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The effects of cyproterone acetate on sleeping and waking penile erections in pedophiles: possible implications for treatment.

This study reports the short term effects in five pedophiles of the antiandrogenic drug cyproterone acetate (CPA) on nocturnal penile tumescence (NPT); penile responses to erotic stimuli in the laboratory; and sex hormones (testosterone, LH, FSH and prolactin). During the administration of CPA, NPT, laboratory arousal and hormone measures (except prolactin) all decreased. Waking laboratory measures were influenced less and were more variable (one subject showed greater arousal) than NPT measures. The changes in NPT closely paralleled the reduction in testosterone. The results are discussed with reference to the known psycho-neuroendocrinology of sleeping and waking erections.

Cyproterone↗

Treatment of hirsutism by oral cyproterone acetate and percutaneous estradiol.

Twenty hirsute women were treated with 50 mg cyproterone acetate orally, administered from the 5th to the 25th day of the menstrual cycle, along with 3 mg 17 beta-estradiol administered percutaneously from days 16-25. Percutaneously administered 17 beta-estradiol was used rather than ethinylestradiol in order to avoid the side effects of oral administration of synthetic estrogens. From a clinical point of view there was a dramatic improvement of hirsutism after 3-6 months of treatment. Biologically, plasma testosterone decreased markedly (P < 0.01) from 64.6 +/- 24.2 ng/dl (n = 20) to 25.2 +/- 11.8 (n = 20), 26.1 +/- 16.6 (n = 16), and 13.3 +/- 10.8 ng/dl (n = 14) after 3, 6, and 9 months of treatment. There was also a significant decrease in delta 4-androstenedione from 251.0 +/- 110.2 ng/dl to 129.9 +/- 66.5, 114.2 +/- 45.8, and 62.0 +/- 21.5 ng/dl after the same periods. From these results it may be assumed that this therapeutic combination has an antigonadotropic effect, as confirmed by the decrease in plasma estradiol, FSH, and LH and the absence of a significant progesterone level in all cases. Plasma and urinary cortisol, lipids, and hepatic tests remained normal. The good clinical and biological tolerance of this treatment makes it interesting to consider for use in the management of hirsutism.

Androstenedione↗

Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men.

To test the effects of antiandrogen treatment on the endocrine system 20 normal young men were treated with 750 mg/day flutamide [4-nitro 3'-trifluoromethylisobutyranilide (FLU)] or 100 mg/day cyproterone acetate (CPA) for 14 days followed or preceded by a placebo treatment of the same duration 4 weeks apart. Allocation of both drugs and sequence of active and placebo substance was by random number in a double blind design. On days 1 and 14 two basal blood samples were obtained 15 min apart followed by an iv injection of 25 micrograms GnRH and 10 mg metoclopramide (MTCL). Subsequently blood samples were taken after 25, 45, 60, and 90 min. On day 8 the GnRH/MTCL test was performed after 13 basal blood samples were obtained to establish a baseline for PRL concentrations unbiased by short term stress. After 14 days of FLU treatment, serum testosterone (T) increased significantly [17.4 +/- 1.4 (SE) vs. 26.9 +/- 1.5 nmol/liter, as well as estradiol (E2) concentrations (144 +/- 12 vs. 177 +/- 20 pmol/liter). Dihydrotestosterone increased slightly after 14 days of FLU administration (1.59 +/- 0.14 vs. 1.98 +/- 0.30 nmol/liter). At the same time basal LH concentrations were significantly elevated (5.9 +/- 0.5 vs. 8.6 +/- 0.6 ng/ml), whereas FSH levels were not affected (2.8 +/- 0.6 vs. 2.8 +/- 0.6 ng/ml). No changes in PRL values were detected throughout treatment with FLU. The effect of CPA was quite different. At the end of the treatment phase, serum T levels were reduced considerably (14.6 +/- 1.8 vs. 3.3 +/- 0.4 nmol/liter). Serum E2 decreased similarly (95 +/- 13 vs. 35 +/- 6 pmol/liter). Conversion of T to dihydrotestosterone was also diminished significantly (1.72 +/- 0.33 vs. 1.14 +/- 0.33 nmol/liter). Both gonadotropins were significantly depressed after 14 days of CPA administration (LH, 5.6 +/- 0.7 vs. 2.8 +/- 0.4 ng/ml; FSH, 2.4 +/- 0.3 vs. 1.4 +/- 0.2 ng/ml). Basal PRL levels were not affected, although the response of MTCL was reduced at the end of the treatment phase. Both drugs reduced the response of LH and FSH to GnRH administration.

