Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women.

OBJECTIVE: The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy with or without cyproterone acetate in transgender women. METHODS: The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate. The daily dose of conjugated equine estrogen was 0.625 mg in 41 subjects and 1.25 mg in 10 subjects, and the daily dose of cyproterone acetate was 50 mg in 42 subjects and 100 mg in one subject. RESULTS: Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 731.5 to 18 ng/dL, 6.3 to 1.1 U/L and 9.6 to 1.5 U/L, respectively. Estrogen plus cyproterone acetate reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 750 to 21 ng/dL, 6.8 to 0.6 U/L and 10 to 1.0 U/L, respectively. The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different. The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen alone and estrogen plus cyproterone acetate. CONCLUSION: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.

Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women

OBJECTIVE: The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy with or without cyproterone acetate in transgender women. METHODS: The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate. The daily dose of conjugated equine estrogen was 0.625 mg in 41 subjects and 1.25 mg in 10 subjects, and the daily dose of cyproterone acetate was 50 mg in 42 subjects and 100 mg in one subject. RESULTS: Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 731.5 to 18 ng/dL, 6.3 to 1.1 U/L and 9.6 to 1.5 U/L, respectively. Estrogen plus cyproterone acetate reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 750 to 21 ng/dL, 6.8 to 0.6 U/L and 10 to 1.0 U/L, respectively. The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different. The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen alone and estrogen plus cyproterone acetate. CONCLUSION: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.

Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases.

BACKGROUND & AIMS: Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI. METHODS: Twenty-two males (70 ± 8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150 ± 50 mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed. RESULTS: From 1993 to 2013, 22 patients were retrieved. Latency was 163 ± 97 days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18 ± 13 × ULN, ALP 0.7 ± 0.7 × ULN and total serum bilirubin 14 ± 10 mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%). CONCLUSIONS: CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient.

Tratamento hormonal do hirsutismo baseado em evidências / Evidence-based hormonal treatment of hirsutism

A revisão de estudos baseados em evidências mostra o melhor tratamento hormonal para o hirsutismo. Inicialmente, resumiu-se a fisiologia do pelo, caracterizou-se o hirsutismo, suas variantes e suas causas. Revelou-se que o tratamento hormonal do hirsutismo deve ser complementado pelo tratamento cosmético e não deve ser indicado para mulheres grávidas ou que desejam engravidar. A primeira opção é o contraceptivo hormonal oral, seguro para contracepção e eficaz para tratamento do hirsutismo. Após tempo estipulado, não ocorrendo resposta satisfatória, associar acetato de ciproterona ou espironolactona. A finasterida é indicada para hirsutismo idiopático e a flutamida, devido aos efeitos colaterais, ainda não é opção segura

An evidence-based review shows the best hormonal treatment of hirsutism. This paper summarized the physiology of the hair, characterized the hirsutism, its variants and etiologies. The study revealed that hormonal treatment of hirsutism has to be complemented by esthetic treatment, and it is not recommended for pregnant women or for those who want to get pregnant. The first option is hormonal oral contraceptive, which is safe for contraception and effective for treatment of hirsutism. After a established period of treatment, if good results do not occur, the association of cyproterone or spironolactone is recomended. Finasteride is the treatment of idiopathic hirsutism, and flutamide is not a safe option due to its side effects

Ethinylestradiol/cyproterone acetate in polycystic ovary syndrome: lipid and carbohydrate changes.

