[Comparing the therapeutic effects of spirinolactone plus cyproterone compound with metformin's on polycystic ovarian syndrome]

Polycystic ovarian disease is one of the most common causes of hirsutism, irregular menstruation, obesity, anovulation or infertility in women. More than 50% of these women become obese and 1/3 of them diabetic at a time throughout the life. Metformin is useful to improve the insulin resistance, hirsutism and oligomenorrhea of PCOS patients. Administrating spirinolactone as an androgen antagonist in conjunction with a contraceptive pill such as Cyproterone compound [Dian] may also be effective to treat the sings and complaints of the patients. To compare the efficacy of spirinolactone with cyproterone compound vs. metformin on PCOS. This study was performed on 113 women, 20 to 30 years old, diagnosed to have PCOS, visited in Imam Hosein and Loghman outpatient clinics during three years. They came with complaints such as obesity hirsutism oligomenorrhea or amenorrhea Metformin is effective in improving obesity, hirsutism and oligomenorrhea of obese PCOS patient [regardless of their insulin resistance] [P< 0.005]. Metormin is more effective to reduce the body weight in obese women than those two [P< 0.05], on the other hand it has a limited effect on the hirsutism and oligomenorrhea of non-obese PCOS patients. Spirinolactone in conjunction with Dian is effective in improving the hirsutism, obesity and oligomenorrhea of the obese [regardless of their insulin resistance] [p< 0. 05] and non-obese patients [p< 0.005]. Metformin is more effective than Spirinolactone together with Dian on weight reduction in obese PCOS [p< 0.005], and Spirinolactone together with Dian is more effective on hirsutism and oligomenorrhea of non-obese patients than Metformin alone [p< 0.05]. Metoformin is effective to treat the obesity, hirsutism, and oligomenorrhea of the obese women and the combination of spirinolactone and cyproterone compound is more effective to treat hirsutism and oligomenorrhea in non-obese women with PCOS

Advantages of Chinese medicine for treatment of blood sugar and lipid metabolic disorders in patients with polycystic ovarian syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>CM is effective for the treatment of PCOS in improving insulin resistance, adjusting blood sugar and lipids levels and recovering ovulation.</p>

A case of fulminant hepatic failure due to cyproterone acetate in a patient with cryptogenic liver cirrhosis / 대한내과학회지

Cyproterone acetate is an antiandrogenic drug that has been used in prostatic cancer. The drug is thought to be well-tolerated but has hepatotoxic effects. An 89 year-old man treated with cyproterone acetate 300 mg/d for prostatic cancer presented with a hepatotoxic reaction. Toxic hepatitis was diagnosed and cyproterone acetate was stopped immediately. The patient was treated with supportive management and a corticosteroid, but he died 28 days after administration due to liver failure. A liver biopsy performed after his death revealed the presence of acute hepatitis with cirrhosis. Underlying cirrhosis was not suspected before his death. Ultimately, the case was diagnosed as fulminant hepatic failure due to cyproterone acetate with underlying cryptogenic liver cirrhosis. This case and current literature highlight the hepatotoxic potential of cyproterone acetate and illustrate the importance of clinical surveillance, especially in patients with unrecognized liver disease.

Male contraception: expanding reproductive choice.

The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable, safe and effective male contraceptive, scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen, thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently, a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view, while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men, using sperm surface epitopes not expressed in female reproductive tract as source, still requires considerable research efforts.

Supresión versus modificación del antiandrógenos ciproterona en la progresión del cáncer de próstata / Antiandrogen withdrawal versus change of ciproterone in relapse prostate cancer

Objetivo: Analizar las respuestas en la concentración del antígeno prostático específico (APE) y en la clínica. en pacientes hormorrefractarios al bloqueo androgénico con ciproterona más aginistas LHRH, que hubieran tenido una respuesta positiva de al menos 6 meses con la primer línea terapéutica, al suprimir la ciproterona o bien reemplazarla por bicalutamida. Material y Métodos: Se randomizaron 12 pacientes para suprimir en 6 de ellos la ciproterona o reemplazarla con bicalutamida en los otros 6., determinándose entonces la concentración sérica mensual de APE y la respuesta clínica subjetiva. Resultados: en 7 pacientes (4 del grupo que suprimió ciproterona y 3 del que reemplazó con bicalutamida) la concentración sérica del APE se redujo entre 38,4 y 82,2 por ciento, observándose una respuesta clínica satisfactoria en los 5 pacientes de este grupo que eran sintomáticos. Tres de los pacientes continuaron progresando (2 del grupo con bicalutamida) tanto en valores de de APE cuanto en la evaluación del dolor. Los pacientes con respuestas favorables habian tenido una respuesta a la primera línea del tratamiento entre 17 y 58 meses (media 37,8 meses) y el Gleason promedio fue 5,1 (rango 3 a 7). Los pacientes en los que observamos progresión tuvieron una respuesta positiva a la primera línea del tratamiento entre 10 y 15 meses (p`romedio 12,3 meses) y el Gleason promedio fue de 8,66 (rango 8 a 9). Conclusiones: Hemos observado respuestas en pacientes con cáncer de próstata refractario a la terapia combinada con agonistas LHRH más ciproterona tanto en los que se suprimió la coproterona como en los que se reemplazó al antiandrógeno por bicalutamida. La respuesta positiva parece estar ligadaal Gleason inicial y al tiempo de respuesta a la primeralinea terapéutica en menos de 15 meses y con Gleason mayor de 8 no respondieron a ninguna de las variantes de supresión o remplazo. Al momento, no podemos determinar cuál de las 2 ramas de tratamiento (remplazo o supresión) resulta más eficaz

