cyproterone and Body-Weight

The investigators compared 2 mg cyproterone acetate (CPA) in combination with either 0.035 mg or 0.050 mg ethinyl estradiol (EE2) (Diane -35 versus Diane -50) in the treatment of acne. Both formulations of Diane were highly effective in improving acne, even in women who had been refractory to other types of medication. Cycle control with both formulations was excellent and adverse effects were generally mild and confined to the first two cycles of treatment. Mean plasma lipid levels increased with both treatments, yet most individual values remained within normal limits after one year of therapy while the LDL-cholesterol/HDL-cholesterol ratio was stable throughout the study period. Plasma testosterone and DHEA-S levels paralleled the decline in the clinical severity of the acne. There was no loss of clinical effectiveness with Diane -35 and it provided the advantage of a 30% decrease in the amount of estrogen.

Topics: Acne Vulgaris; Adolescent; Adult; Amenorrhea; Analysis of Variance; Apolipoproteins; Body Height; Body Weight; Cholesterol; Cyproterone; Cyproterone Acetate; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Ethinyl Estradiol; Female; Humans; Menstrual Cycle; Testosterone; Triglycerides

We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.. In a study of low-dose oral contraceptives, it was found that the low dosage caused insignificant effects on glucose and lipid metabolism. 57 women of good health were studied and divided into 3 groups determined by the preparation given: monophasic desogestrel, monophasic cyproterone acetate, and triphasic gestodene. There was no family history of diabetes mellitus nor was there hyperlipoproteinemia in any of the women. Among the 3 groups, there were negligible differences concerning glucose and insulin levels and lipid profiles. This held true at both the beginning and concluding stages of the study. In all of the women, the insulin area/glucose area ratio was unaffected. Lipid metabolism and hyperglycemia have been linked to heart disease, and other reports have shown glucose and lipid abnormalities produced in women taking the 2 most popular progestins, norgestrel and norethindrone. Thus, the minor effects on carbohydrate and lipid metabolism found in these tests are significant.

Topics: Adult; Androgen Antagonists; Blood Glucose; Body Weight; Cholesterol; Contraceptives, Oral, Combined; Cyproterone; Cyproterone Acetate; Desogestrel; Ethinyl Estradiol; Female; Glucose Tolerance Test; Humans; Insulin; Norpregnenes; Progesterone Congeners; Random Allocation; Reference Values; Triglycerides

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.

Topics: Aged; Body Weight; Cardiovascular Diseases; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation; Time Factors

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.

Topics: Adolescent; Adult; Amenorrhea; Body Weight; Breast Diseases; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Double-Blind Method; Drug Combinations; Ethinyl Estradiol; Female; Hirsutism; Humans; Random Allocation; Time Factors

The results of a previous 4-mo study in azaserine-treated rats and BOP-treated hamsters indicated that orchiectomy inhibited pancreatic growth and development of putative preneoplastic lesions in the exocrine pancreas of rats but not hamsters. This 12-mo study was carried out to investigate the effects of orchiectomy, alone and in combination with testosterone, and of treatment with cyproterone acetate on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. Treatment started 4 mo after injection of the carcinogen. In orchiectomized rats, pancreatic wt was lower than in controls, whereas pancreatic wt of orchiectomized rats treated with testosterone was similar to that of controls. Both orchiectomy and cyproterone acetate caused a decrease in body wt gain and had an inhibitory effect on pancreatic carcinogenesis. Testosterone treatment did not influence the inhibitory effects of orchiectomy on body wt gain and on pancreatic carcinogenesis. In hamsters, neither orchiectomy, alone or in combination with testosterone, nor cyproterone acetate (CA) affected pancreatic growth or pancreatic carcinogenesis. This study indicates that testosterone plays a minor role in the development of pancreatic tumors induced in rats by azaserine but not in that of pancreatic tumors induced in hamsters by BOP.