OBJECTIVE: Ethinylestradiol (EE) combined with the antiandrogenic progestin cyproterone acetate (CPA) is a possible treatment in polycystic ovary syndrome (PCOS). We investigated the impact of EE/CPA on lipid and carbohydrate metabolism in women with PCOS,who were otherwise healthy. METHOD: The 31 women were separated into two groups paired by body mass index (BMI): Group A (control, n = 15) were cycled with 10 mg medroxyprogesterone acetate (MPA) x 10 days (Provera, Pharmacia & Upjohn) every month for 3 months; Group B (n = 16) were treated with 35 microg EE/2 mg CPA (Diane 35, Schering) for 3 months. Metabolic and hormonal conditions were similar in both groups. RESULTS: Group A showed no change in any hormone or metabolic parameter. Group B showed a significant decrease in free androgen index (-81%) and increase in sex hormone binding globulin (+ 639%), a decrease in low density lipoprotein cholesterol (-14%) and total cholesterol/high density lipoprotein (HDL) cholesterol index (-19%), and increases in HDL cholesterol (+ 23%) and triglycerides (+ 82%) (p < 0.001). Fasting insulin increased in 18%, the glucose/insulin index worsened in 8%, and the plasma glucose disappearance worsened in 12%, with no statistical significance (p= 0.092, p=0.308 and p= 0.237, respectively). CONCLUSION: Treatment of PCOS with EE/CPA induces important favorable changes regarding hormone parameters associated with hyperandrogenism, significant favorable changes in lipid profile except for triglyceride increase, and no significant change in carbohydrate metabolism (measured by fasting insulin, glucose/insulin index and plasma glucose disappearance). MPA cycling does not change any of these parameters.

Cáncer de próstata: bloqueo androgénico intermitente / Prostatic cancer: intermittent androgen blockade

El cáncer de próstata (CP) constituye un grave problema de salud pública. Su incidencia ha aumentado en forma considerable durante las últimas décadas, favorecido por el aumento en la supervivencia y los métodos de detección más tempranos, tales como, el uso masivo del antígeno prostático específico (APE). En los EE.UU., 1 de cada 6 varones tendrá CP en algún momento de su vida, o lo que es lo mismo, el 15 por ciento. Esta patología es la más frecuente en varones (36 por ciento) y la segunda causa de muerte por cáncer (13 por ciento) luego del cáncer de pulmón. Sin embargo, pese al gran avance que se ha observado en el diagnóstico y tratamiento, la mortalidad por CP no ha disminuido, a lo que se añade que la terapia estándar para el CP estadio D2 no se ha modificado durante las últimas cinco décadas. Las opciones terapéuticas del CP localizado en el tejido prostático o localmente avanzado son: prostatectomía radical, radioterapia, braquiterapia, crioterapia o vigilancia. Eventualmente y para fines de investigación se pueden combinar éstos tratamientos. Lamentablemente la recurrencia de enfermedad (aun bioquímica) luego de la cirugía o radioterapia con intento curativo, varía entre un 27 y un 53 por ciento. Esto implica que sólo un limitado número de pacientes está curado...(AU)

Terapia hormonal sustitutiva con estradiol valerato y ciproterona acetato / Substitutive hormonal therapy with estradiol valerate and cyproterone acetate

El tratamiento del síndrome climatérico con (terapia combinada secuencial de 21 días; estradiol valerato 2 mg y ciproterona acetato 1 mg) es adecuado para el control de la sintomatología climatérica y para la prevención de osteoporosis postmenopáusica. Este preparado es tan eficaz como el resto de los preparados estrógeno-progestativos conocidos, presentando reacciones adversas similares. Sin embargo, atendiendo al perfil lipídico, tensión arterial y control del ciclo, el empleo de la ciproterona como gestágeno sí conlleva ciertas ventajas. La mayoría de las mujeres en tratamiento experimentan un aumento de las HDL- colesterol y un mantenimiento de las cifras de tensión arterial, habiéndose incluso descrito descensos estadísticamente significativos de la tensión arterial diastólica. Hasta un 87,7 por ciento de las mujeres tratadas experimenta ciclos regulares. Por tanto, este nuevo preparado hormonal puede ser considerado como un tratamiento de elección para mujeres perimenopáusicas y aquellas postmenopáusicas iniciales que acepten volver a tener menstruaciones

Changes in normal lipid profile of menopausal women with combined hormone replacement therapy. Comparative clinical trial of two hormonal combinations (conjugated estrogens/medroxyprogesterone acetate versus estradiol valerate/cyproterone acetate).

