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PubMedDate not supplied

Cyproterone acetate induced changes in the behaviour of hydroxysteroid dehydrogenases in rat Leydig cells during perinatal development.

The influence of cyproterone acetate (CA) upon the behaviour of hydroxysteroid dehydrogenases (HSDH) in the Wistar rat Leydig cells was investigated during the perinatal phase with the help of enzymhistochemical cum morphometrical techniques. The pregnant rats as well as their offsprings were injected with CA (dosage: 35 mg/kg body wt) sc, daily from 14 fetal day upto 31 postnatal day (p.n.d.). The animals were killed on 5, 20, and 32 p.n.d.; the enzymhistochemical reactions for 3-beta-HSDH, 11-beta-HSDH, 17-HSDH and 3-alpha-HSDH were performed in the cryostat sections of the testis, and the morphometric evaluation of HSDH positive Leydig cells was carried out. On 5 p.n.d. the activity of 17-beta-HSDH was slightly impaired in the intertubular Leydig cells of the CA treated animals. On 20 p.n.d., CA prevented nearly completely the HSDH activity in the newsly built peritubular Leydig cells; the activities of 3-beta-HSDH, 17-beta-HSDH, and 3-alpha-HSDH resided mainly in the intertubular Leydig cells. On 32 p.n.d. the HSDH activities in the Leydig cells were observed in the control as well as in treated animals. It seems that the differentiation of peritubular Leydig cells, and thereby the steroid production, is delayed by CA, but not entirely blocked.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Lectin staining of rat testis and epididymis: effect of cyproterone acetate and testosterone.

Control and castrated (C) adult rats were treated with cyproterone acetate (CA), testosterone (T) or their combination (CA + T) for 15 days and the affinity of the testicular and epididymal tissue for seven rhodamine-conjugated lectins was analysed in fluorescence microscopy. In the testis CA caused the appearance of degenerating cells in the basal part of the seminiferous epithelium. These cells (spermatogonia, early spermatocytes) appear to be the most vulnerable germinal cells to anti-androgen treatment and this effect could be prevented by simultaneous administration of T. Castration caused a marked reduction in lectin staining of principal and light cells of distal caput (Dcp) and distal cauda (Dcd) epididymidis accompanied by the disappearance of the intratubular sperm mass. In castrated animals CA caused a moderate and T as well as CA + T a marked increase in the stainability of these cells and the appearance of homogeneous secretory material in the tubules. This material gave moderate or strong affinity for most of the lectins. Some minor differences were found in the staining pattern of the cells and the secretory material in Dcp and Dcd as well as after different treatments. This is consistent with local and qualitative differences in the epididymal secretory and absorptive activity, which can be further modified by the hormonal milieu.

Animals↗
PubMed1990

Effects of cyproterone acetate and testosterone treatments on some physical parameters, angiotensin converting enzyme activity and fertilizing ability of spermatozoa of domestic cocks (Gallus domesticus).

Healthy adult cocks were administered through the intramuscular route with 1 or 15 mg cyproterone acetate (CyA)/kg b. wt. or testosterone at the rate of 1.5 mg/kg b. wt. daily for a period of 25 days. High doses of CyA and testosterone caused severe suppression (P less than 0.01) of semen volume, sperm concentration, sperm motility and angiotensin converting enzyme activity (ACE EC 3.4.15.1). Fertilizing ability of spermatozoa was also reduced drastically at the end of treatment period. No loss of sexual behaviour was observed in treated birds as compared to controls. Recovery in all parameters from deleterious effects of these drugs was rapid after cessation of treatment. Lower doses of CyA did not affect the parameters of semen. The results are discussed in relation to the possible mechanism of action of CyA and testosterone.

Animals↗
PubMed1991

Severe hepatocellular dysfunction following cyproterone acetate therapy.

Cyproterone acetate (CPA) is a widely used drug in the treatment of advanced prostatic carcinoma. Although it is generally well tolerated, liver toxicity has been recognised as a complication of long-term use. We report 3 patients with severe hepatocellular damage due to CPA therapy, 2 with fatal fulminant hepatitis.