Topics: Animals; Azaserine; Body Weight; Cricetinae; Cyproterone; Cyproterone Acetate; Growth Substances; Male; Mesocricetus; Nitrosamines; Orchiectomy; Organ Size; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Specific Pathogen-Free Organisms; Testosterone

The effects of a range of antiandrogens and antiestrogens on conflict behaviors in laboratory rats and mice are reassessed in the light of recent studies applying ethophamacological analyses (recording the full spectrum of behaviors) to such investigations. It is argued that any antihostility properties of the antiandrogen cyproterone acetate are largely a consequence of indirect actions on odor communication, whereas antiestrogens (e.g., tamoxifen and CI 680) seem to have more fundamental motivational effects in addition to communicatory actions. A detailed example of the approach is provided in which progesterone (which can be antiandrogenic) is given to rats paired in different ways. The type of pairing has a very substantial effect on the actions seen after treatment, and the ethopharmacological approach generates a better picture of antihormone effect than traditional psychopharmacological tests.

Topics: Agonistic Behavior; Androgen Antagonists; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Estrogen Antagonists; Female; Interpersonal Relations; Light; Male; Mice; Organ Size; Progesterone; Rats; Styrenes; Tamoxifen

Phenotypically altered liver foci were produced in female Wistar rats by a single dose of N-nitrosomorpholine followed by promotion with phenobarbital (PB) for 20 or 28 weeks. Then treatment was changed to either hexachlorocyclohexane (HCH), or cyproterone acetate (CPA), or nafenopin (Naf) or clofibrate (Clof), two hypolipidemic drugs. Foci were identified by a positive reaction for gamma-glutamyl-transpeptidase (GGT) and other cytological markers. HCH and CPA could substitute for PB as foci promoters; in contrast, Naf and Clof decreased expression of GGT in foci resulting in a decline of number and area of detectable foci, effects particularly pronounced with Naf. Immunohistochemical investigations of serial sections revealed that Naf also reduced expression of the altered phenotype when cytochrome P450-PB and pyruvate kinase (type L) were used as foci markers, but not when glutathione-S-transferase B (GST-B) was used. Thus, the number of foci with enhanced GST-B did not decline significantly after the change from PB to Naf treatment. Furthermore, the reduction of GGT and the decrease of foci number during Naf treatment were not associated with increased evidence of cell death by apoptosis in foci, in contrast to the situation after PB withdrawal. These findings strongly suggest that the disappearance of GGT-positive foci after Naf is due to a phenotypic change resulting in a suppression of GGT expression rather than to physical elimination of foci.

Topics: Animals; Body Weight; Carcinogens; Cell Survival; Clofibrate; Cyproterone; Cyproterone Acetate; Female; Glutathione Transferase; Hexachlorocyclohexane; Liver; Liver Neoplasms, Experimental; Nafenopin; Nitrosamines; Organ Size; Phenobarbital; Phenotype; Precancerous Conditions; Propionates; Rats; Rats, Inbred Strains

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.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aminobiphenyl Compounds; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Genitalia, Male; Male; Methylnitrosourea; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Survival Analysis; Testosterone

Forty hyperandrogenemic women were investigated in order to determine whether the source of androgen excess could be attached to a dysfunction of the ovary or the adrenal cortex with a higher degree of accuracy when both steroid-producing organs were subjected to a supposedly specific suppression test. Dexamethasone (DXM) was administered at a dose of 2 mg for 2 days. The ovary-suppression test (OST) was carried out after a combined preparation containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (EE-CPA) had been taken for 2-3 weeks. Before and after the tests, the serum levels of testosterone (T), free testosterone (fT), DHEA-S and SHBG were determined. Serum T was lowered by DXM and EE-CPA to the same degree: the latter was more effective with respect to fT. DHEA-S responded much better to DXM than to EE-CPA. The basal level of SHBG was below the lower limit of the norm in 45% of the women. This indicates that hyperandrogenemia can be associated with normal and subnormal levels of SHBG. T and/or fT were elevated in all 40 women. DHEA-S was higher than normal in only 22 of the 40. DXM normalized the DHEA-S level in all but 1 case. In another 18 women, serum T and fT remained unaffected by DXM. This indicates an ovarian source of androgen excess in these cases. The number of cases was reduced from 18 to 4 when the OST was carried out. Even though DXM and EE-CPA are not completely organ-specific in action, the combination of both suppression tests seems to allow a higher degree of discrimination to be made between an ovarian and an adrenal component of hyperandrogenemia than is possible with either test alone.

