SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
In a male anti-fertility study 7 volunteers received the anti-androgen cyproterone acetate (5 or 10 mg daily) orally in a paired study. A significant reduction in serum-cholesterol and LDL-cholesterol, and a significant increase in the intravenous-fat-tolerance-test (IVFTT) was observed. Thus low doses of cyproterone acetate reduced the serum testosterone concentration and some of the atherosclerotic risk factors.
Nine healthy men were treated with a daily dose of 5 or 10 mg of the anti-androgen cyproterone acetate. Platelet aggregability was increased in 6 of 9 men; fibrinolytic activity decreased in 7 of 7 and the fibrinolytic capacity decreased in 5 of 7 volunteers. We conclude that platelet aggregability, fibrinolytic activity and capacity may be modified by anti-androgen treatment and therefore attention should be paid to the coagulation parameters when cyproterone acetate is used.
The metabolism of (4-14C)4-androstene-3,17-dione, (4-14C)5alpha-androstane-3alpha, 17beta-diol and (1,2-3H)5alpha-androstane-3alpha, 17beta-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of (4-14C)4-androstene-3,17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changes in a direction characteristic of female rats: 5alpha-reductase active on 4-androstene-3,17-dione increased in activity whereas 3beta- and 17alpha-hydroxysteroid reductases and 6beta- and 16alpha-hydroxylases active on 4-androstene-3,17-dione and 2alpha-, 2beta- and 18-hydroxylases active on 5alpha-androstane-3alpha,17beta-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3alpha- and 17beta-hydroxysteroid reductases active on 4-androstene-3,17-dione and 7alpha-hydroxylase active on both 4-androstene-3,17-dione and 5alpha-androstane-3alpha, 17beta-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rate were generally not affected although significant effects were noted in two cases; in one of these (17alpha-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with theanti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.
The effects of administration of testosterone propionate on the activities of seven of the enzymes of carbohydrate metabolism in normal rat mammary glands were investigated and the validity of the results was confirmed by simultaneous injection of the hormone and cyproterone acetate. The administration of the androgen increased the activities of phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and lactate dehydrogenase (LDH) in glands from both intact and from ovariectomized and adrenalectomized animals. Administration of cyproterone acetate alone resulted in a significant reduction in the activities of PFK and G6PDH and when given together with the androgen it inhibited increases in the activities of PFK, G6PDH, 6PGDH and LDH induced by testosterone. It was concluded that these results did not explain the known inhibitory effects of the androgen on normal mammary gland growth and function.
Cyproterone acetate (100 mg daily on the 5th-14th days of the normal cycle) together with ethinyl estradiol (0.05 mg daily on the 5th-25th days) was used for the treatment of hirsutism in 23 women for six months. This treatment caused a significant decrease in the severity of the hirsutism after only three months, the effect being maximal after six months. Sixty per cent of our patients reported being subjectively satisfied with the results. A relapse occurred, however, within three months of the end of the treatment in half the patients. The serum testosterone was significantly decreased after three months of treatment, but the changes in serum testosterone did not follow the changes in the clinical picture of hirsutism, suggesting that one facet in the favorable action of cyproterone acetate is an inhibition of the action of androgen on target cells. Various side effects, such as nausea, headache, loss of libido and depression, were reported very frequently, which undoubtedly limits the large scale use of this treatment, at least with the doses used in this study.
BACKGROUND: The effects of an oral contraceptive pill containing cyproterone acetate on lipid metabolism in women with polycystic ovary syndrome (PCOS) was studied. MATERIALS AND METHODS: Seventy-two women with PCOS were treated for 36 consecutive cycles with an oral contraceptive containing 0.035 mg of ethinylestradiol and 2 mg of cyproterone acetate. Hormonal, lipid and glucose profiles were studied before and after 12 and 36 cycles of treatment. Lipid, lipo-and apolipoprotein values were compared to a healthy control group. Statistical analysis was by one way analysis of variance and Bonferroni's t tests. RESULTS: The treatment suppressed gonadotropin and androgen values and increased the levels of sex hormone binding globulin. After 12 and 36 cycles a significant increase in triglycerides, high density lipoprotein (HDL) cholesterol system, and apoprotein B levels was seen. Low density lipoprotein (LDL) cholesterol and LDL cholesterol/HDL cholesterol ratio were reduced. Insulin and glucose plasma concentrations did not change. During treatment triglycerides, total cholesterol and apoprotein B values were higher than in the control group. There were no differences in plasma levels of LDL-C and HDL-C in PCOS and in the control group. CONCLUSION: Lipid and lipoprotein changes observed after treatment could be due to the estrogen dominance of the treatment. The plasma concentration of triglycerides and total cholesterol during treatment does not change appreciably and the LDL-C/HDL-C ratio improved.
Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was administered. Increasing skeletal metastases were observed in 6 patients, whereas significant reduction of metastases took place in 2 patients. Objective relief of stranguria was observed only in 3 patients. The amount of residual urine increased in 3 patients and was reduced in 5. In about one third of the patients, the prostate gland became smaller and softer. The acidic phosphatases decreased from pathological to normal values in 7 patients. There were no observed hepatic, renal or haemotological side-effects. However, serious cardio-vascular complications occurred in 6 patients, while arterial hypertension developed in 4. It is suggested that Cyproterone acetate cannot be recommended as the only kind of hormonal treatment of prostatic cancer.
Castrated adult male C57BL/6J mice displayed a wide perimedullary zone (secondary X-zone) whose cells were characterized by proliferated rough and smooth endoplasmic reticulum and elongated mitochondria with lamellar cristae. Castrated mice which received 0.08 mg/g of cyproterone acetate showed a much inhibited secondary X-zone at the light microscopic level, while at the ultrastructural level the perimedullary cells lacked the proliferated rough and smooth endoplasmic reticulum as well as the elongated mitochondria. Cyproterone acetate may inhibit the steroidogenic parameters of the androgen-producing cell population of the adrenal cortex without testicular mediation.
Adult male C57 BL/6J mice injected with 0.08 mg/g of cyproterone acetate showed an increase in cellular lipid content in the zona fasciculata and zona reticularis of the adrenal cortex. In the perimedullary region, densely staining cells aggregated to form scattered nodules. At the ultrastructural level, in the zona glomerulosa and zona fasciculata the number and size of lipid droplets increased. An apparent decrease in mitochondrial number and size and a noticeable diminution in the amount of smooth endoplasmic reticulum were also noted in the zona fasciculata. It is suggested that cyproterone acetate may have blocked steroid synthesis and increased adrenal cholesterol deposits.
Cyproterone acetate, an antiandrogen drug, is used to reduce mammalian fertility. Effects on the human testis are controversial. Findings in this study reveal that long-term treatment-7 months with 200 mg/day-leads to disappearance of the germinal cells and to Sertoli cells with either a normal or undifferentiated aspect as well as involution of the Leydig cell. Some pathogenetic hypotheses on the action of cyproterone acetate upon human spermatogenesis are discussed.
Hypophysectomized adult male C57BL/6J mice injected with 0.08 mg/g of cyproterone acetate showed large aggregates of cellular lipid as well as nodular formations in the zona fasciculata of the adrenal cortex. Daily ACTH injections (10 IU) reversed the atrophic changes noted above. At the ultrastructural level, the zona fasciculata and zona reticularis cells exhibited decreased cellular lipid content, proliferated profiles of rough endoplasmic reticulum, an increase in polyribosomes, and an active Golgi apparatus. It is believed that cyproterone acetate inhibited adrenocortical steroidogenesis by interfering with pituitary release of ACTH.
The adenohypophyses of adult male C57BL/6J mice pituitaries injected with cyproterone acetate for four weeks were examined with the electron microscope. The adrenocorticotrophs of the adenohypophysis showed an absence of the 200-nm granules that were lined along the plasma membrane, a decrease in profiles of rough endoplasmic reticulum, sparse distribution of ribosomes, and flatten Golgi membranes. It is believed the antiandrogen cyproterone acetate inhibited ACTH synthesis and release and that this was responsible for adrenocortical atrophy.