Intermittent Androgen Deprivation(IAD) with Cyproterone Acetate Monotherapy for Prostate Cancer: A preliminary report / 대한비뇨기과학회지

PURPOSE: The purpose of this study was to evaluate the feasibility of using IAD, as a steroidal antiandrogen (cyproterone acetate) monotherapy, for prostate cancer. MATERIALS AND METHODS: A total of 43 prostate cancer patients (Stage A to C in 27, D1 in 2 and D2 in 14) were reviewed. Androgen deprivation, with cyproterone acetate (200-300mg P.O/day), was continued until a serum prostate specific antigen (PSA) nadir was maintained for at least 3 months. Medication was then discontinued until the serum PSA reached a predetermined level. This cycle of treatment was repeated until there was a continual increase in the PSA irrespective of the medication. RESULTS: The mean observation period was 10.5 months, ranging from 4 to 28 months. In seven of the 43 patients, there was treatment failure before entering the off-treatment period of the 1st cycle. 17 of the remaining 36 patients completed the on-treatment during cycle 1, with a median time to PSA nadir of 4 months. Seven patients completed cycle 1, with a median time off-treatment of 5 months (43% of the treatment cycle). Nineteen patients are still in the on-treatment intervals and 10 in the off-treatment intervals of their first cycles. Two patients completed the on-treatment of the 2nd cycle, with a median time to PSA nadir of 2.5 months. During the off-treatment interval, most patients reported an improvement in the symptoms associated with androgen suppression. CONCLUSIONS: IAD, using cyproterone acetate monotherapy, is a feasible alternative for continuous androgen deprivation in the treatment of prostate cancer. It also results in the reduction of toxicity, cost of treatment and possibly a delay in the tumor progression.

Comparison of norgestrel- versus cyproterone acetate-containing hormone replacement therapy on lipid-lipoprotein metabolism.

To compare the effects on the lipid profile of estradiol valerate with norgestrel to a regimen of estradiol valerate with cyproterone acetate. Sixty-four healthy women in their perimenopause or early postmenopause, aged between 40-55 years, were randomized to one of the two 21-day sequential regimens: estradiol valerate 2 mg/day for 21 days and combined with either norgestrel 0.5 mg/day or cyproterone acetate 1 mg/day from day 12 to 21, with 7 days of drug-free interval, for 12 cycles. Lipid profiles were followed at baseline, 6 and 12 cycles. Sixty-one subjects completed the study, 30 in the norgestrel group and 31 in the cyproterone group. During 12 cycles of study, serum HDL cholesterol levels decreased significantly in the norgestrel group (p < 0.01) and were unchanged in the cyproterone group. The levels were significantly lower in the norgestrel group than in the cyproterone group (p < 0.05). No differences were found between groups as regards LDL cholesterol and total cholesterol levels. Triglyceride levels decreased significantly in the norgestrel group (p < 0.01), remained unchanged in the cyproterone group and the levels were significantly different between groups (p < 0.01). In conclusion, the study demonstrated that sequential regimen of estradiol valerate with norgestrel produced less favorable HDL cholesterol but more favorable triglyceride levels than the regimen of estradiol valerate with cyproterone acetate.

Efectos del valerato de estradiol ciproterona sobre el síndrome climaterio y parámetros bioquímicos en mujeres chilenas / Effects of estradiol valerate and ciproterone acetate on climateric syndrome and biochemical parameters in Chilean women

La menopausia se asocia a un demostrado aumento del riesgo de enfermedad cardiovascular y de osteoporosis, lo que justifica el uso de terapia hormonal de reemplazo. Como ésta se plantea por tiempo prolongado, debe ser efectiva en prevenir las complicaciones y en suprimir el síndrome climatérico. Se estudió la eficacia de la asociación de valerato de estradiol (VE) y acetato de ciproterona (CPA) en la reducción de los síntomas asociados a menopausia. Se analizaron, prospectivamente, 342 mujeres durante 6 meses, consignando la intensidad de sus síntomas y los cambios en peso, presión arterial y parámetros bioquímicos. Las oleadas de calor, así como otros síntomas y signos, disminuyeron en intensidad. No hubo diferencia significativa en la evolución del peso ni de la presión arterial, aunque sí en algunos parámetros del perfil lipídico y hepático. Se concluye que la asociación VE y CPA reduce la intensidad de los síntomas climatéricos en el grupo estudiado

Hirsutismo - tratamento / Treatment of hirsutism

O hirsutismo representa uma patologia de grande importância para os médicos ginecologistas, näo só pela sua expressiva incidência e pelo aspecto emocional que envolve as pacientes, mas também pela baixa aderência ao tratamento que deve ser a longo prazo.