Adult↗

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

A randomized cross-over study was done to compare the therapeutic efficacy of cyproterone acetate (CPA) and a depot preparation of the LHRH superagonist (DTrp6-LHRH) in 10 patients with polycystic ovarian disease (PCO). All patients were treated with both agents (50 mg/day CPA, orally and (3 mg DTrp6-LHRH, im, approximately once a month) for 3 months, the 2 treatment periods being separated by 6 months. Both treatments resulted in marked clinical improvement, with diminished acne and seborrhoea and normalization of ovarian size by ultrasonographic criteria. In response to CPA treatment, basal plasma gonadotropin levels decreased, but the response to a LHRH test was not completely suppressed. Plasma estradiol, estrone, testosterone, and androstenedione levels significantly decreased, but urinary 3 alpha-androstanediol and plasma dehydroepiandrosterone sulfate levels did not change significantly. In contrast to CPA treatment, both basal and stimulated gonadotropin levels were completely suppressed after 3 weeks of treatment with DTrp6-LHRH. After a slight initial evaluation on day 2, plasma estrogen and androgen levels, with the exception of dehydroepiandrosterone sulfate fell into the castrate range urinary 3 alpha-androstanediol excretion decreased significantly. Thus, in patients with PCO, LHRH-A induced more complete gonadotropin inhibition than did CPA. After cessation of either therapy, the disease rapidly recurred.

Adult↗

Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia.

Thirty late-onset adrenal hyperplasia patients consulting for isolated hirsutism were randomly divided into two groups; group 1 (n = 16) was treated with hydrocortisone in order to suppress androgen adrenal secretion, and group 2 (n = 14) received cyproterone acetate (CPA) antiandrogen therapy to inhibit peripheral androgen activity. The clinical and hormonal effects of each type of treatment were evaluated. Before treatment, the clinical and hormonal profiles of the two patient groups did not differ significantly. Excellent clinical evolution in terms of the regression of hirsutism was observed in the CPA-treated patients (54% decrease in the clinical score in 1 yr), in contrast with the slight decrease in hirsutism (26%) after hydrocortisone treatment. In hydrocortisone-treated patients, plasma androgen decreased to normal levels: testosterone from 3.05 +/- 1.45 to 1.46 +/- 0.42 nmol/L and delta 4-androstenedione from 13.6 +/- 4.1 to 6.33 +/- 1.47 nmol/L. Conversely, in CPA-treated patients, only a slight decrease in testosterone from 2.98 +/- 1.98 to 2.29 +/- 0.64 nmol/L and in delta 4-androstenedione from 12.9 +/- 5.9 to 9.86 +/- 2.23 nmol/L was observed. This slight decrease in plasma androgens contrasts with the rapid clinical improvement after CPA. These results emphasize the importance of peripheral receptivity to androgens in the clinical expression of hyperandrogenism. Moreover, they indicate that peripheral antiandrogen therapy may be more appropriate in late-onset adrenal hyperplasia patients than conventional adrenal inhibition using cortisone therapy.

Adolescent↗

Comparison of sequential cyproterone acetate/estrogen versus spironolactone/oral contraceptive in the treatment of hirsutism.

The effects of the antiandrogen drugs cyproterone acetate (CPA) and spironolactone on hair growth and androgen levels were compared in a randomized study of 48 hirsute women. Twenty six subjects completed 6 months of therapy with 100 mg/day CPA and 19 subjects completed 6 months of 100 mg/day spironolactone. All except 10 subjects received concomitant estrogen therapy. Measured objectively, total hair diameter fell by 17.1% with spironolactone (P less than 0.001), and by 16.8% with CPA (P less than 0.001). The diameter of the hair medulla fell by 17.8% with spironolactone (P less than 0.01), and by 31.7% with CPA (P less than 0.001). There was no difference between the drugs in their effect on hair diameter. Plasma testosterone levels also fell significantly with both drugs. As a subjective assessment of treatment efficacy, the frequency with which subjects performed cosmetic measures was recorded. This fell by 38% with spironolactone and by 44.7% with CPA (P less than 0.001 both drugs), and again there was no difference between the drugs. Side effects caused cessation of treatment in one subject taking CPA and two subjects taking spironolactone, and milder side effects were noted in two further subjects from each treatment group. We conclude that spironolactone and CPA, in the dosages used in this study, are effective and well tolerated agents for the treatment of hirsutism, and that neither drug demonstrates a particular advantage over the other.

Adult↗

[Effect of cyproterone acetate on aromatase activity in cultured human genital skin fibroblasts: intracellular control of aromatase activity].

