerate (21 d) and 1 mg cyproterone acetate (11 d) or placebo. Sixty-five women (86%) completed the study. In the placebo group the bone mineral content in the forearms (measured by single photon absorptiometry) and the bone mineral content in the lumbar spine and total skeleton (measured by dual photon absorptiometry) decreased significantly and at the same magnitude (P less than 0.001), whereas all bone mass measurements remained unchanged in the hormone-treated group. In the hormone-treated group there was a significant decrease in biochemical estimates of bone turnover (serum alkaline phosphatase, serum phosphate, fasting urinary calcium and hydroxyproline), whereas these values were unchanged in the placebo treated group. We conclude that treatment with a cyclic combination of 2 mg oestradiol valerate and 1 mg cyproterone acetate is effective as prophylaxis of postmenopausal bone loss.

Calcium↗
PubMedDate not supplied

Effects of prolonged treatment with cyproterone acetate on hydrolytic enzymes in seminal vesicles of the mouse.

Daily s.c. injections of cyproterone acetate cause a time-related decrease in the weight and beta-glucuronidase activity of seminal vesicles in mouse. Protein content shows an initial increase and subsequently, after 120-180 days of treatment, a decline (reaching control levels). Acid phosphatase activity also decreases but only after long-term treatments. 5 alpha-DHT tends to bring the values of various parameters towards the control range. However, its effects are of a lesser magnitude in animals treated for 90 days with the antiandrogen. It is proposed that the antifertility action of cyproterone acetate is due mainly to its negative influence not only on the epididymis but also on seminal vesicles.

Acid Phosphatase↗
PubMedDate not supplied

Effects of low doses of cyproterone acetate on sperm morphology and some other parameters of reproduction in normal men.

Cyproterone acetate was given to three healthy men in a dosage of 10 mg per day for 8-14 weeks. The effects on sperm count, morphology, motility and vitality was followed weekly and compared with the effects of 25 mg daily in another case. Sperm morphology included the study of live spermatozoa separately. The effects on serum levels of FSH, LH, testosterone and oestrogens was also studied. With respect to sperm count and morphology a dose-effect relationship is indicated. Abnormalities within tails and midpieces of live spermatozoa appear early and may predict sterility before azoospermia develops. FSH and oestrogens were comparatively more depressed than LH and testosterone. The results indicate that cyproterone acetate may have an androgenic (or gestagenic) effect on the hypophyseo-hypothalamic level in addition to an antiandrogenic effect on gonads and their accessory organs.

Adult↗
PubMedDate not supplied

Cyproterone acetate and a small dose of oestrogen in the pre-operative management of male transsexuals. A report of three cases.

The pre-operative treatment of three adult male transsexuals with the anti-androgen and progestogenic compound cyproterone acetate is reported. When used in combination with cyproterone acetate, only a very small dose of oestrogen is needed to induce feminisation. The effect of this treatment on both testicular and epididymal function is described.

Adult↗
PubMed1982

Long-term effects of cyproterone acetate on the pituitary adrenal axis in adult women.

Function of the pituitary-adrenal axis was assessed in 16 adult female patients who had been taking cyproterone acetate for greater than 1 year. Some evidence of reduced basal cortisol output was seen in 25% of the patients, but plasma cortisol levels could be stimulated both by hypoglycaemia and by direct corticotrophin (ACTH) stimulation. The latter effect was confirmed by analysis of steroid excretion in urine although basal excreation rates indicated extensive adrenal suppression. These results suggest that cyproterone acetate does have some glucocorticoid activity which is able partially to suppress the pituitary--adrenal axis, but leaves it still responsive to stress.

Adult↗
PubMed1986

Imprinting of male sex tissues by neonatal endogenous androgens in mice. Molecular alterations following exposure to cyproterone acetate.

This study was conducted to evaluate the growth and biochemical responsiveness of the epididymis, vas deferens and seminal vesicles of adult mice exposed to cyproterone acetate during the first 10 days of life. Results indicate that the weight and protein content of sex accessory organs were significantly depressed, testosterone and dihydrotestosterone concentrations were unaffected or increased, the number of cytosolic androgen-binding sites was slightly or significantly reduced. The efficiency of exogenous testosterone in promoting growth and protein synthesis in target organs of castrated adult males was significantly lowered by neonatal cyproterone acetate treatment. It is concluded that a deficient androgenic stimulation during neonatal life induces a limited response of sex target organs to endogenous or exogenous androgens in adulthood.

