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PubMed1985

Spontaneous gonadotrophin pulsatility and ovarian morphology in girls with central precocious puberty treated with cyproterone acetate.

We have studied four girls with central precocious puberty treated with cyproterone acetate for a mean of 3.6 years (range 1.5-6.3 years). Pelvic ultrasound assessment demonstrated suppression of the ovarian morphology of central precocious puberty despite the presence of spontaneous pulsatile gonadotrophin secretion at night. We suggest that the previously reported effects on gonadotrophin secretion induced by cyproterone acetate therapy, administered in recommended doses, are minor and that the predominant effect of cyproterone acetate in the treatment of girls with central precocious puberty is direct inhibition of ovarian steroidogenesis.

Child↗
PubMed1986

Paradoxical effects of the anti-androgen cyproterone acetate on lipid and lipoprotein metabolism.

The effects on fasting serum lipids of the potent anti-androgen, cyproterone acetate (CA) and the oestrogen, ethinyl oestradiol (EO) given both alone and in combination were examined in women acting as their own controls. Cyproterone acetate alone caused significant reductions in total cholesterol, high density lipoprotein subfraction 2 cholesterol (HDL2) and low density lipoprotein cholesterol (LDL). Ethinyl oestradiol alone significantly increased triglycerides, HDL and HDL2 and reduced LDL, and there was also a significant increase in the HDL/LDL and HDL2/LDL ratios. The two steroids were administered in combination according to a reverse sequential regime. The 28-day treatment cycle thus included Phase A during which both drugs were given followed by Phase B when EO alone was given. Triglycerides rose significantly in Phases A and B to the same extent as for the group taking EO alone. High density lipoprotein cholesterol was unchanged but HDL2 was reduced in both phases and this effect could not be overcome by increasing the dose of oestrogen. Low density lipoprotein cholesterol fell and the HDL/LDL ratio rose during the two Phases and these changes were significant during Phase A. The effects of EO demonstrated in this study are consistent with previous reports. Cyproterone acetate, however, has properties conventionally ascribed to both synthetic androgens (e.g. lowering of HDL2) and oestrogens (e.g. lowering of LDL). The limitations of the terms androgenic and oestrogenic activity in relation to their conventional associations with changes in lipid and lipoprotein levels are discussed.

Acne Vulgaris↗
PubMed1985

Further regression of seminal vesicles of castrated guinea pig by administration of cyproterone acetate.

It has been established that a low level of secretory activity persisted in seminal vesicles of guinea pigs long after castration and that this may be due to a higher extratesticular androgen level in this animal. A RIA study revealed that the normal serum testosterone concentration of the guinea pigs was comparable to that of the rats, but the basal serum testosterone level after castration was ten times higher than rats under a similar condition. It was also shown that cyproterone acetate did not significantly lower the basal serum testosterone concentration in the castrated guinea pigs. The higher basal serum testosterone level is believed to be responsible for the slow and incomplete regression of this gland in the guinea pigs. There was a significant reduction in wet weight of the seminal vesicles after the treatment of castrated guinea pigs with cyproterone acetate. Ultrastructural study showed that there were both qualitative and quantitative changes in the cytoplasmic organelles. The Golgi apparatus further reduced in size and in the number of associated vesicles and vacuoles. There was a marked decrease in the number and size of secretory granules and lysosomes and an increase in the degree of undulation of the basement membrane. Accumulation of lipid droplets and glycogen was commonly observed. All these morphological evidences showed that further regression of the castrated guinea pig seminal vesicles can be achieved by cyproterone acetate treatment.

Animals↗
PubMed1982

Impaired pregnenolone secretion after combined cyproterone acetate and ethynyl estradiol therapy in hirsute patients.

