Acute liver failure and liver transplantation secondary to flutamide treatment in a prostate cancer patient.

Flutamide is a first-generation nonsteroidal antiandrogen, used for treatment of advanced prostate cancer (PCa). We present the clinical case of a patient with localized high-risk PCa who started flutamide before radical prostatectomy and evolved with acute liver failure and liver transplantation. Hepatotoxicity induced by antiandrogen therapy, and current indications for first generation anti-androgen therapy were reviewed. To our knowledge, this is the first report of a man diagnosed with PCa who evolved with acute liver failure secondary to flutamide, and finally required liver transplantation.

Cambios histológicos del tracto genital y riesgo de malignidad, en hombres transgénero sometidos a tratamiento androgénico / Histological changes of the genital tract and risk of malignancy in transgender men undergoing androgenic treatment

RESUMEN Introducción y objetivos: La identidad de género es la vivencia interna e individual del género tal como cada persona la siente. En algunos casos, la adquisición de los caracteres sexuales secundarios del otro género es importante en el proceso de reasignación de género, siendo importante el tratamiento endocrinológico. La cuestión es si la administración prolongada de andrógenos es segura en los casos de pacientes transexuales mujer a hombre, ya que es poca la evidencia científica a largo plazo. El objetivo de este estudio es analizar las características clínicas de los pacientes trans de nuestra unidad, y los hallazgos anatomopatológicos de las piezas quirúrgicas de histerectomía y doble anexectomía, para ver la influencia de la androgenoterapia en los genitales internos femeninos. Métodos: Se trata de un estudio descriptivo donde se analizaron datos demográficos y clínicos de los pacientes remitidos para cirugía genital, así como se analizaron los resultados del estudio anatomopatológico de las piezas de histerectomía y anexectomía. Resultados: Se incluyeron 66 pacientes, de los que 59 se intervinieron. No se halló malignidad en ninguna de las piezas quirúrgicas, sí diversos hallazgos benignos como miomas, atrofia/proliferación endometrial, actividad folicular en ovarios u ovarios tipo síndrome de ovario poliquístico. Conclusiones: La exposición a andrógenos a largo plazo no parece producir cambios malignos en la histología uterina ni ovárica, sin embargo, a menudo lleva a cambios en la actividad y la arquitectura ovárica, apreciándose en la mayoría de los casos ovarios funcionales e incluso semejantes a los observados en mujeres con ovario poliquístico.

ABSTRACT Introduction and objectives: Gender identity is the internal and individual experience of the gender as each person feels it. In some cases, the acquisition of secondary sexual characteristics of the other gender is important in the process of gender reassignment, with endocrinological treatment being important. The question is whether prolonged administration of androgens is safe in cases of transsexual women to men, since there is little scientific evidence in the long term. The aim of this study is to analyze the clinical characteristics of trans patients in our unit, and the anatomopathological findings of the surgical pieces of hysterectomy and double adnexectomy, to see the influence of androgen therapy on the female internal genitalia. Methods: This is a descriptive study where demographic and clinical data of the patients referred for genital surgery were analyzed, as well as the results of the anatomopathological study of the hysterectomy and adnexectomy pieces were analyzed. Results: 66 patients were included, of which 59 were intervened. No malignancy was found in any of the surgical pieces, but several benign findings such as myomas, endometrial atrophy / proliferation, follicular activity in ovaries or ovaries like polycystic ovary syndrome. Conclusions: Long-term exposure to androgens does not seem to produce malignant changes in uterine or ovarian histology, however, it often leads to changes in ovarian activity and architecture, with functional ovaries being seen in most cases and even similar ones. those observed in women with polycystic ovary.

Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats.

Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis. Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups (n = 10/group): T: received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle. Animals were euthanized at 180 days old by decapitation. Blood was collected to obtain hormone and cytokines concentrations. The ventral prostate was dissected and processed for light microscope and molecular analyses. Relative ventral prostate weight and epithelial compartment were increased after TT. The number of intact and degranulated mast cells was reduced in the T group. Plasma testosterone, DHT and intraprostatic testosterone concentrations were higher in the T group. TT leads to an increase in cell proliferation and up-regulation of AR, ERß, PAR-4, and NRF2. Importantly, plasma concentration and tissue expression of IL-10 and TNF-α were higher after TT. In summary, these results indicate that TT can regulate inflammatory response, with impacts in cytokines and mast cell population, and modulates steroids receptors, important parameters for prostatic homeostasis.

Diferentes respuestas somáticas y densitométricas sobre el hueso cortical y trabecular a la androgenoterapia en varones hipogonádicos / Different somatic and densitometric responses of cortical and trabecular bone to androgen therapy in hypogonadal men

Una consecuencia clínica de la deficiencia de testosterona en el varón es el descenso de la densidad mineral ósea (DMO), asociado a mayor riesgo de fractura (con la consiguiente morbi-mortalidad en el hombre añoso), y cambios de la composición y el contenido de calcio corporal total. Para cuantificar los efectos de la androgenoterapia sobre la composición corporal y el contenido de calcio corporal, correlacionar los cambios hormonales con los densitométricos y de la composición corporal, y constatar posibles diferencias densitométricas regionales, se incluyeron 15 varones hipogonádicos. Se determinaron variables antropométricas, bioquímicas, densitométricas y de la composición corporal en condiciones basales y bajo la terapia sustitutiva. Como resultado, se logró compensar el déficit androgénico y duplicar la concentración de estradiol. El eugonadismo inducido incrementó la DMO como el contenido del calcio corporal total. Además, redujo el porcentaje de masa grasa corporal total (principalmente abdominal) y aumentó la masa muscular corporal total, con incremento de la relación masa magra/masa grasa, sin cambios del índice de masa corporal. En conclusión, nuestros resultados afirman el papel preponderante de los esteroides sexuales sobre la composición corporal y su rol en el hueso. El hipogonadismo masculino constituye un factor de riesgo para osteoporosis y enfermedad cardiovascular.

A clinical consequence of testosterone deficiency in males is the reduction of bone mineral density (BMD), associated with a higher risk of fracture (and a subsequent increase in morbi-mortality in elderly men) and with changes in body composition and total body calcium content. In order to quantify the effects of androgen therapy on body composition and body calcium content, and to correlate changes in hormone levels with densitometric changes and changes in body composition changes, as well as to determine potential regional densitometric differences, 15 hypogonadal men were included in the present study. Anthropometric, biochemical, densitometric and body composition variables were analyzed under basal conditions, and under replacement therapy. As a result, androgen deficiency was compensated, and estradiol level was twice as high. Induced eugonadism increased both BMD and total body calcium content. Also, replacement treatment reduced the percentage of total body fat, (primarily abdominal fat) and increased total muscle mass, with an increment of the lean mass/fat mass ratio, and no change in BMI. In conclusion, our results strengthen the preponderant role of sexual steroids on body composition, and its effect on bones. Male hypogonadism is a risk factor for osteoporosis and cardiovascular disease.