Aged↗
PubMed1987

Cyproterone acetate, an alternative progestogen in postmenopausal hormone replacement therapy? Effects on serum lipids and lipoproteins.

Serum lipids and lipoproteins were studied in 76 healthy postmenopausal women treated for 1 year with either oestradiol valerate sequentially combined with the anti-androgenic progestogen cyproterone acetate (CPA) or placebo. The women were examined every 3 months between days 18 and 21 of the tablet cycle, where the progestogen had been added to the oestrogen for at least 6 days. Combined oestrogen-CPA therapy resulted in significantly reduced levels of total serum cholesterol and LDL-cholesterol at all examinations, but serum triglycerides and HDL-cholesterol levels were similar in the two groups. Total serum cholesterol and LDL-cholesterol were reduced by approximately 5% (P less than 0.01) and 8% (P less than 0.01), respectively, after 1 year of combined oestrogen-CPA therapy in comparison with both the initial values and the placebo group but serum triglycerides and HDL-cholesterol levels were unchanged in both groups.

Androgen Antagonists↗
PubMed1985

Motor responses of cyproterone acetate-treated rat vas deferens to electrical field stimulation, noradrenaline and barium chloride.

The effect of cyproterone acetate (CA) was studied on the autonomic transmission and smooth muscle function of the rat vas deferens. In the CA-treated vas deferens, the endogenously released noradrenaline (NA) in response to electrical field stimulation or exogenously administered NA produced rhythmic contractions (lacking a tonic component) which were abolished by prazosin - a preferential postjunctional alpha-adrenoceptor blocker. The biphasic nature of the nonadrenergic response elicited on electrical field stimulation in CA-treated rats remained unaltered. Like in controls, yohimbine potentiated this response thereby demonstrating the presence of functional presynaptic alpha-adrenoceptors (inhibitory in nature). The postjunctional alteration on the membrane function appears to be specific to adrenergic stimulation alone, since both tonic and phasic components were demonstrated in the responses resulting from nonadrenergic stimulation or those produced by barium chloride.

Animals↗
PubMed1984

Effects of cyproterone acetate on adrenal steroidogenesis in vitro.

The effects of cyproterone acetate (CA) on steroidogenesis in isolated guinea-pig adrenal cells have been investigated by measuring the production of cortisol, its immediate precursors (11-deoxycortisol and 17-hydroxyprogesterone), and adrenal androgens (delta 4-androstenedione and dehydroepiandrosterone). Used at a dose of 2 micrograms/ml, CA provoked a sharp drop in the production of cortisol, aldosterone and 11-deoxycortisol. By contrast, 17-hydroxyprogesterone, delta 4-androstenedione and dehydroepiandrosterone were increased, which suggests that 21-hydroxylase activity is inhibited. With concentrations above 2 micrograms/ml CA, it would seem to be the 3-beta-ol-dehydrogenase-delta 4,5-isomerase complex that is affected, since dehydroepiandrosterone exhibited a sudden increase, whereas 17-hydroxyprogesterone and delta 4-androstenedione showed a relative decrease. The enzymatic system or systems involved therefore appear to be linked to the concentration of CA used but, whatever the case, the drop in cortisol production is accompanied by a decrease in aldosterone and an increase in adrenal androgen levels.

Adrenal Cortex Hormones↗
PubMed1987

Comparative effects of cyproterone acetate or a long-acting LHRH agonist in polycystic ovarian disease.

A randomized cross-over study was done to compare the therapeutic efficacy of cyproterone acetate (CPA, 50 mg/day orally) and a depot preparation of the LHRH superagonist (D-Trp6 LHRH 3 mg i.m. once a month) in 10 patients with polycystic ovarian disease (PCO). The two treatment periods were separated by 6 months. Both treatments resulted in marked clinical improvement. In response to CPA treatment, basal plasma gonadotropin, estradiol, estrone, testosterone and androstenedione levels significantly decreased. In response to D-Trp6 LHRH, both basal and stimulated gonadotropin levels were completely suppressed after 3 weeks of treatment. After initial elevation on day 2, plasma ovarian steroid levels fell into the castrate range, without any change in dehydroepiandrosterone sulfate levels. Urinary 3 alpha-androstanediol excretion decreased significantly. In patients with PCO, LHRH-A induced more complete gonadotropin inhibition than did CPA. However, following cessation of either therapy, the disease rapidly recurred.