Topics: Adolescent; Adrenal Glands; Adult; Androgens; Body Mass Index; Body Weight; Cyproterone; Cyproterone Acetate; Dexamethasone; Ethinyl Estradiol; Female; Hirsutism; Humans; Oligomenorrhea; Ovary; Progesterone; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

The action of the endogenous steroid epitestosterone administered to castrated male mice substituted with testosterone propionate is manifested by reduced weight increments and a reduced relative weight of their seminal vesicles and kidneys. Epitestosterone in vitro displaces androgens from their bond with receptors in cytosol from rat prostates and markedly inhibits the testosterone transformation to the more effective androgen dihydrotestosterone. Epitestosterone can be thus defined as a true endogenous antiandrogen; to its action at the receptor level a potent inhibitory effect on 5 alpha-reductase must be added.

Topics: Androgen Antagonists; Animals; Body Weight; Castration; Cyproterone; Cyproterone Acetate; Epitestosterone; Male; Mice; Receptors, Androgen; Testosterone

Effect of three antiandrogens: cyproterone acetate (5 mg/day, sc), flutamide (5 mg/day, sc) and STS-557 (5 mg/day, po) and an estrogen, estradiol dipropionate (5 micrograms/day, sc) on some key enzymes of carbohydrate metabolism was investigated in adult rat epididymis and ventral prostate. Antiandrogens were administered for 21 days and estrogen for 14 days. All of them caused a significant decrease in the weight of epididymis, seminal vesicles and ventral prostate. A significant decrease in the specific activities of enzymes (hexokinase, phosphofructokinase, aldolase, glyceraldehyde phosphate dehydrogenase, pyruvate kinase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) occurred only in the organs of estrogen treated rats; activities of some of the enzymes were lowered also in the prostate of STS-557 treated rats. Flutamide and cyproterone acetate were ineffective in this regard. The possible factors responsible for the ineffectiveness of synthetic antiandrogens in influencing epididymal metabolism are discussed.

Topics: Androgen Antagonists; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Enzymes; Epididymis; Estradiol; Flutamide; Glycolysis; Male; Nandrolone; Organ Size; Prostate; Rats

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.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Cell Count; Chickens; Concanavalin A; Corticosterone; Cyproterone; Cyproterone Acetate; Female; Lectins; Lymphocyte Activation; Lymphocytes; Male; Organ Size; Phytohemagglutinins

We have recently described an androgen-repressed gene in the rat ventral prostate, termed TRPM-2, that appears to be involved in the processes of cell regression and programmed cell death. We have analyzed the effect of two antiandrogens currently used in the treatment of prostatic carcinoma on the induction of this gene. Cyproterone acetate (10 mg/day) and flutamide (15 mg/day), when administered to castrated rats receiving a maintenance dose of 5 alpha-dihydrotestosterone proprionate (250 micrograms/day), induce the expression of TRPM-2. Northern hybridization and dot blot analysis demonstrate that TRPM-2 steady-state levels reach a maximum on day 4 of treatment with cyproterone acetate (520 ppm) and on day 6 of treatment with flutamide (190 ppm). During this time the steady-state levels of the androgen-dependent prostate steroid-binding protein mRNA are reduced dramatically (from approximately 75,000 to 10,000 ppm), but are not eliminated even after extended treatment. Treatment with the two antiandrogens produces a substantial reduction in the organ weight/body weight ratio and RNA content of the prostate when compared to rats receiving the maintenance dose alone. These results suggest that while neither cyproterone acetate nor flutamide fully repress the androgen-dependent functions of the prostate, they do induce some of the androgen-repressed sequences in the prostate that have been implicated in the process of cell death.

Topics: Androgen Antagonists; Androgens; Animals; Blotting, Northern; Body Weight; Cell Survival; Cell-Free System; Cyproterone; Cyproterone Acetate; Flutamide; Gene Expression Regulation; Male; Orchiectomy; Organ Size; Prostate; Protein Biosynthesis; Rats; Rats, Inbred Strains; RNA

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.