Cyproterone acetate(CA), a well-known competitive antiandrogen, has been used for the treatment of precocious puberty, prostatic adenocarcinoma, hirsutism and hypersexuality. However, there have been some reports of troublesome gynecomastia developing during the use of this drug. It was, therefore, of interest to investigate the effect of CA on peripheral aromatization, since it is the major source of circulating estrogens in men. Our recent studies of aromatase activity in human skin fibroblasts demonstrated that the skin is an important site of extraglandular aromatase activity in men and suggested that these cells might provide a valuable new system in which to study the enzyme. Estrogen formation was assayed by the [3H]H2O technique, after 3h incubation of the cells with androstenedione. The initial experiment was designed to test the effect of CA (10(-8) to 10(-5) M) on baseline aromatase activity during a 12h preincubation in the presence of fetal bovine serum (FBS). Baseline aromatase activity was not affected by the presence of CA, whereas medroxyprogesterone acetate, a similar synthetic progestogen, induced a 2-fold stimulation of aromatase activity at a concentration of 10(-5) M. In cells preincubated with dexamethasone (DEX) in the presence of FBS, aromatase activity was stimulated markedly. When the cells were preincubated in the medium containing FBS with DEX (2.5 X 10(-7) M) in the presence of CA (10(-7) to 10(-4) M), DEX-stimulated levels of aromatase activity were inhibited by CA in a dose-dependent fashion. A competitive binding assay using [3H]DEX, showed that CA was able to compete with DEX for glucocorticoid receptor and the relative binding affinity of CA was approximately 50 times less than DEX. This suggested that the inhibitory effect of CA was due to competition with DEX for receptor binding. Aromatase activity was also stimulated by (Bu)2cAMP (1mM) in the absence of FBS. The stimulatory effect of (Bu)2 cAMP was maximal after 12-24h of preincubation, and this level was maintained for 60h. Similar to the DEX stimulation, stimulation of aromatase activity by (Bu)2cAMP required both RNA and protein synthesis, since the stimulatory effect of (Bu)2cAMP was abolished by co-preincubation with cycloheximide or actinomycin D. When CA was present during either the 12h preincubation or assay incubation, no difference was found in the (Bu)2cAMP-stimulated levels of aromatase activity. On the other hand, the non-aromatizable androgen dihydrotestosterone (DHT) (10(-8) to 10(-6) M) inhibited the stimulation of aromatase activity by (Bu)2cAMP in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗

The effect of cyproterone acetate on pituitary-ovarian function and clinical symptoms in hirsute women.

Ten hirsute women in fertile age were given 50 mg cyproterone acetate (CA) on day 5--14 and 50 micrograms ethinyl oestradiol (EE2) on day 5--21 except during the first treatment cycle when EE2 was given on day 15--21. The treatment lasted for 12 months. Clinical examination and hormone analysis were undertaken every third month. LRH tests were performed prior to treatment with CA in late follicular phase and after one week of administration of the drug. Subjective improvement of hypertrichosis was reported in 7 women, objectively a significant decrease in hair scores was observed. Short-term effects of CA alone included significantly decreased serum levels of oestrogens while FSH, LH, 4-androstene-3,17-dione and testosterone remained unaffected. Long-term administration of CA and EE2 resulted in significantly decreased serum levels of FSH, LH and oestrogens whereas 4-androstene-3,17-dione and testosterone were not affected. The gonadotrophin response to LRH did not reveal any significant difference before and after treatment. 4-Androstene-3,17-dione and testosterone did not change during the LRH tests but increased levels of oestrogens were observed at the end of the test during the CA treatment. Since CA alone causes decreased oestrogen levels without any suppression of the basal gonadorrohin levels, it is speculated that CA directly affects the ovarian steroid biosynthesis. On the other hand the adrenal androgens seem to be unaffected by the drug.

Adrenal Glands↗

Microautoradiographic studies on distribution of 5 alpha-dihydrotestosterone, cyproterone acetate and oestradiol-17 beta in human prostatic hyperplasia tissue transplanted to juvenile rats.

While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to new born rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radio-active androgen 5 alpha-dihydrotestosterone (5 alpha-DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17 beta (E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3: 1 and 1.5: 1 for epithelium to stroma after administration of [3H] 5 alpha-DHT and [3H]CA administration respectively and 0.5: 1 after [3H]E2. The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5 alpha-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [3H] 5 alpha-DHT and [3H]CA administration both in the epithelium and stroma suggest that an antagonism may also exist in the stroma.

Aged↗

Foetal exposure to low doses of cyproterone acetate in the rat leads to functional endocrine abnormalities despite normal sexual morphogenesis.

