Assistência ginecológica aos transgênero / Gynecological care for transgenders

Transgênero (trans) é um termo que alberga toda a diversidade de gênero. A incongruência de gênero faz parte desse espectro e refere-se à pessoa cuja identidade de gênero é oposta ao sexo que lhe foi atribuído no nascimento. A terapia hormonal de afirmação de gênero, bem como a cirurgia de afirmação de gênero, é necessária para adequar o corpo ao gênero ao qual a pessoa se identifica. Os homens trans necessitam da terapia com testosterona, que visa reduzir as concentrações de estradiol e incrementar a testosterona circulante para níveis fisiológicos masculinos, resultando em masculinização. A mulher trans receberá o estradiol, associado ou não a um antiandrogênico, visando reduzir a testosterona e incrementar o estrogênio para níveis femininos, resultando em feminização. A cirurgia de afirmação de gênero é, frequentemente, requerida para completar as modificações fenotípicas para o homem e a mulher trans. O ginecologista e obstetra tem um papel crucial no provimento de cuidados a essa população. O presente artigo visa sistematizar algumas ações que o ginecologista e obstetra pode oferecer e que têm potencial para melhorar a qualidade de vida dos homens e mulheres trans. (AU)

Transgenero (trans) is an umbrella term that encompasses all gender diversity. Gender Incongruity is part of this spectrum and refers to the person whose gender identity is opposed to the sex assigned to them at birth. Gender-affirming hormone therapy as well as gender-affirming surgery are necessary to adapt the body to the gender to which the person identifies. Trans men require testosterone therapy to reduce estradiol concentrations and increase circulating testosterone to male physiological levels resulting in masculinization. Trans women will receive estradiol associated or not with an antiandrogenic to reduce testosterone and increase estrogen to female levels resulting in feminization. gender-affirming surgery is often required to complete phenotypic modifications for trans men and women. The gynecologist and obstetrician plays a crucial role in to provide care to this population. This article aims to systematize some actions that the gynecologist and obstetrician can offer to improve the quality of life of trans men and women. (AU)

Implante de testosterona para la mujer, evaluación de seguridad y efectividad en esta vía de administración / Testosterone implant for women, evaluation of safety and effectiveness in this route of administration

INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.

INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Histological analysis of rat prostate under exogenous testosterone and low dose of oral selenium administration / Histología de la próstata de ratón influenciada por testosterona y la dosis supranutricional de selenio / Histologia da próstata de rato sob influência de testosterona exógena e dose supranutricional de selênio

Objective: to verify selenium effectiveness in maintenance of prostate tissue architecture. Method: experimental study using 20 adult 90-day-old male rats divided into the following groups: TG, 05 animals that received injectable testosterone; TSG, 05 animals that received injectable testosterone and weekly doses of selenium by gavage; CG1, 05 intact animals; CG2, 05 animals that received saline injection and saline by gavage. Results: characteristic architecture was found in tissue samples from animals of CG with cubic/prismatic secretory epithelium surrounded by fibro-muscular stroma. Animals of TG showed an increase in prostatic epithelium height, increase in the number of blood vessels in stroma and presence of proliferative lesions. Proliferative lesions were also found in tissue samples from animals of TSG, besides having improve in epithelial height, as seen in TG. Conclusion: it is concluded that selenium at this concentration has no effectiveness in modulating morphology of prostatic tissue of adult rats.(AU)

Objetivo: verificar la eficacia del selenio en mantener la morfología tisular. Método: estudio experimental, utilizando 20 ratones machos adultos (5 animales/grupo), divididos en: TG, recibieron testosterona inyectable; TSG, recibieron testosterona inyectable y dosis semanales de selenio por gavado; CG1, animales intactos; CG2, recibieron solución salina inyectable y por gavado. Resultados: una arquitectura característica fue encontrada en las muestras tisulares de los animales del CG, con epitelio cúbico/prismático envuelto por estroma fibro-muscular. En los animales del TG la próstata presentó un epitelio con células más altas, un aparente aumento en el número de vasos sanguíneos estromais, además de la presencia de lesiones proliferativas. También se encontraron lesiones proliferativas en las muestras tisulares de los animales del TSG, además de presentar mayor altura del epitelio, como vistas en TG. Conclusión: se concluye así que el Selenio, en esta concentración, parece no ser eficaz en la protección contra las modificaciones promovidas por la administración de T exógena en ratas adultas.(AU)