Topics: Animals; Body Weight; Cercopithecidae; Cholesterol; Contraceptive Agents, Male; Cyproterone; Cyproterone Acetate; Glycogen; Libido; Lipids; Male; Phosphoric Monoester Hydrolases; Testis; Testosterone

The influence of the graded doses of progesterone and progestational antiandrogen, cyproterone acetate, is studied on the vaginal cycles, follicular dynamics and steroidogenic potential of the ovaries and adrenal glands in neonatally androgenised rats with persistent vaginal estrous. Of the different doses of progesterone, 0.5 mg progesterone/day is found to reinstate more or less normal vaginal cycles. None of the doses of progesterone and CPA induced ovulation in cystic ovaries and hence the vaginal cycles thus reinstated are not the reflection of ovarian cycles and the diestrous smear is not an indication of functional CL in these ovaries. The treatment of progesterone and CPA brought about degenerative changes in the antral follicles above stage IV and in cystic type I follicles. It mobilised the growth of type 0 follicles up to the early antral stage of type III, thereby indicating the presence of the negative feedback of progestational steroids on FSH secretion in PVE rats. The minimum change in the activity of carbohydrate metabolising enzymes and the steroid dehydrogenases in the ovaries subsequent to the treatment with especially the higher doses of progesterone, and CPA suggests the absence of any impact on LH secretion, albeit indirect. There was a marked reduction in the steroidogenic potential in the adrenal glands of the CPA treated rats; however, it did not show any positive impact on the structure of the polycystic ovary.

Topics: Adrenal Glands; Animals; Animals, Newborn; Body Weight; Cyproterone; Cyproterone Acetate; Estrus; Female; Glucosephosphate Dehydrogenase; Histocytochemistry; Hydroxysteroid Dehydrogenases; Luteinizing Hormone; Organ Size; Ovary; Progesterone; Rats; Succinate Dehydrogenase; Testosterone

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

Topics: Animals; Azoxymethane; Binding Sites; Body Weight; Colon; Colonic Neoplasms; Cyproterone; Cyproterone Acetate; Cytosol; Estrenes; Kinetics; Male; Metribolone; Orchiectomy; Rats; Rats, Inbred Strains; Receptors, Androgen; Rectal Neoplasms; Testosterone

Male mice were injected daily with cyproterone acetate for 10 consecutive days during one of the four following periods: 1-10 days, 11-20 days, 21-30 days or 31-40 days. At all stages studied cyproterone acetate caused a significant reduction in the relative weights of epididymis, vas deferens, preputial gland and seminal vesicle in males killed 24 h after the last injection; the androgen content (testosterone + dihydrotestosterone) of the accessory sex organs was also reduced but the differences were not always significant. Cyproterone acetate treatment from 1 to 10 days resulted in a definitive reduction in the relative weights of all accessory sex organs studied and when injected from 11 to 20 days in epididymis and vas deferens. When cyproterone acetate was injected after 20 days of age, the inhibition of sexual organ weights was reversible and at adulthood organs were normally developed. Cyproterone acetate treatment induced a high percentage of infertile males only when injected from 1 to 10 days. Spermatogenesis, androgen levels in plasma and accessory sex organs, and sexual behaviour were not affected in sterile males. These results suggest that the functional development of accessory sex organs can be permanently affected by short-term neonatal exposure to endogenous androgens.

Topics: Age Factors; Animals; Animals, Newborn; Body Weight; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Fertility; Genitalia, Male; Male; Mice; Mice, Inbred Strains; Organ Size; Testosterone

Cyproterone acetate was administered every 2 days from 1 to 39 days of age to male mice which were killed 24 h or 20 days after the last injection. Cyproterone acetate caused a significant reduction in the relative weights of the epididymis, vas deferens, seminal vesicle and preputial gland, which was still evident at 60 days after birth. Testicular and epididymal androgens (testosterone and dihydrotestosterone) and circulating LH and FSH concentrations were equal to or higher than those of controls at 60 days. Cyproterone acetate did not inhibit spermatogenesis but all males were infertile. The results suggest that the peripheral effects of testosterone are necessary, during early stages of sexual maturation, in order to obtain subsequent full development of the accessory sex organs.