The changes resulting from treatment with cadmium were studied following the histological changes, the modification of both vascular permeability to vital dyes and of alkaline phosphatase activity in rat testis and epididymis. The testicular extravasation of acriflavine started 90 min following parenteral injection of cadmium and increased thereafter synchronous with an increase in testicular and epididymal weights due to edema. At 14 and 24 hr a striking decrease of interstitial fluorescence and tubular degeneration were noted in testis and caput epididymis due to thrombosis of the microvascular circulation. The barrier noted at 8 hr following cadmium injection. No changes of alkaline phosphatase activity was detected in testicular and epididymal blood vessels after cadmium injection. Previous treatment with cyproterone acetate accelerated the appearance of such alterations. The interstitial nuclear staining with acriflavine appeared in the testis at 1 hr and was diffuse at 90 and 120 min. cyproterone acetate seemed to accelerate the appearance of tubular degeneration at 8 hr after cadmium injection. The changes of the male rat gonad following cadmium treatment were characterized by an increased vascular permeability and generalized thrombosis. An inbalance of androgen stimulation seems to increase the blood vessels susceptibility to cadmium.
It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova, containing 0.5 mg of norgestrel, or Climen, containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption-fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios - and of bone formation-serum alkaline phosphatase and osteocalcin-were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each women) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline/creatinine ratio was insignificantly higher for the CPA-containing preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to assess the behavior of growth hormone, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) in girls with central precocious puberty treated with gonadotropin-releasing hormone (GnRH) analog-therapy, we studied 14 girls with this condition, the patients were subdivided into two groups, according to the therapy followed. Group A (n = 7; age 4.2-7.1 years) received GnRH analog in combination with cyproterone acetate, and Group B (n = 7; age 4.4-6.9 years) received long-acting analog alone. Before treatment, IGF-I levels were significantly increased compared to healthy age-matched children in the two groups (447 +/- 33 micrograms/l for Group A and 435 +/- 38 micrograms/l for Group B vs. control 175 +/- 78 micrograms/l; p < 0.01). Moreover, serum IGFBP-3 levels were significantly higher than the age-related reference range for IGFBP-3 (4478.2 +/- 178 micrograms/l for Group A and 4532.3 +/- 167 micrograms/l for Group B vs. control 2905 +/- 641 micrograms/l; p < 0.01). During the two years of gonadal suppression, Group A patients showed a significant decrease in IGF-I and IGFBP-3 levels, while in Group B there was no significant change in IGF-I; moreover, in Group B, IGFBP-3 levels increased significantly compared to baseline values during the first year of treatment (4532.3 +/- 167 micrograms/l vs. 5410.3 +/- 169 micrograms/l; p < 0.05) and decreased significantly at the end of the second year of treatment (3816.1 +/- 189 micrograms/l vs. 5410.3 +/- 169 micrograms/l; p < 0.01). Our study shows that the two different treatments of precocious puberty (with and without cyproterone acetate) have different effects on IGF-I and IGFBP-3, and suggests that these growth factors are under different metabolic regulation.
It has been suggested that cyproterone acetate (CPA) has a mutagenic potency. It has been postulated that a threshold dosage of CPA has mutagenic effects, but in the same way data have been published documenting that a continuous low dosage of cyproterone acetate leads to a reduction of mutagenic episodes. Despite published data about higher levels of DNA adduct creations due to CPA an international multicentre study analysing 2,506 patients with 7,971 patient-years that used CPA could not find any liver cell cancers, even if due to epidemiological data 6 liver cell cancers should have occurred upon this study group. The present study deals with the evaluation of 57 women which received CPA in combination with EE2 11-13 years before. The daily dosage was 2 mg CPA in combination with 35 mg or 50 mg EE2. In Germany these drugs were registered under the name of Diane 35 or Diane 50. Long-term follow-up evaluation concerning side effects, especially the appearance of liver cell carcinomas, were the aim of this study. With the records of 32% (18/57) of the above mentioned patient group the following long-term follow-up side effects could be observed: 1) weight gain, 2) headache, 3) migraine, 4) gastrointestinal disorders, 5) mood affections/depressions, 6) oedema of the legs, 7) skin affections, 8) mastodynia. No benign liver tumor or liver cell carcinoma was detected upon our group of investigated patients. In conclusion we can affirm that the use of CPA in a dosage of 2 mg per day does not lead to serious side effects under long-term follow-up observation conditions and that it's use does not correlate with a higher appearance of liver cell carcinomas.
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.
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.