Cyproterone acetate (CPA), an anti-androgen and a gestagen, was administered to pregnant Wistar rats at very low doses (0.5 or 1.0 mg/day) between days 15 and 20 of pregnancy. No anatomical abnormalities were observed in external genitalia of their offspring, either immediately after birth or upon reaching maturity. However, when these animals were studied in adulthood, several endocrine abnormalities became apparent. While the pituitary content of Prl decreased in the CPA-exposed offspring, the amount of LH increased. Plasma Prl was lower and FSH was higher in treated females whereas plasma LH was higher in both sexes compared to controls. Treatment induced a Prl-responsiveness to TRH in both sexes and an enhanced LH- and FSH-response to GnRH in females. Testicular weights, LH/hCG receptors in testicular membrane preparations and testosterone response to in vivo hCG stimulation were identical in both the treated and control groups. Basal testosterone, however, was increased in the face of decreased ventral prostate weight and of decreased androgen receptors in prostate cytosol, indicating androgen resistance of the target organ. Females displayed normal oestrous cycles, but possessed enlarged ovaries and uteri. The decrease in oestrogen receptors (ER) in uterine cytosol during oestrus and the relative increase of ER in dioestrus were consistent with enhanced oestrogenic action, presumably by increased oestrogen secretion by the hyperstimulated ovaries.

Animals↗

Cyproterone acetate as initial treatment and maintenance therapy for hirsutism.

Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5-15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 micrograms ethinyloestradiol (Diane) given on days 5-25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane plus 25 mg CA with Diane plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane and 48% on placebo and Diane (P less than 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interactions of an anti-androgen (cyproterone acetate) with the androgen receptor system and its biological action in the rat ventral prostate.

Male Wistar rats were castrated and implantated with testosterone-filled silastic depots (in vitro release rate: 60 micrograms/24 h) prior to treatment with 10 mg cyproterone acetate (CyAc) on day 1, and 5 mg on days 4, 7, 10 and 13. Animals were sacrificed on day 14. Control animals were treated identically, with the exception of CyAc administration. Blood was collected and the ventral prostates of 6-8 animals were pooled, homogenized and processed into cytosol and purified nuclei. Steroid determinations (CyAc, testosterone, 5 alpha-dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol)) were performed by RIA. Specifically bound DHT (charcoal resistant DHT = CR-DHT) represents DHT values (RIA) following treatment of cytosol or nuclear extract with dextran coated charcoal. The androgen receptor was determined in cytosol and nuclear extract by 'exchange assay' using [3H]methyltrienolone (MT) (18 h, 15 degrees C). The main results were: 1) The steroid levels in plasma (testosterone, DHT, 3 alpha-diol) were in the range of untreated adult animals and not significantly influenced by the CyAc treatment. Final CyAc levels were 305 +/- 58 nmol/l (mean +/- SD, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗

Time dependency and reversibility of the effects of exclusive cyproterone acetate therapy on pituitary adrenal function in hirsute women.

The effects of cyproterone acetate (CA) administration on the pituitary-adrenal axis were studied in 30 hirsute females. The patients were treated continuously with a daily dose of 100 mg of CA for a maximal period of 12 months. Insulin-induced hypoglycaemia and ACTH infusion were performed on pre-treatment conditions and after 1, 4, 6 and 12 months of CA treatment. From a clinical point of view, a dramatic improvement of hirsutism was evident after 6 months of therapy. The most commonly reported side effects were amenorrhoea and transient uterine haemorrhage. Apart from asthenia, no symptoms of adrenal insufficiency were noticed. No changes in pituitary-adrenal secretion were observed during the first 4 months of therapy. From the 6th month, a reduction in basal as well as stimulated cortisol levels was seen. Simultaneously, an enhanced ACTH response to hypoglycaemia was observed. Both effects became more pronounced after 1 year of treatment. There were no significant changes in ACTH basal values. Six months after discontinuation of the drug, adrenocortical reserve improved but was still slightly reduced when compared to pre-treatment range at that time. These findings suggest a time-dependent negative effect of CA on adrenal steroidogenesis which shows a reversible character 6 months after antiandrogen withdrawal. Therefore, steroid cover should be considered for intercurrent illness in patients treated for longer than 6 months with this therapeutic regime.

Adrenocorticotropic Hormone↗

Effect of oestrogen or cyproterone acetate treatment on adrenocortical function in prostate carcinoma patients.

The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydro-epiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (-40%), DS (-73%) and T (-58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (-89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.