Androgen Antagonists↗
PubMed1987

Effects of cyproterone acetate on mating behavior, testicular morphology, testosterone level, and body temperature in male ferrets in comparison with normal and castrated males.

Effects of surgical castration of 60-day-old male ferrets are compared with the effects of a chemical castration with cyproterone acetate from postnatal day 60 until 360. Investigations were made on mating behavior, intermale aggression, testicular morphology, plasma testosterone level and body temperature. While controls show seasonal variations in all parameters, according to the annual cycle of sexual activity and inactivity, both, surgically and chemically castrated ferrets show throughout the year constant parameters similar to that of controls during the sexual inactive period. All investigated effects of a long-term treatment with cyproterone acetate are fully reversible within 2 years after termination of drug administration.

Animals↗
PubMed1986

Effects of cyproterone acetate and a long-acting LHRH analogue on serum lipoproteins in patients with carcinoma of the prostate.

Fasting serum lipoproteins were measured in 10 untreated patients with carcinoma of the prostate (Group I), 17 patients with non-malignant urological disorders (Group II), and 12 patients on cyproterone acetate (Group III) and 5 on a long-acting luteinizing hormone-releasing hormone (LHRH) analogue (Group IV) for at least 2 months for carcinoma of the prostate. Total high-density lipoprotein (HDL) cholesterol levels were significantly lower in patients in Group III than all the other groups. Very low-density lipoprotein (VLDL) triglyceride levels were significantly higher in patients in Group III than those in Groups II and IV. These results suggest a potentially adverse effect of cyproterone acetate, but not of the long-acting LHRH analogue, on serum lipids, which is likely to be of relevance only in younger patients.

Buserelin↗
PubMed1989

Increase in H-Y antigen-positive lymphocytes in hirsute women: effects of cyproterone acetate and estradiol treatment.

To investigate a possible relationship between lymphocyte H-Y antigen expression and plasma androgen concentrations in hirsute women, 27 hirsute women were studied. A significant increase in the percentage of H-Y-positive lymphocytes was found in both hirsute women with idiopathic hirsutism [13.4 +/- 2.9% (+/- SD); n = 15] and hirsute women with the polycystic ovary syndrome (13.0 +/- 2.8%; n = 12) compared to that in normal women (10.0 +/- 1.9%; n = 30; P less than 0.0005). Plasma testosterone and androstenedione concentrations, % H-Y+ lymphocytes, and hirsutism scores diminished during oral cyproterone acetate (50 mg/day) and percutaneous estradiol (3 mg/day) treatment. Significant correlations between % H-Y+ lymphocytes and hirsutism scores (P less than 0.001), % H-Y+ lymphocytes and plasma T concentrations (P less than 0.01) were found. We conclude that 1) women can produce H-Y antigen in the same way as men; 2) hirsutism is associated with an increase in H-Y antigen; and 3) the antiandrogen cyproterone acetate reduces H-Y antigen expression on lymphocytes.

Adult↗
PubMed1988

A reversed-phase high-performance liquid chromatographic method for the simultaneous determination of serum concentrations of cyproterone acetate and 15 beta-hydroxycyproterone acetate.

A reversed-phase high-performance liquid chromatographic method for the simultaneous determination of cyproterone acetate (CPA), 15 beta-hydroxycyproterone acetate (15 beta-OH-CPA) and cyproterone (CP) was reported. This method was specific, sensitive, precise, easy and rapid for determination of the serum concentrations of these steroids in patients receiving CPA. Although no peak corresponding to CP was observed for serum, peaks corresponding to CPA and 15 beta-OH-CPA were detected and well separated in all subjects undergoing long-term CPA therapy. In these patients, there seemed to be a dose-dependent relationship between the amount of CPA administered and the serum concentrations of these steroids, and the serum concentrations of CPA were either similar or low compared with those of 15 beta-OH-CPA. In conclusion, this simplified method is thought to be very valuable for studies on the pharmacokinetics of CPA and 15 beta-OH-CPA, and on the relationship between the CPA dosage and the therapeutic or side effects on adrenal and gonadal steroid production.

Administration, Oral↗
PubMed1979

The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men.

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.

Adult↗