Blockade of the in vitro effects of testosterone and erythropoietin on Cfu-E and Bfu-E proliferation by pretreatment of the donor rats with cyproterone and flutamide

Erythropoietin is obligatory to support the terminal proliferation and differentiation of erythroid cells but it is not the only agent in modulating red cell production. Previously, we have shown that Testosterone enhances erythropoiesis, at least in part, by increasing renal erythropoietin production. Testosterone may also influence directly the behavior of the erythroid progenitor cells increasing erythroid stem cell proliferation. To gain further insight into the role of testosterone in regulation of erythropoiesis and its interactions with erythropoietin, we studied the effect of testosterone and erythropoietin, using clonal cultures of erythropietic progenitors, to observe CFU-E and late and early BFU-E colonies proliferation from bone marrow cells of donor rats pretreated for 2 days with the androgen antagonists cyproterone (10 mg/Kg/day) and flutamide (160 mg/Kg/day). Specific nuclear receptors for testosterone were demonstrated in marrow erythroid cells. Then, erythroid progenitors may come with their androgen receptors blocked by pretreatment. Cultures were prepared using the methylcellulose technique containing a standard dose of erythropoietin (250 mu/ml) or testosterone (10(-7) M). Results obtained demonstrate that testosterone produced a significant stimulation on CFU-E and BFU-E colony formation. A dose effect correlation was apparent. Testosterone enhances proliferation of late BFU-E more than CFU-E and produce only a slight augmentation of early BFU-E. As expected, erythropoietin markedly stimulate all erythroid colony growth, mainly CFU-E. The effects of testosterone were completely abolished in cultures from bone marrow cells of rats pretreated with cyproterone and flutamide. Activation of the specific androgen nuclear receptors in erythroid cells appears to be necessary for testosterone to develop the erythropoietic effect. Surprisingly, the effects of erythropoietin on erythroid colonies proliferation were also completely blocked by pretreatment with flutamide and partially blocked by pretreatment with cyproterone. Right now, we do not have a satisfactory explanation regarding inhibition of the effects of erythropoietin by pretreatment to marrow donor rats with the androgen antagonists. In conclusion, we postulate triggering late BFU-E cells, a marrow erythropoietin responsive cell population, into active cell cycle, as well as by increasing blood erythropoietin concentration.

Hirsutismo: experiencia en diagnóstico y tratamiento en el período 1970-1995 / Hirsutism: experience in diagnosis and treatment in the period 1970-1995

En la anamnesis de la hirsuta, destaca el inicio peripuberal del hirsutismo y en el examen físico la importancia del vello pubiano que aporta el 40 por ciento del score total. Del 74 por ciento de hirsutas hiperandrogénicas, el 34 por ciento poseen elevación exclusiva de la testosterona, el 24 por ciento de la dehidroepiandrosterona sulfato y el 42 por ciento un alza de ambas. El alto porcentaje de dehidroepiandrosterona sulfato aumentada, sola o junto a testosterona, sugiere un compromiso suprarrenal en la etiología del hirsutismo, respaldado por un 50 por ciento de prueba de estimulación suprarrenal con hiperrespuesta de este andrógeno, en hirsutas y en pacientes con síndrome de ovario poliquístico. El alza de la 17 hidroxiprogesterona basal, obliga a realizar prueba de estimulación cob ACTH para descartar su origen ov+arico y confirmar el déficit de la 21 hidroxilasa. Un 5 por ciento de las hirsutas tenían acantosis nigricans con resistencia insulínica y alteraciones lipídicas. Se analiza el tratamiento con antiandrógenos, ciproterona y espironolactona y la frenación con glucocorticoides

Therapeutic alternatives for the hirsute woman

A retrospective analysis of 21 hirsute women seen at a gynecological endocrine clinic revealed a high incidence of infertility, menstrual irregulaties and abnormal androgen profile. Polycystic ovarian syndrome (PCOS) was the underlying abnormality in the majority of cases. Cyproterone acetate (CPA) with ethinyl oestradiol in a reverse sequential regime was more effective and better tolerated but much more expensive than the combination of spironolactone and the oral contraceptive pill (OCP).

Clinical and hormonal studies in precocious puberty.

Data from 31 children, 23 females (74.2%) and eight males (25.8%) with precocious puberty were analysed. They included 19 cases with central precocious puberty, 5 with premature thelarche, 5 with premature adrenarche and 1 each with adrenal adenoma and virilizing hepatoblastoma. Their clinical and hormonal profile and the treatment outcome are briefly discussed.

Effect of cyproterone acetate on testis of albino rats: ultrastructural and biochemical approach.

The animals were treated with cyproterone acetate (1 mg/100 g body weight) for 60 days after which the testicular tissue was studied at the ultrastructural level to determine the stage at which the effect took place and to study the magnitude of the effect. The testis showed changes in Sertoli cells, Leydig cells, germ cells and in the spermatids. To correlate these changes, important marker enzymes and other biochemical parameters essential for spermatogenesis were studied after 30 days and 60 days of the treatment. They registered a decrease in their levels as compared with the controls.