Adult↗
PubMed1991

Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature.

To evaluate the effect of cyproterone acetate (CA) on the renin-angiotensin-aldosterone axis, we measured the plasma active, inactive and total renin concentrations (PARC, PIRC and PTRC) during and after CA treatment in patients with precocious puberty and genetic short stature. CA was administered at a daily dose of 150-170 mg/m2 in all subjects. PARC and PTRC were measured by immunoradiometric assays. During CA treatment, PARC, PIRC, PTRC and the PARC/PTRC ratio were significantly decreased. The plasma renin activity, measured by enzymatic assay, and the plasma aldosterone concentration were also decreased. After CA discontinuation, all of these were increased immediately along normal ranges. PARC closely correlated with plasma renin activity. These results suggest that CA produces mineralocorticoid action and suppresses the production and activation of renin.

Androgen Antagonists↗
PubMed1986

Response of male acne to antiandrogen therapy with cyproterone acetate.

The antiandrogen cyproterone acetate, which is known to suppress sebum production, but is not a standard therapy, was given in combination with tetracycline to 63 young unmarried men who had failed to respond to 6 months' tetracycline therapy alone. Fifty-seven patients responded and the mean time to clearance was 5.2 months' therapy. The main side effects were nodular sub-nipple breast swellings, which occurred in 13 cases (21%). Such side effects were reversible and cleared after 3-4 months following cessation of therapy. Eighty-eight percent of patients relapsed within 3 months of discontinuing therapy.

Acne Vulgaris↗
PubMed1980

Effects of cyproterone acetate on experimentally induced canine prostatic hyperplasia. A morphological and histochemical study.

The effect of 3 alpha-androstanediol (3 alpha-diol), 17 beta-estradiol (E2) and cyproterone acetate (CA) on prostates in castrated beagle dogs were investigated by histological and histochemical examinations. A significant increase of prostatic weight occurred after 6 months' treatment with 3 alpha-diol alone and in combination with E2. Histologically and histochemically, two different types of prostatic enlargement were observed: first, administration of 3 alpha-diol resulted in diffuse glandular hyperplasia with replacement of functional activity monitored by strongly positive reactions for acid phosphatase, aminopeptidase and zinc. Second, 3 alpha-diol plus E2 produced stratified squamous metaplasia with cystic lumina and loss of the typical morphological structure. These glands showed negative reactions for acid phosphatase, aminopeptidase and zinc. In both types of prostatic hyperplasia CA abolished epithelial or metaplastic proliferation and induced atrophy of glandular epithelium. In estrogenized dogs activation of the fibromuscular stroma was obvious. CA prevented prostatic hyperplasia by atrophying epithelial effects.

Acid Phosphatase↗
PubMed1991

Treatment of symptomatic metastatic prostatic cancer with cyproterone acetate versus orchiectomy: a prospective randomized trial.

During a 2-year period, 37 patients with symptomatic metastatic prostatic cancer were included in a prospective randomized phase-III trial. Nineteen patients were randomized to subcapsular orchiectomy, and 18 to cyproterone acetate (CPA) treatment with a dose of 50 mg b.i.d. The median age of the patients was 74 years (range 48-88 years), with no differences between the treatment groups. At 3, 6, and 12 months after initiation of the therapy and then every 6 months, patients were clinically and biochemically examined, and isotope scans and X-rays were performed. All patients were followed until death. Relief from symptoms was found following 3 months of treatment in 70.6% (95% confidence limits = 44.0-89.7%) of the patients treated with CPA, and in 83.3% (95% confidence limits = 58.6-96.4%) of the orchiectomized patients. The median time to relapse was 9 months in the CPA group, and 11 months in the orchiectomy group (p greater than 0.05). The median survival time was 13 months, with no differences between the groups. The treatment of advanced prostatic cancer with CPA is found to be a valuable alternative to orchiectomy.