6 women affected by hirsutism, either of idiopathic origin or due to polycystic ovary syndrome, have been treated with cyproterone acetate and ethynyl estradiol in combined therapy using, respectively, 100 mg and 50 micrograms/day, from the 5th to the 25th day of the cycle. The adrenal function was assessed before treatment and at the end of the 4th month of therapy, evaluating the peripheral plasma concentrations of pregnenolone (delta 5P), progesterone, 17-OH-progesterone, dehydro-epiandrosterone sulfate, androstenedione, testosterone, and cortisol in basal conditions and after dexamethasone suppression and an adrenocorticotropic hormone (ACTH) stimulation test. A group of healthy, untreated females were examined in the early follicular phase, as controls, Before therapy, the hirsute patient showed testosterone and androstenedione plasma levels, which were significantly higher than in the controls, and a significant reduction in pregnenolone response to ACTH. After 4 months of therapy with cyproterone acetate plus ethynyl estradiol, a significant decrease was found in testosterone and androstenedione plasma levels, and pregnenolone basal plasma levels, dexamethasone suppressibility, and response to ACTH were also markedly reduced, showing a significant difference versus the same patients before therapy and versus the control group. The existence of an impairment in adrenal function after cyproterone acetate plus ethynyl estradiol therapy at the given dose seems to be evident only in the case of directly ACTH-dependent adrenal enzymatic activities responsible for cholesterol cleavage to pregnenolone.

17-alpha-Hydroxyprogesterone↗
PubMed1981

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

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

Aged↗
PubMed1988

Effect of cyproterone acetate on the pregnancy-blocking ability of male mice and the possible chemical nature of the pheromone.

Even though castration abolished the ability of alien males to induce implantation failure (the Bruce effect) in newly inseminated females, treatment of intact alien males with the steroidal antiandrogen, cyproterone acetate, for 14 days (short term) did not significantly depress their ability to induce the Bruce effect. However, prolonged treatment (42 days) with cyproterone acetate suppressed the pregnancy-blocking ability of alien males to some extent, possibly due to the antigonadotrophic properties of the drug. Ovariectomized alien females treated with implants of testosterone (androgenized females) exhibited the ability to block implantation in newly inseminated females, but concurrent treatment of androgenized females with cyproterone acetate did not depress this ability. The results strongly suggest that the pheromone involved in the male-induced implantation failure is not the product of an androgen-dependent tissue, but is likely to be a product of androgen metabolism.

Animals↗
PubMed1984

Sexual maturation in male mice treated with cyproterone acetate from birth to puberty.

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.

Aging↗
PubMed1982

Effect of LHRH on cyproterone-acetate-injected adenohypophyses of castrated mice.

Luteinizing hormone releasing hormone (LHRH)-treated adenohypophyses from castrated, cyproterone acetate-injected adult male mice were studied with transmission electron microscopy (TEM). LHRH-treated luteinizing hormone (LH) gonadotrophs (types a and b) in castrated mice showed accumulation of secretory granules at the capillary pole, dilated Golgi apparatus and extensive rough endoplasmic reticulum (RER) profiles. Following treatment, granular content in LH type-a gonadotrophs was decreased and profiles of secretory granules were seen in the intercellular and perivascular spaces. Some RER cisternal hypertrophy was noted, and the Golgi apparatus was dilated. In LH type-b gonadotrophs there were secretory granules lined along the plasma membranes, several lysosomes, multivesicular bodies, and short RER profiles. LHRH stimulated secretory granules release of LH gonadotrophs in cyproterone-acetate-treated castrated mice. Cyproterone acetate may have blocked hypothalamic LHRH stimulation of pituitary LH gonadotrophs.

Animals↗
PubMed1991

The polycystic ovary syndrome presenting as resistant acne successfully treated with cyproterone acetate.

OBJECTIVE: To review a group of Australian women presenting to a reproductive endocrinologist with acne and investigate how many had androgen excess and how they had responded to endocrinological therapy. DESIGN: All patients referred to me over a 12 month period were included in the study and investigated in a standard manner. Medical therapy was given in a non-randomised manner based on clinical and biochemical evidence. SETTING: Most patients were referred to my private practice, but all public patients seen over this period were also included. PATIENTS: Subjects were women who presented with acne. Some were also hirsute and/or had menstrual irregularities. The total group consisted of 157 subjects. Patients with thyroid disease, hyperprolactinaemia, and late-onset congenital adrenal hyperplasia, and menopausal women were excluded, and the final study group consisted of 90 subjects. INTERVENTIONS: Women presenting with acne but no hirsutism and an elevated level of dehydroepiandrosterone sulphate were treated with low-dose dexamethasone. All other subjects were treated with ethinyloestradiol and cyproterone acetate. MAIN OUTCOME MEASURES: (i) The diagnosis of polycystic ovary syndrome and (ii) the effect of endocrinological therapy on their acne. RESULTS: Of the 90 subjects presenting with acne, 67 (74%) were found to have the polycystic ovary syndrome. In all cases the acne was substantially reduced by treatment. All 30 subjects who had previously failed to respond to standard dermatological preparations were successfully treated with combined ethinyloestradiol and cyproterone acetate therapy. CONCLUSIONS: The polycystic ovary syndrome is commonly found amongst women complaining of acne. Some patients will not have excess body hair, obesity or menstrual irregularities. Among women with resistant acne, not responding to conventional treatments, the polycystic ovary syndrome is very common. Treatment with ethinyloestradiol and cyproterone acetate is an extremely effective, safe and well tolerated therapy for these women.