Topics: Aging; Androgen Antagonists; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Epididymis; Fertility; Follicle Stimulating Hormone; Genitalia, Male; Male; Mice; Mice, Inbred Strains; Organ Size; Sexual Maturation; Testis; Testosterone

The aggressive behavior of male rats treated chronically with cyproterone acetate was measured following electric footshock. Shock elicited fighting behavior and body weight was recorded once every week for 4 weeks. The level of plasma testosterone, brain 5-HT and 5-HIAA and weight of testes were measured 24 hours after the last injection. No significant change was observed in the level of testosterone or brain 5-HT and 5-HIAA. A trend towards an increase in plasma testosterone and shock elicited fighting in rats treated with a higher dose of CA (10 mg/kg) may be indicative of some androgenic property of CA. On the other hand a slower gain in the body weight and a significant reduction in the testes weight of CA treated rats corroborate the well known antiandrogen property of this steroid. The balance of these androgenic and antiandrogenic properties of CA may account for the absence of significant changes in behavioral and biochemical measures.

Topics: Aggression; Animals; Body Weight; Brain Chemistry; Cyproterone; Cyproterone Acetate; Electroshock; Humans; Hydroxyindoleacetic Acid; Male; Organ Size; Rats; Rats, Inbred Strains; Serotonin; Testis; Testosterone

Topics: Animals; Body Weight; Cyproterone; Cyproterone Acetate; Ejaculation; Female; Grooming; Macaca; Male; Sexual Behavior, Animal

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female rats have been investigated. This agent causes reduction in ovarian weights indicative of suppression of pituitary gonadotrophins. Oestrogenic nature of cyproterone acetate was investigated in intact and ovariectomized animals taking uterine weight, vaginal keratinization and other oestrogen sensitive biochemical parameters. Cyproterone acetate in ovariectomized animals induced vaginal keratinization, increase in uterine weight and uterine protein, RNA, glycogen and sialic acid contents. These effects were parallel to the effect of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity cyproterone acetate. The histological and biochemical parameters lead to the conclusion that cyproterone acetate possessed antifertility property due to its inherent oestrogenic nature.

Topics: Adrenal Glands; Animals; Body Weight; Castration; Cyproterone; Estradiol; Female; Fertility; Glycogen; Organ Size; Ovary; Proteins; Rats; RNA; Sialic Acids; Uterus; Vagina

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female rats have been investigated. This agent caused reduction of ovarian weights indicative of suppression of pituitary gonadotrophins. Oestrogenic nature of cyproterone acetate was investigated in intact and ovariectomized rats taking uterine weight and vaginal keratinization as an index of oestrogenicity. Cyproterone acetate in ovariectomized animals induced vaginal keratinization and increased the uterine weights. These effects were parallel to the effect of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity of cyproterone acetate. We may conclude that the above compound caused antifertility effects due to its oestrogenic nature at the dose level of 2 mg/alternate day in rats when the compound was administered subcutaneously.

Topics: Animals; Atrophy; Body Weight; Castration; Cyproterone; Estradiol; Female; Fertility; Genitalia, Female; Hyperplasia; Hypertrophy; Keratins; Organ Size; Ovary; Rats; Reproduction; Uterus; Vagina

The effects of cyproterone acetate (CA) on fertility of spermatozoa and rouleau formation were investigated in male guinea pigs. Twelve of 15 matings during CA treatment resulted in pregnancy even when rouleaux were absent in ejaculates, indicating that the rouleau condition is not necessary for the fertilizing ability of guinea pig spermatozoa. Examination of epididymides and vasa deferentia revealed that rouleaux diminished progressively with treatment time and were absent in the excurrent ducts of all males during the eighth and ninth weeks of treatment. Following a latent period after treatment, rouleaux were first noted in a specific epididymal region and were present throughout the distal excurrent ducts and ejaculates by 6 wk posttreatment. This sequence of rouleau loss and reappearance in the excurrent ducts suggests that rouleau formation is dependent on a regional epididymal influence that requires androgens. Spermatogenesis was not arrested; however, seminal vesicle and body weights were reduced in treated males.

