Differential Effects of Cyproterone Acetate vs Spironolactone on Serum High-Density Lipoprotein and Prolactin Concentrations in the Hormonal Treatment of Transgender Women.

INTRODUCTION: Spironolactone and cyproterone acetate (CPA) are the two main antiandrogen medications used in feminizing hormone therapy in transgender women. Previous studies have suggested that these two agents might have opposite effects on high-density lipoprotein (HDL) level when used in this context, and limited data have suggested CPA increases prolactin more than spironolactone. AIM: To compare the effects of spironolactone and CPA on HDL and prolactin serum concentrations in transgender women. METHODS: A retrospective chart review was conducted at three clinical sites in Toronto, Ontario, Canada. Patients were selected if they (i) identified as a transgender woman, (ii) had newly started spironolactone or CPA with estrogen or restarted spironolactone or CPA after a washout period of at least 6 months, and (iii) had not used other antiandrogens within the previous 6 months. MAIN OUTCOME MEASURES: HDL and prolactin concentrations between the two treatment groups at baseline and at 12 months. RESULTS: Eighty-two patients were included in the spironolactone group and 31 patients were included in the CPA group. Baseline HDL and prolactin levels were not significantly different between the two groups. At 12 months, HDL increased by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07 mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained significant after adjusting for baseline HDL, use of lipid-lowering drugs, and age. The change in prolactin was +3.10 µg/L (SD = 5.70) in the spironolactone group and +11.8 µg/L (SD = 8.63) in the CPA group (P < 0.001). This difference also remained significant after adjusting for baseline prolactin level. CONCLUSION: These data suggest that spironolactone use in transgender women increases HDL levels and that CPA has the opposite effect. CPA also is associated with a larger increase in prolactin. These factors should be considered when choosing between these two antiandrogen agents.

Hormonal treatment reduces psychobiological distress in gender identity disorder, independently of the attachment style.

INTRODUCTION: Gender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic-pituitary-adrenal system dysregulation and subjective stress. AIM: The objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. METHODS: We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. MAIN OUTCOME MEASURES: We used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self-reported perceived stress and the Adult Attachment Interview to determine attachment styles. RESULTS: At enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P < 0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P < 0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P < 0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. CONCLUSION: Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be.

First-line treatment of metastatic prostate cancer. Androgen suppression for symptomatic disease.

Prostate cancer sometimes metastasizes, especially to bone, which may cause pain, fractures and spinal cord compression. What are the best first-line treatment options for patients with metastatic prostate cancer? To answer this question, we conducted a review of the literature, using the standard Prescrire methodology. Suppressing androgen secretion by surgically removing the testicles (orchiectomy) or by administering a gonadorelin agonist relieves the pain associated with bone metastases in about 80% of patients. This treatment has a clear impact on symptoms, despite the lack of clinical trials versus placebo or no treatment. Its impact on overall survival is uncertain. In terms of survival, goserelin therapy appears to have similar efficacy to orchiectomy. The efficacy of other gonadorelin agonists is less well documented. Degarelix, a gonadorelin antagonist, does not appear to provide a therapeutic advantage over gonadorelin agonist. In 2012, oestrogen should not be used in the treatment of metastatic prostate cancer, because of its cardiovascular adverse effects. Antiandrogen monotherapy, preferably with flutamide, appears to be less beneficial than orchiectomy in terms of survival. Overall, adverse effects are more frequent with nonsteroidal antiandrogens than with gonadorelin agonists, but sexual dysfunction is less frequent. Cyproterone, a steroidal antiandrogen, seems to have fewer adverse effects leading to treatment discontinuation than nonsteroidal antiandrogens. There is no firm evidence that starting hormonal therapy before metastases become symptomatic is beneficial. When symptoms have disappeared and the PSA level is low, one option is to temporarily interrupt gonadorelin agonist therapy if it is poorly tolerated, even though this may shorten survival by a few months. The addition of a nonsteroidal antiandrogen to androgen suppression therapy slightly improves 5-year survival, preventing about 3 deaths per 100 patients, but at a cost of additional adverse effects. First-line hormonal treatments are initially very effective in relieving symptoms of metastatic prostate cancer. Our analysis of the available data suggests that the best treatment option is androgen suppression with goserelin. Flutamide monotherapy is an alternative for some patients.