Acne Vulgaris↗
PubMed1989

[Cyproterone acetate in the treatment of post-orchiectomy flushing].

Out of 17 patients who had been submitted to subcapsular orchidectomy as the primary treatment of cancer of the prostate, postorchiectomy flushing was found in eight, corresponding to 47%. Six of the patients were treated with cyproterone acetate in a dosage of 50-100 mg daily. In all of these clinically significant reduction in the frequency and duration of the flushing was found. In four out of five patients with possible recurrent flushing after withdrawal of cyproterone acetate, recommencement of the treatment proved necessary. Administration of cyproterone acetate appears to be equally effective in a dosage of 100 mg daily as in a dosage of 300 mg daily and this reduces the side effects and expenses considerably. If it is possible to obtain a more extensive patient material without hormone treatment, a placebo-controlled investigation with the reduced dosage is desirable.

Aged↗
PubMed1989

The effect of cyproterone acetate on hair roots and hair shaft diameter in androgenetic alopecia in females.

Twenty female patients suffering from androgenetic alopecia were treated during one year with 50 micrograms ethinyloestradiol plus 2 mg cyproterone acetate and additional 20 mg cyproterone acetate on days 5-20 of the menstrual cycle. The control group consisted of eight untreated female patients with androgenetic alopecia. The parameters used to evaluate therapeutic results were trichogram, hair shaft diameter of full anagen and number of hairs measuring less than 40 microns. Hair roots were epilated from two locations of the scalp: fronto-cranial and left temporal (reference point). The trichogram of the fronto-cranial scalp region showed an increase of anagens as well as a decrease of telogens. These changes were statistically highly significant. Further, there was a decrease of dysplastic/dystrophic forms. The left temporal scalp region showed no significant differences. The mean hair shaft diameter of full anagen (n = 8) increased, while the number of hairs measuring less than 40 microns (n = 8) decreased. The last two findings showed no statistically significant differences. The therapeutic results warrant the conclusion that cyproterone acetate seems to be effective in androgenetic alopecia in women.

Adolescent↗
PubMed1981

Oestrogenic activity of cyproterone acetate in female mice.

Effects of cyproterone acetate, a synthetic steroidal compound, on the reproductive organs of female mice 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 animals taking uterine weight, vaginal keratinization and other biochemical oestrogen sensitive 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 effects of oestradiol dipropionate in ovariectomized animals, thus indicating oestrogenic activity of the compound.

Animals↗
PubMed1984

Treatment of severe hirsutism resulting from hyperandrogenism with the reverse sequential cyproterone acetate regimen.

Women with severe hirsutism resulting from hyperandrogenism often respond poorly to suppressive therapy aimed at decreasing adrenal or ovarian androgen production. Antiandrogens, such as cyproterone acetate, prevent androgens from expressing their activity at target sites by inhibiting the formation of the androgen/cytosol binding protein complex. Seven severely hirsute hyperandrogenic women were treated for six months with the reverse sequential cyproterone acetate regimen. Pretreatment plasma testosterone (T) levels were elevated in all subjects, and sex hormone binding globulin (SHBG) binding capacity was depressed. A free testosterone index, as assessed by the T/SHBG ratio, was markedly elevated. A marked and significant decrease in T levels and the T/SHBG ratio occurred during the first two cycles of treatment (p less than 0.01). Hirsutism grading assessed by the semiquantitative method of Ferriman and Gallwey did not change significantly until four months after the beginning of therapy but improved by six months of treatment. There was a marked antigonadotropic effect in terms of suppression of LH and FSH. The reverse sequential cyproterone acetate regimen produces rapid normalization of the plasma T, SHBG and free testosterone index, but resolution of the hirsutism is slower and requires several months of therapy.

Adult↗
PubMed1981

[Long-term treatment of virilized women with cyproterone acetate (author's transl)].