Topics: Animals; Body Weight; Cell Aggregation; Cyproterone; Fertility; Guinea Pigs; Male; Organ Size; Seminal Vesicles; Spermatogenesis; Spermatozoa; Time Factors

Topics: Androgen Antagonists; Androgens; Animals; Body Weight; Castration; Cyproterone; Eating; Estrogen Antagonists; Estrogens; Hydroxytestosterones; Male; Nafoxidine; Rats; Time Factors

The effectiveness of therapy with cyproterone acetate and ethinyl estradiol was studied in 103 women. Acne and seborrhea responded best with 91.7 and 93.3% respectively, including complete and partial therapeutic success. For hirsutism complete remission and partial improvement were found in 75.3% of the treated women. Under therapy, body weight did not change in 51.9%, while 24.7% of the patients gained weight and 23.4% lost weight. The cycle length remained normal after therapy in 35.8%. Normalization or improvement was found in 54.7%. In 6.3% no improvement was noted after therapy and in 3.2% cycle irregularity developed in women with previous undisturbed pattern. According to BBT, improvement of the functional capacity of the reproductive system was found in 32.9% of the patients. Only 3% of the women studied demonstrated a deterioration. The 17-ketosteroid excretion was diminished in 35.3% after therapy and remained unchanged in 64.7%. The therapeutic regimen used for the study was well tolerated and good cycle control was obtained.

Topics: 17-Ketosteroids; Acne Vulgaris; Adolescent; Adult; Body Temperature; Body Weight; Cyproterone; Dermatitis, Seborrheic; Ethinyl Estradiol; Female; Hirsutism; Humans; Menstruation; Menstruation Disturbances; Remission, Spontaneous

Topics: Animals; Body Weight; Cyproterone; Female; Fetus; Genitalia, Female; Genitalia, Male; Male; Mice; Pregnancy

Topics: Animals; Body Weight; Chickens; Comb and Wattles; Cyproterone; Female; Growth Inhibitors; Male; Mullerian Ducts; Spermatozoa; Starvation; Testis; Transplantation, Homologous

Topics: Adrenal Glands; Animals; Body Weight; Cricetinae; Cyproterone; Estrogens; Female; Gonadal Steroid Hormones; Male; Mesocricetus; Organ Size; Sex Factors; Testosterone

Topics: Androgen Antagonists; Androstanes; Animals; Body Weight; Castration; Cyproterone; Drug Evaluation, Preclinical; Male; Mice; Organ Size; Organ Specificity; Structure-Activity Relationship; Testosterone Congeners

Administration for different doses of cyproterone acetate (CPA) to male hamsters for 5 weeks slows down the growth of the adrenals and the increase in body weight. This effect is still present 4 weeks after cessation of CPA treatment, though some recovery can be seen. Histological and histometrical evaluations confirm an atrophy of the adrenal, particularly in the zona fasciculata and in higher doses also in the zona reticularis. After operative castration it is the zona reticularis which shows the most marked atrophic changes. It is therefore concluded, that CPA possesses besides its anti-androgenic properties an inhibiting corticoid-like effect on the adreno-pituitary feed-back mechanism.

Topics: Adrenal Glands; Animals; Body Weight; Cricetinae; Cyproterone; Feedback; Male; Organ Size; Pituitary-Adrenal System

Twenty-nine children (23 girls, 6 boys) with precocious puberty were treated with cyproterone acetate for various periods of time ranging from 6 months to 3 years 4 months. They received an oral dose ranging from 70-150 mg/m2 per day, or an intramuscular depot injection once a fortnight or once a month at a dose ranging from 107-230 mg/m2. Both forms of therapy were found to suppress the signs of sexual maturation, but the oral form proved to be superior. Only the younger patients with a bone age under 11 years showed a beneficial effect upon linear growth and bone maturation. No side effects were noted, but additional advantageous effects upon behaviour and sociability were. It is concluded that at present cyproterone acetate by mouth is the drug of choice in the treatment of precocious puberty. The treatment should be initiated as early as possible to attain maximum benefit.