Adrenal Cortex↗

Hair growth and androgen responses in hirsute women treated with continuous cyproterone acetate and cyclical ethinyl oestradiol.

Eighteen hirsute women (8 with polycystic ovarian syndrome, 10 with idiopathic hirsutism) were treated for up to 12 months with cyproterone acetate, 150 mg daily, and ethinyl oestradiol, 50 micrograms on days 5-25 of the menstrual cycle. Hair growth rate and density were measured from standardized serial photographs of a shaved skin area. A significant reduction was seen in mean hair growth rate, total plasma testosterone, free testosterone index, plasma dehydroepiandrosterone, and plasma androstenedione. LH and FSH also fell and sex hormone binding globulin level increased. No significant changes occurred in hair density or in serum PRL levels. A significant correlation was observed between hair growth rate and total plasma testosterone for the pooled results (r = 0.35, P less than 0.005). No significant correlations were seen between hair density and the endocrine parameters studied.

Adult↗

The treatment of essential hirsutism in women with cyproterone acetate and ethinyl estradiol. Clinical and endocrine effects in 10 cases.

Ten women with essential hirsutism were treated for one year with cyclic administration of cyproterone acetate and ethinyl estradiol. Biochemical and clinical control took place after 1, 3, 6 and 12 months of treatment. In 4 patients great improvement of hirsutism was noted, but only after 6 months of therapy. In 4 patients there was some improvement, while 2 were resistant. Side effects included reduced libido in 4 cases, mental depression in 3, dry skin and itching in 4 and transient nausea in one, but never necessitated cessation or interruption of treatment. Several changes in endocrine function took place during treatment: testosterone secretion rate diminished together with the urinary excretion of 17-KS and 17-KGS, while the serum concentration of testosterone binding globulin increased. There was a reduction in the serum concentration of total endogenous estrogens and progesterone as well as LH. No changes in hepatic, renal or hematologic parameters were found except for a slight increase in plasma prothrombin time. Clinical outcome of therapy could not be correlated with a pretreatment endocrine "profile", nor with the changes that this therapy induced in endocrine function. It is concluded that the anti-androgenic effect is probably the most important in this drug regimen, but that reversibility of hirsutism may depend upon factors not directly related to androgen influence.

17-Hydroxycorticosteroids↗

Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne. Results of a multicenter study.

In spite of an abundant literature on antiandrogen treatment with cyproterone acetate (CA) there have been no objectively measured results to prove statistically the possible superiority of CA over combined oral contraceptive pills in the treatment of acne vulgaris. A multicenter study was therefore done, in which two preparations containing CA in combination with ethinylestradiol (EE) were compared with a marketed combined oral contraceptive pill. The preparations studied were: CA 2 mg + EE 50 micrograms (Diane), CA 2 mg + EE 35 micrograms (Diane mite), Levonorgestrel 150 micrograms + EE 30 micrograms (Neovletta). A woman was eligible for the study if she was found by a dermatologist to have at least eight acne lesions (sum of papules, pustules, cysts and nodules) on her face, was otherwise healthy and without medication. After a primary assessment of the number of acne lesions by the dermatologist the woman was referred to a gynecologist and given one of the three test preparations double-blind and at random. The treatment was to continue for 6 months. 133 women were recruited at eight different centers. The groups thus constituted were of similar size and comparable with regard to age, degree of acne, and menstrual and contraceptive histories. As the number of acne lesions varied considerably between patients all data were converted into percentage change during treatment before they were processed in a computer. After only 4 months of treatment the patients on Diane and Diane mite had a significantly greater reduction in the number of acne lesions compared with those on Neovletta.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

Treatment of endometrial hyperplasia with cyproterone acetate histological and hormonal aspects.

A regime of cyproterone acetate (CPA) (300 mg/day by the oral route for 30 days) has been used in 10 post-menopausal women with endometrial hyperplasia (8 atypical and 2 adenomatous). Androstenedione (A), estrone (E1), testosterone (T) and estradiol (E2) plasma levels were determined before and at the end of treatment. The regression of endometrial hyperplasia was ascertained histologically in all patients after 30 days of therapy. All steroids showed a significant decrease (p less than 0.05) as compared with their corresponding basal values. Moreover, the E1/A ratio was significantly lowered (p less than 0.01) following CPA administration (5.9 + 2.9% to 2.5 + 0.6%). From these data it is evident that CPA can not only act as a progestin, but may also reduce the endogenous estrogen production, lowering either the adrenal production of A (the most important estrogen precursor in the post-menopause) or the A to E1 peripheral conversion.

Androgen Antagonists↗