Pharmacological treatment of behavioural and psychological symptoms of dementia in psychogeriatric inpatient units.

OBJECTIVE: This study involved an examination of the current patterns of pharmacological treatment of patients with behavioural and psychological symptoms of dementia (BPSD) in psychogeriatric inpatient units. METHOD: An audit was conducted of discharge medications of patients with BPSD who were hospitalized at three separate inpatient units in Perth, Western Australia over a 1-year period. RESULTS: Prescribing patterns were found to be relatively similar across the three units. Dementia-specific drugs such as choline-esterase inhibitors and memantine comprised a minority of prescribed medication. Antipsychotics, benzodiazepines and sodium valproate were the most commonly prescribed drugs. Cyproterone acetate was used in a small number of patients at each of the three units. CONCLUSIONS: The broad range of medications used to treat BPSD, the relatively modest place of dementia-specific drugs in this patient group, and the co-prescribing of more than one psychotropic agent in the majority of patients support the prevailing impressions that BPSD are difficult to treat and that there is no consistently effective or superior medication or drug group.

[Advantages of Chinese medicine for treatment of blood sugar and lipid metabolic disorders in patients with polycystic ovarian syndrome].

OBJECTIVE: To study the advantages of Chinese medicine (CM) in treating insulin resistance and disorders of glucose and lipid metabolism in patients with polycystic ovarian syndrome (PCOS), and to explore its underlying mechanisms. METHODS: One hundred PCOS patients were assigned to three groups: 40 patients in the CM group treated by CM, 30 in the WM1 group treated by metformin, and 30 in the WM2 group treated by cyproterone. Before treatment and at 3 cycles and 6 cycles after treatment, changes of body mass index (BMI), fasting serum insulin (FINS) and fasting blood sugar (FBG) levels as well as lipid spectrum were measured and the homeostasis model of insulin resistance (HOMA-IR) was calculated. Meanwhile, the recovery of ovulation was observed. RESULTS: There were 30, 22 and 23 patients in the CM, WM1 and WM2 group respectively completed their 6-month treatments. Levels of FINS, FBG, HOMA-IR, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were lowered and high-density lipoprotein cholesterol (HDL-C) level increased in the CM group after 6-month treatment, showing significant difference as compared with the baseline (P < 0.05), and the difference in comparing with the WM2 group was statistically significant in terms of MBI, FINS, FBG, HOMA-IR, TC and LDL-C (P < 0.05). The ovulation rate was 53.3% (16/30) in the CM group, 27.3% (6/22) in the WM1 group and 21.7% (5/23) in the WM2 group, comparison between them showed a significant difference between the CM group and the WM2 group (P < 0.01). CONCLUSION: CM is effective for the treatment of PCOS in improving insulin resistance, adjusting blood sugar and lipids levels and recovering ovulation.

Anti-androgenic therapy in young patients and its impact on intensity of hirsutism, acne, menstrual pain intensity and sexuality - a preliminary study.

OBJECTIVES: Using anti-androgenic contraception is one of the methods of birth control. It also has a significant, non-contraceptiveimpact on women's body. These drugs can be used in various endocrinological disorders, because of their abilityto reduce the level of male hormones.The aim of our study is to establish a correlation between taking different types of anti-androgenic drugs and intensity ofhirsutism, acne, menstrual pain intensity and sexuality. MATERIAL AND METHODS: 570 women in childbearing age that had been using oral contraception for at least three monthstook part in our research. We examined women and asked them about quality of life, health, direct causes and effects ofthat treatment, intensity of acne and menstrual pain before and after. Our research group has been divided according tothe type of gestagen contained in the contraceptive pill: dienogest, cyproterone, chlormadynone and drospirenone. Additionally,the control group consisted of women taking oral contraceptives without antiandrogenic component. RESULTS: The mean age of the studied group was 23 years ± 3.23. 225 of 570 women complained of hirsutism.The mean score for acne intensity before the use of contraception was 2.7 ± 1.34. The mean score for acne intensity after3 months of using contraception was 1.85 ± 1.02 (p < 0.001). 192 women reported excess hairiness in one or more areabefore treatment. Mean value based on Ferriman-Gallway scale before the treatment was 6.23 ± 6.21 and 5.39 ± 5.6 afterthe treatment (p < 0.001). CONCLUSIONS: All groups of drugs effectively reduced pain and acne severity. Cyproterone and drospirenone turned outas the most effective drugs in treating hirsutism. Surprisingly, according to our research, dienogest does not have anyimpact on body hairiness.