Topics: Administration, Oral; Adolescent; Behavior; Body Weight; Bone Development; Child; Child, Preschool; Cyproterone; Female; Growth; Humans; Injections, Intramuscular; Male; Puberty, Precocious; Skinfold Thickness

The effect of castration, androgen and antiandrogen treatment on bone protein content of femoral diaphyses of male mice was investigated. Castration as well as administration of 2.5 mg of cyproterone acetate for 21 days reduced significantly the protein content of the bone. Testosterone fully compensated the bone protein depletion seen in castrates. Simultaneous administration of both cyproterone acetate and testosterone to castrates blocked the testosterone action. The data show that the mice bone matrix is a highly androgen dependent tissue.

Topics: Animals; Body Weight; Bone and Bones; Castration; Cyproterone; Male; Mice; Proteins; Seminal Vesicles; Testosterone

A specific antiandrogenic steroid cyproterone acetate was administered daily to mice of three different inbred strains starting from the day of birth until the age of 30 days. The total dose per mouse was 17.2 mg. This treatment resulted in developmental retardation which was manifested in a number of ways: at the age of 30 days, the weight of the body was well as spleen, testes and particularly thymus was significantly reduced; histologically, the normal proportion of the red and white pulp in the spleen was changes; spermatogenesis (but not oogenesis) was markedly retarded corresponding to the age of 12-15 days in normal males; also skin displayed a persisting immaturity as reflected by an abundance of mast cells. Minor signs of toxic changes were seen in the liver. Skin grafts from CA-pretreated donors had a subnormal immunogenicity; when transplanted across the MSA-barrier, they survived significantly longer than control grafts and about 23% took. Significantly prolonged survival was also observed with H-3 incompatible skin grafts from CA-pretreated donors, particularly from male donors. Across the barrier dicated, but did not reach a level of significance. The present study extends our previous observations concerning the androgen dependence of a normal immunogenic expression of H-antigens. The antiandrogenic effect of CA is comparable to the more complex effect of neonatal orchiectomy in terms of the subnormal immunogeneity of MSA-incompatible skin grafts from 30-day-old males which seems to be arrated at a stage typical for 1-2-day-old normal males.

Topics: Androgen Antagonists; Animals; Animals, Newborn; Antibody Formation; Body Weight; Cyproterone; Epitopes; Female; Graft vs Host Reaction; Growth; Histocompatibility Antigens; Male; Mice; Mice, Inbred C57BL; Organ Size; Skin Transplantation; Spermatogenesis; Transplantation, Homologous

The loss of endogenous testosterone in castrated male mice leads to a marked decrease in seminal vesicle and kidney tissue weight. 21 days' administration of exogenous testosterone abolished the effect of castration on the seminal vesicles and kidney tissue. The antiandrogen cyproterone acetate produced significant changes in the target tissue for androgens, i.e. in the seminal vesicles. In every case it blocked the action of both exogenous and endogenous testosterone on the seminal vesicles, but failed to block the "renotropic" action of testosterone, expressed as relative kidney weight. Contrary to its effect on the seminal vesicles, it did not influence relative kidney weight in normal animals. It likewise did not block the effect of exogenous testosterone on kidney tissue. The mechanism of the action of cyproterone acetate in androgen-dependent tissues is known to consist in inhibition of androgen binding to specific cell receptors in the target tissues. Some of the specific androgen receptors in mouse kidney are evidently different in character from those in the accessary sex glands, that being the reason why cyproterone acetate has an antiandrogenic, but not an antirenotropic effect. In agreement with experiments on rats, adrenal weight also decreases in mice after the administration of cyproterone acetate.

Topics: Animals; Body Weight; Castration; Cyproterone; Kidney; Male; Mice; Organ Size; Seminal Vesicles; Testosterone

In the first experiment gonadectomized male rats were injected daily with various combinations of vehicle (V), estradiol benzoate (E), dihydrotestosterone (D) and/or the anti-androgen cyproterone acetate (CA). The eight treatment combinations consisted of V, E, D, CA, E + D, E + CA, D + CA and E + D + CA. Only those males treated with both E and D were found to display ejaculations. Concurrent treatment with CA completely blocked ejaculatory behavior and it significantly reduced both mount and intromission frequencies. Examination of peripheral androgen target tissues indicated that following stimulation with D, CA effectively reduced seminal vesicle and penile weights, and penile lengths, but it did not reduce penile spines. In the second experiment gonadectomized female rats were treated with two daily injections of E, E + CA or E + the anti-estrogen CI-628. A second set of gonadectomized females received three daily injections of testosterone (T), T + CA or T + CI-628. On the day after completion of these injections all females received progesterone and were tested for sexual receptivity three hours later. Both E and T treated females were found to display the lordotic posture in response to mounting stimulation while both CI-628 and CA were found to block this behavior. In E treated females, CI-628 and CA were also found to reduce uterine weight. Thus, CA was shown to have anti-estrogenic as well as anti-androgenic properties. These results were discussed in terms of the aromatization and 5alpha reduction theories of testosterone action in sexual behavior.