Adenocarcinoma↗
PubMed1990

Advanced prostatic cancer: clinical and hormonal response to flutamide in patients pretreated with LHRH analogue and cyproterone acetate.

The aim of the present investigation was to establish whether in advanced prostatic carcinoma in relapse treated with LHRH analogues combined with cyproterone acetate (CPA), substitution of this antiandrogen with another compound such as flutamide (FLU) might lead to further subjective and objective improvement. The present randomized study was carried out on 100 patients in relapse treated with long acting LHRH analogue + CPA: 52 patients were submitted to combination therapy with FLU, whilst the remaining 48 cases continued with CPA treatment. Plasma levels of gonadotropin FSH-LH, androstenedione and dehydroepiandrosterone sulphate were significantly reduced by both treatments, testosterone fell to castration values, but prolactin showed no change. Progress of the disease was confirmed in all the patients who continued with CPA treatment with a median survival rate of 9.3 +/- 2 months from the start of the second cycle of CPA. In the FLU-treated group, the overall objective response differed significantly in relation to the stage of the disease. In fact, in stage D2, the response was poor with a median survival of 12 +/- 2 months, which is almost comparable to that in the CPA group. In stage D1, a clinical improvement, even if of short duration, was observed in almost 50% of the cases with a median survival of 18 +/- 3 months. Good results were also obtained in undifferentiated tumours, FLU probably acting as an antimitotic agent. Moreover, FLU also exerted an analgesic effect, with relief of bone pain in 65% of the cases in stage D2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Incidental prostatic carcinoma: four-year follow-up after treatment with cyproterone acetate.

This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.

Aged↗
PubMed1990

Zoladex vs. Zoladex plus cyproterone acetate in the treatment of advanced prostatic cancer: a multicenter Italian study.

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1986

Cyproterone acetate lead-in prevents initial rise of serum testosterone induced by luteinizing hormone-releasing hormone analogs in the treatment of metastatic carcinoma of the prostate.

Luteinizing hormone-releasing hormone (LH-RH) analogs are an effective treatment of metastatic carcinoma of the prostate. However, they induce an initial rise in serum testosterone responsible for 10-30% of diseases flares. The efficacy of the antiandrogen cyproterone acetate (CPA) was tested in 15 patients with metastatic carcinoma of the prostate. 10 patients were given 100 mg CPA t.i.d. from day 1 to 14 in association with the LH-RH analog Buserelin, 500 micrograms t.i.d., from day 7 to 14.5 patients were given CPA and Buserelin at the same doses from day 1 to 7. Serum testosterone determinations were obtained on days 1-7, 8, 11 and 14, at 08.00 h, and on days 8, 11, 1 h after each analog injection in group 1, and on days 1, 4 and 7 at 08.00 h and 1 h after each analog injection in group 2. All the patients were then treated by orchidectomy. Pretreatment with CPA blunted the initial rise of testosterone which never rose above pretreatment levels. Simultaneous treatment had no demonstrable effects on the rise of serum testosterone. It is concluded that pretreatment with CPA allows a safer use of LH-RH analogs in the treatment of metastatic carcinoma of the prostate.

Aged↗
PubMed1987

Sadistic homosexual pedophilia: treatment with cyproterone acetate: a single case study.

This single case study demonstrates the effects of antiandrogen treatment on a subject with a very serious sexual deviation and a poor prognosis. It assesses the effects of cyproterone acetate (CPA) on an individual with a serious chronic organic brain syndrome combined with sadistic homosexual pedophilia. Furthermore, this individual had failed to respond to a behavioural treatment program and long-term milieu therapy. Finally, this case study is the first report of CPA differentially affecting penile responses to deviant and non-deviant stimuli.

Adult↗