Evaluation of resistance index in patients with prostate cancer.

BACKGROUND: The purpose of this study was to evaluate the relationship of the resistance index (RI) of the prostate measured by transrectal ultrasonography (TRUS) in Taiwanese prostate cancer patients to Gleason score, staging and prostate volume. PATIENTS AND METHODS: Forty-five patients (mean age, 73.3 years; range 56 to 97) diagnosed to have prostate cancer via prostate biopsy and/or transurethral prostatectomy were recruited for our study. The patients were divided into 3 groups according to Gleason score, low grade (2-4, LG n = 14), intermediate grade (5-7, IG n = 14) and high grade (8-10, HG n = 17) groups. The blood flow pattern and mean RI of the prostate vessels were recorded and compared with age, prostate volume, serum prostate specific antigen (PSA) and oncological stage. A follow-up color Doppler ultrasonography was also performed in 17 patients after 3-6 months of hormone therapy and the changes of RI were recorded. RESULTS: The mean age, serum PSA and prostate volume were comparative among the three groups, but the differences of RI were statistically significant (p = 0.029). Advanced prostate cancer (HG group) tended to have higher RI. There was a close correlation between RI and Gleason score (Spearman R = 0.452, p = 0.002). The high RI phenomenon could be reversed after 3-6 months of hormone therapy (paired t-test, p < 0.05). CONCLUSION: High grade prostate cancer tends to have higher RI. RI measurement during color Doppler TRUS may be helpful in the evaluation of the vascularity of prostate cancer and its vascular changes to hormone treatment.

[Efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproterone and desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome].

OBJECTIVE: To evaluate the efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproteroneand desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome (PCOS). METHODS: Women with PCOSfrom West China Second Hospital of Sichuan University enrolled between September, 2011 and August, 2013 were randomlyallocated to receive either ethinyl oestradiol/cyproterone tablets (Group A, n=355) or desogestrel/ethinyl oestradiol tablets(Group B, n=357) for a prospective observation period of 6 months. Women with insulin resistance also received metformin. Atbaseline, 3 months, and 6 months, the patients were evaluated for menstruation, acne score, body mass index (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian volume, and the number of ovarian follicles. RESULTS: All the patients had a regular menstrual cycle aftertreatments. Testosterone level, acne score, LH/FSH, ovarian volume, and the number of follicles decreased significantly afterthe treatments without significant differences between the two groups. Significant increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as compared with group B (P < 0.001). FPG decreased in both groups, and wassignificantly lower in group B at 6 months (P < 0.05). BMI and WHR decreased in all the patients with insulin resistance aftercombination treatment with metformin (P < 0.05), but increased significantly in patients without insulin resistance (P < 0.05). Ingroup A, HOMA- IR significantly increased in patientswithout insulin resistance at 3 months (P < 0.05), whereas asignificant increase was not observed until 6 months ingroup B (P < 0.05). CONCLUSIONS: Both ethinyl oestradiol/cyproterone tablets and desogestrel/ethinyl oestradioltablets can relieve the symptoms of PCOS, but it isadvisable to assess the risk of cardiovascular diseasebefore the treatments.

Hormonally responsive versus unresponsive progression of prostatic cancer to antiandrogen therapy as studied with the Dunning R-3327-AT and -G rat adenocarcinomas.