76 women with virilizing features (68 women suffering from hirsutism and 8 from acne) were treated on average for 25 months according to different models of Androcur medication. Success of treatment was clinically assessed as good in 3/4 of the cases and slight in the remaining 1/4. However, treatment is more successful in cases of adrenal hirsutism than in idiopathic hirsutism. Moreover, success of treatment seems to be better in women below 35 than over 35 years of age. Side effects, mostly bleeding anomalies and fatigue, were found in 31 women; these must be attributed to the gestagenic component of cyproterone acetate. By contrast, 12 women showed positive side effects such as weight reduction, improvement in depression states and reversal of hair loss, which must be attributed to the antiandrogenic component. The selected continuation rate in all subjects was 86% and the unselected 72%, over a treatment period of 4.5 years. Furthermore, hormonal controls were carried out under treatment. These showed, on average, a depression of plasma androstendione of 17%, of total plasma testosterone of 47%, as well as an inhibition of the testosterone/sex hormone-binding globulin quotient of 58%. These inhibition effects speak in favour of alterations taking place in steroid metabolism. However, by inhibition of androgenic serum levels, the mechanism of cyproterone acetate is only assisted, while the main mechanism is based on peripheral receptor inhibition. Furthermore, as additional component in this action a slight increase in plasma binding capacity was found during combined cyproterone-oestrogen treatment.

Acne Vulgaris↗
PubMed2005

Rheology and NMR self-diffusion experiments as well as skin permeation of diclofenac-sodium and cyproterone acetate of new gel preparations.

The viscoelastic properties of two transparent semisolid preparations, one consisting of surfactant, paraffin oil, and water (BAS), and the other consisting of surfactant, cetylstearyl-2-ethylhexanoate, and water (CUBO), were characterized by oscillatory measurements. In (1)H-NMR diffusion experiments it was confirmed that the formulations are O/W systems, and the three-dimensional packing of the closed globular aggregates form a cubic structure. Moreover, standard diffusion experiments with porcine skin using Franz cells were performed with incorporated diclofenac-sodium and cyproterone acetate, respectively. The cumulative amount released after 48 h of diclofenac-sodium were excellent with 665.28 microg/cm(2) and with 36.7 microg/cm(2) for cyproterone acetate. The new drug-containing formulations were also prepared as transdermal patches by using carrageenan as a matrix. In diffusion studies zero-order kinetics was found for both drugs, but with a higher lag time for cyproterone acetate. The total work of adhesion was analyzed by tensile studies on porcine skin and found to be very good. The presented cubic gels as well as mixtures with carrageenan are promising alternative drug carrier systems for topical pharmaceutical as well as cosmetics.

Animals↗
PubMed1975

Effects of cyproterone acetate on uterine motility in rats.

The effect of cyproterone acetate, an antiandrogen, on uterine contractility when the compound is administered to rats during midpregnancy was investigated. Pregnant Wistar rats were given cyproterone acetate subcutaneously on Days 8-11 of gestation. The results indicate that cyproterone acetate, either directly or indirectly, inhibits uterine contractility, an effect that may explain the prolongation of the gestational period observed in all treated animals.

Animals↗
PubMed1995

Nuclear matrix condensation and c-myc and c-fos expression are specifically altered in culture rat hepatocytes after exposure to cyproterone acetate and phenobarbital.

Regenerative or hyperplastic growth promotes carcinogenesis and can be induced by many nongenotoxic carcinogens. The mitogenic potential of the rodent liver tumor promoters, cyproterone acetate and phenobarbital was investigated in primary rat hepatocyte cultures. Two premitotic markers were analyzed, the expression of two immediate-early genes (c-fos and c-myc) and the decrease in the nuclear quinacrine dihydrochloride fluorescence indicative for a G0-G1 cell cycle shift. C-fos expression and decrease in nuclear fluorescence could be induced by both chemicals, phenobarbital being the lesser potent, whereas c-myc expression was only inducible by cyproterone acetate. In situ hybridization with c-myc revealed that both chemicals enhanced c-myc mRNA levels in individual cells, however the number of responding hepatocytes was increased by cyproterone acetate only. The chemical-induced premitotic changes in hepatocytes were highly specific in terms of affected genes and ploidy levels of responding hepatocytes.

Animals↗
PubMed1977

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

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

Animals↗