OBJECTIVES: To compare the effect on plasma lipids of conjugated estrogens/medroxyprogesterone acetate (CE/MPA) and estradiol valerate/cyproterone acetate (EV/CPA) in healthy peri and postmenopausal women during 1 year. METHODS: Multicentric, controlled, single blinded Phase III clinical trial. Women were randomized to two treatment groups: Group A (n = 49 women): CE 0.625 mg/day for 21 days and MPA 5 mg from day 12 to 21. Group B (n = 55 women): EV 2 mg/day for 21 days and CPA 1 mg from day 12 to 21. Total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C), triglycerides, aminotransferases and alkaline phosphatase were measured before starting therapy, and after 3, 6, 9 and 12 months of hormone replacement therapy (HRT). TC/HDL-C and LDL-C/HDL-C ratios were determined. RESULTS: There were no changes in TC levels. HDL-C increased and LDL-C decreased significantly, with no differences between groups but within each group. Triglycerides increased significantly but remained within normal values, with no differences between groups. TC/HDL-C ratio showed a slight and steady decrease in both groups. LDL-C/HDL-C ratio decreased in both treatment groups. CONCLUSION: Both cyclic sequential preparations used in HRT showed a favorable effect on plasma lipids in healthy peri and postmenopausal women, with an increase in HDL-C and a decrease in LDL-C levels, as well as in the LDL-C/HDL-C and TC/HDL-C ratios. Our study confirms the positive effect of estrogens on lipids, which does not seem to be adversely affected by the addition of progestogens derived from pregnanes.

Androgen regulation of glycosidase secretion in epithelial cell cultures from human epididymis.

The human epididymis and its secretions actively promote sperm fertilizing capacity and provide protection for spermatozoa against harmful influences. Among epididymal secretions, glycosidases have been recently studied and associated with molecular changes on the sperm surface. In the present work, we studied the influence of different concentrations of testosterone, dihydrotestosterone and cyproterone acetate on the secretion of alpha-glucosidase, N-acetyl-glucosaminidase, beta-glucuronidase and alpha-mannosidase by isolated and cultured epithelial cells from human caput, corpus and cauda epididymides. Cell cultures were obtained from aggregates of isolated tubule fragments plated on extracellular matrix-covered multi-well plates. Activities of the glycosidases were measured in conditioned culture media and were higher in the distal regions of the epididymis. Testosterone and dihydrotestosterone significantly increase the enzyme secretion in a concentration-dependent manner. This increase was higher in corpus and/or cauda than in caput epididymis. Cyproterone acetate caused a dose-dependent decrease in glycosidase secretion in cultures from all epididymal regions. It is concluded that the secretion of epididymal glycosidases is regulated by androgen, being stimulated by dihydrotestosterone and testosterone and inhibited by the androgen antagonist cyproterone acetate.

Chronopharmacokinetic behaviour of cyproterone acetate in rabbits.

Cyproterone acetate (CPA) is an antiandrogenic compound that shows a rhythmic toxicologic behaviour. The purpose of this study was to determine whether CPA pharmacokinetics in the rabbit were influenced by the administration time of day. Previously synchronised rabbits received a single intravenous dose of 4 mg kg(-1) of CPA at two hours after light onset (2 HALO) and 14 hours (14 HALO) after light onset. The drug concentration in plasma samples was determined by high performance liquid chromatography. The mean concentrations in plasma were significantly higher (P<0.05) in 2 HALO than in 14 HALO animals at five, 15 and 30 minutes after dosing. Both plasma concentration profiles were fitted to two-compartment open models. Mean A, Vc and Vss differed significantly between 2 and 14 HALO dosage (P<0.005). Temporal variations in plasma protein binding, drug distribution and in drug elimination may play an important role in explaining these results.

Hirsutismo / Hirsutism

El hirsutismo representa para el médico una posible enfermedad sistemática, sin embargo para la paciente connotaciones emocionales. De una buena comprensión fisiopatológica del problema, resultará un buen diagnóstico y un manejo racional de este importante problema. Se realiza una actualización del tema, enfatizando el rol de la piel como órgano blanco de la acción hormonal

Tratamento do hirsutismo com acetato de ciproterona e estrógenos conjugados em esquema sequencial reverso / Treatment of hirsutism with cyproterone acetate and conjugate estrogens by the reverse sequencial cheme

Os autores trataram 37 mulheres hirsutas com acetato de ciproterona e estrógenos conjugados em esquema sequencial reverso. Os resultados cosméticos foram excelentes e houve diminuiçäo dos níveis plasmáticos de Testosterona, DHEAS e 17 -OHP evaliados por radioimunoensaio