Topics: Androgens; Animals; Body Weight; Castration; Cyproterone; Dihydrotestosterone; Estradiol; Estrogens; Female; Male; Nitromifene; Organ Size; Penis; Rats; Seminal Vesicles; Sexual Behavior, Animal; Testosterone; Uterus

Cyproterone and cyproterone acetate exert the corticoid-like effect on the adrenal and spleen weight in the mice. When compared with prednisone, cyproterone acetate has approximately 1/5 of the corticoid potency of prednisone, expressed by the decrease of the spleen weight.

Topics: Adrenal Glands; Animals; Body Weight; Cyproterone; Male; Mice; Organ Size; Prednisone; Seminal Vesicles; Spleen; Testosterone

Topics: Administration, Oral; Animals; Body Weight; Castration; Cyproterone; Decidua; Ethynodiol Diacetate; Female; Injections, Subcutaneous; Norethynodrel; Norgestrel; Ovary; Pregnancy; Progesterone; Progestins; Rats; Rats, Inbred Strains; Urinary Bladder; Uterine Neoplasms; Uterus; Vagina

Topics: Adrenal Glands; Adrenalectomy; Animals; Behavior, Animal; Body Height; Body Weight; Castration; Cattle; Cyproterone; Feeding Behavior; Female; Growth; Growth Hormone; Male; Organ Size; Organ Specificity; Ovary; Pituitary Gland; Rats; Sex Factors; Testis

Topics: Animals; Body Weight; Cyproterone; Depression, Chemical; Male; Mice; Organ Size; Penis; Pheromones; Prostate; Sebaceous Glands; Sexual Behavior, Animal; Urine

Topics: Androsterone; Body Height; Body Weight; Bone Development; Child; Child, Preschool; Cyproterone; Dehydroepiandrosterone; Etiocholanolone; Female; Humans; Male; Prognosis; Puberty, Precocious; Testosterone; Time Factors

Topics: Androgen Antagonists; Animals; Body Weight; Cyproterone; Enzyme Induction; Female; Hexobarbital; Hypophysectomy; Liver; Microscopy; Microscopy, Electron; Organ Size; Paralysis; Pituitary Gland; Pregnadienes; Rats; Sleep; Time Factors; Zoxazolamine

Topics: Androgen Antagonists; Androstanes; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Castration; Collagen; Cyproterone; Elastin; Hypertension; Male; Muscle, Smooth; Organ Size; Proteins; Rats

Topics: Animals; Body Weight; Cyproterone; Karyometry; Leydig Cells; Male; Organ Size; Prostate; Rats; Seminal Vesicles; Testis

Topics: Androgen Antagonists; Animals; Arginase; Body Weight; Castration; Cyclophosphamide; Cyproterone; Disease Models, Animal; DNA; Dogs; Drug Evaluation, Preclinical; Fluorouracil; Humans; Male; Organ Size; Oxidoreductases; Prostate; Prostatic Neoplasms; Rats

Topics: Acetates; Animals; Body Height; Body Weight; Bone Development; Castration; Cyproterone; Drug Synergism; Epiphyses; Estradiol; Female; Femur; Forelimb; Metacarpus; Metatarsus; Osteogenesis; Propionates; Rats; Testosterone; Tibia; Time Factors

Topics: Adult; Aged; Androgen Antagonists; Body Weight; Cyproterone; Diet; Dose-Response Relationship, Drug; Ethinyl Estradiol; Female; Hirsutism; Humans; Male; Menstruation Disturbances; Middle Aged; Nitrogen; Pregnadienes; Prostatic Neoplasms