The present study has compared the response to antiandrogen therapy of the serially transplantable Dunning R-3327-AT (hereafter called AT) versus Dunning R-3327-G (hereafter called G) rat prostatic adenocarcinoma. Castration or chemical antiandrogen therapy (i.e., cyproterone acetate and diethylstilbestrol) of rats bearing established AT or G tumors results in neither regression of tumor volume nor a cessation of the continuous growth of either tumor. By these criteria, both the AT and G tumors progress following antiandrogen therapy. For the AT tumor, this progression is completely unresponsive to hormonal therapy, and thus such therapy does not increase survival of AT tumor-bearing rats. The AT tumor is therefore an example of hormonally unresponsive progression. In direct contrast, while the G tumor likewise progresses following antiandrogen therapy, this therapy does induce a 1.8-fold decrease in the subsequent growth rate of the G tumor. This positive response during progression of the G tumor results in a 78% increase in the survival of G tumor-bearing rats treated with antiandrogen therapy. The G tumor is therefore an example of hormonally responsive progression. These results indicate neither that prostatic cancers which do not regress or cease growing following antiandrogen therapy can necessarily be considered hormonally unresponsive nor that antiandrogen therapy of such tumors has been completely ineffective, since, as shown in the present study, such progression can be of either a hormonally unresponsive or a responsive type. Regardless of which type of progression occurs, however, additional therapy is required to further increase survival. The present study demonstrates that such additional therapy should probably not include the subsequent use of pharmacological doses of exogenous androgen, since, depending on the type of progression, such treatments can actually decrease survival.

Effectiveness of complete versus partial androgen withdrawal therapy for the treatment of prostatic cancer as studied in the Dunning R-3327 system of rat prostatic adenocarcinomas.

Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.

[Preliminary pilot study of cyproterone acetate for the treatment of aggressive behavior associated with severe dementia]. / Etude pilote préliminaire de l'acétate de cyprotérone dans les comportements agressifs associés aux démences sévères.

INTRODUCTION: Behavioral symptoms are common in dementia, and seem to be more frequent in men than in women. Agitation is frequently responsible for caregiver burn-out and leads to institutionalization. The dramatic increase in the prevalence of Alzheimer's disease and related disorders requires better management of behavior symptoms. Although environmental adaptation has been proposed recently, for many years, psychoactive medications and physical restraints were the primary approach. However, in severely demented patients, both pharmacologic and non-pharmacologic treatments are inoperative. In this situation, alternative pharmacologic approach should be tested. Cyproterone acetate, an antiandrogen and progestative steroid has never been proposed to prevent aggressive behavior in dementia, but its favorable effect is well described in rat and monkey aggressivity. PATIENTS AND METHODS: Cyproterone acetate was proposed for 19 demented patients who developed severe aggressive behaviors or an agitation unresponsive to psychoactive drugs (even in association) or to environmental adaptation. Clinical and behavioral analysis was carried out using the Cohen-Mansfield agitation inventory associated with an assessment of dependency in daily life activities, before and during treatment with cyproterone acetate. The behavioral status was stable, with permanent or repetitive agitation. Seven patients had vascular dementia, 7 had Alzheimer's disease, 2 had fronto-temporal degeneration, 2 had Huntington's disease and 1 a probable diffuse Lewy bodies disease. Fifteen patients had prominent aggressive behavior and 4 had predominant aberrant motor behavior with aggressive behavior. RESULTS: Cyproterone (50 to 100mg - mean: 92.5mg daily) improved significantly aggressive and impulsive behavior related to Alzheimer's disease or vascular dementia but had no effect on aberrant motor behavior. When cyproterone was stopped, aggressive behaviors reappeared more rapidly in vascular dementia. CONCLUSION: Cyproterone acetate is then an interesting choice when aggressive behavior is not improved with psychotropic drugs. A detailed clinical analysis is required to avoid the use of cyproterone in non-aggressive and non-impulsive patients. The results of this preliminary study suggest a randomized double-blind study should be carried out in the near future. The behavior improvement could be related to the blockage of androgen receptors, and simultaneously to the sedative effect of progestative drugs.

The cyproteronacetat treatment of sexual offenders.

Anti-hormonal treatment of sexual offenders with Cyproteronacetat is discussed. The authors report on their own findings, and review the literature. They believe that Cyproteronacetat in combination with supportive psychotherapy is a promising modality. They further comment on the Austrian legal situation.

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.

Plasma lipoproteins during treatment with cyproterone acetate in men with prostatic carcinoma.

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated by estrogens. The antiandrogenic gestagenic drug, cyproterone acetate, is sometimes used instead of estrogens in the treatment of prostatic cancer. The cardiovascular risk associated with such hormonal treatment has been debated. Changes in plasma lipoproteins are related to the risk of cardiovascular disease and can be brought about by hormonal treatment. Plasma lipoproteins were therefore investigated during cyproterone acetate therapy in 15 men with prostatic cancer. Cholesterol (C), triglyceride, and phospolipid (PL) concentrations were determined in the very low density, low density (LDL), and high density lipoprotein (HDL) fractions. During treatment, mean body weight decreased by 1.2 and 1.9 kg after 2 and 8 weeks, respectively. The mean C concentration was lowered by 16%. The HDL C was reduced by a mean of 25%, and the LDL C decreased by means of 15% and 10%. The part of plasma C carried in the HDL fraction decreased slightly from 19 to 17% (mean) and the mean HDL C/LDL c quotient was lowered from 0.27 to 0.22. The mean PL concentration in plasma was decreased due to a mean reduction of HDL-PL by 17% and LDL Pl by 10%. A reduction of the HDL/LDL quotient implicates an increased risk for development of atherosclerotic diseases. However, it seems unlikely that a modest reduction in the HDL/LDL quotient, as obtained by cyproterone acetate, should have any great influence on the incidence of cardiovascular disease in elderly men with prostatic carcinoma.

Hyperprolactinemia in girls with idiopathic precocious puberty under prolonged treatment with cyproterone acetate.

Pasma prolactin response to the acute injection of sulpiride (1.5 mg/k BW im) was measured at 0800-0900h in 4 girls with idiopathic precocious puberty before and after 6 to 11 months of continuous therapy with 50 mg daily of cyproterone acetate (CA) orally administered. Two additional girls were examined after 26 and 28 months of therapy, respectively. Mean baseline prolactin concentrations were significantly higher in untreated girls with precocious puberty as compared to that of normal controls of the same chronological age and of a comparable degree of sexual maturation (14.5 +/- 1.9 SE vs. 7.4 +/- 1.8 SE ng/ml and vs. 9.5 +/- 1.8 ng/ml, respectively; P less than .02). Treatment with CA caused a significant further increase of plasma prolactin concentration (P less than .02 as compared to pre-treatment values); no correlation was observed between prolactin concentration and duration of treatment. No significant change in the integrated areas of prlactin response to sulpiride occurred after prolonged CA therapy. The results suggest that in idiopathic precocious puberty the action of CA upon the hypothalamic-hypophyseal complex is not solely antigonadotropic and that prolactin secretion is enhanced in patients given this drug.

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.

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.

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.

Effect of cyproterone acetate therapy on gonadotropin response to synthetic luteinizing hormone-releasing hormone (LRH) in girls with idiopathic precocious puberty.

50 mg daily of cyproterone acetate (CA) were orally administered for 8 to 35 months to 7 girls with idiopathic precocious puberty. Plasma levels of FSH and LH, cortisol, testosterone, estradiol, and progesterone were measured in 6 patients before treatment. Compared with control subjects of the same chronological age, significantly higher values were found for gonadotropins, testosterone, and estradiol. After treatment, no significant variation was observed in FSH and LH levels; testosterone was reduced in the majority of the cases without significant decline in mean values; estradiol fell significantly and returned in the prepubertal range. The plasma gonadotropin pattern following exogenously administered luteinizing hormone-releasing hormone (LRH, 100 mug iv) was characterized before treatment by an exaggerated LH response both in terms of maximum level (32.02 +/- 4.35 SE mIU/ml; prepubertal controls: 16.20 +/- 1.45 SE mIU/ml) and maximum increment above baseline values (25.36 +/- 2.84 SE mIU/ml; prepubertal controls: 13.78 +/- 1.71 mIU/ml); plasma FSH response was similar to prepubertal subjects. Treatment with CA caused a significant reduction of mean LH response (P less than .025 in comparison with pre-treatment values for maximum level and maximum increment), whereas effect on FSH response was minimal. In all patients examined, a gonadotropin release from the pituitary after the injection of synthetic LRH was evident also after several months of therapy.