Objetivo: verificar a eficácia do selênio na manutenção da morfologia tecidual prostática. Métodos: estudo experimental, utilizando 20 ratos machos adultos, divididos em: TG, 05 animais que receberam testosterona injetável; TSG, 05 animais que receberam testosterona injetável e doses semanais de selênio por gavagem; CG1, 05 animais intactos; CG2, com 05 animais que receberam solução salina injetável e por gavagem. Resultados: uma arquitetura característica foi encontrada nas amostras teciduais dos animais do CG, com epitélio cúbico/prismático envolvido por estroma fibro-muscular. Nos animais do TG a próstata apresentou um epitélio com células mais altas, um aparente aumento no número de vasos sanguíneos no estroma, além da presença de lesões proliferativas. Também foram encontradas lesões proliferativas nas amostras teciduais dos animais do TSG, além de apresentarem maior altura do epitélio, como vistas no TG. Conclusão: conclui-se assim, que o Selênio, nesta concentração, parece não ser eficaz na proteção contra as modificações promovidas pela administração de T exógena em ratos adultos.(AU)

Influence of the use of testosterone associated with physical training on some hematologic and physical parameters in older rats with alloxan-induced diabetes

ABSTRACT Objective This study investigated the possible blood changes in wistar rats elderly with and without treatment with anabolic steroids submitted physical training. Materials and methods Elderly rats (32) were divided into four groups: normal (N), treated normal (NT), diabetic (D) and treated diabetic (DT). They were submitted to 20 sessions of swimming with overload (5% body weight), 40 min/day for four weeks. The NT and DT groups received application of testosterone twice a week. At the end of the sessions, the animals were subjected to swimming until exhaustion and then killed for removal of blood and visceral fat. We evaluated maximum swim time, weight of visceral fat, erythrogram, leukogram, lipidogram and serum levels of glucose, lactate, aspartate aminotransferase and creatine kinase. The results were compared using one-way ANOVA followed by the post hoc Tukey test. Results In elderly diabetic rats, the use of anabolic associated with physical training in older rats resulted in improvement in erythrogram, lipidogram and physical performance for high-intensity aerobic exercise. However, it was related to changes in leukocyte count, probably associated with inflammation. Conclusion The combination of the use of testosterone with physical training, followed by maximal effort test caused changes hematological and biochemical can be associated with improvement in physiological characteristics, with increase of the swimming time and decrease of visceral fat levels, improvement in aerobic metabolism of fatty acids and glucose in normal and diabetic animals.

Sexualidad y climaterio: una mirada integral / Sexuality and climacteric: a comprehensive approach

Cuando hablamos de sexualidad humana debemos saber que estamos hablando de una compleja y cambiante interacción de factores biológicos y socioemocionales altamente influenciables por la familia, la religión y los patrones culturales. Esto se ve en los hombres y en las mujeres, especialmente en las mujeres. La sexualidad es un concepto intuitivo que cuesta definir. Según la Organización Mundial de la Salud, se define salud sexual como "un estado de bienestar físico, emocional, mental y social relacionado con la sexualidad, la cual no es solamente la ausencia de enfermedad, disfunción o incapacidad". Es una definición que tiene en cuenta varios conceptos, muy importantes todos ellos. La respuesta sexual consiste en una serie de cambios neurofisiológicos, hemodinámicos y hormonales que involucran al conjunto del organismo. Si bien es similar en ambos sexos, en las mujeres no siempre el inicio y la progresión se correlacionan en forma sistemática o lineal como en los hombres. Y de ese intrigante devenir de la respuesta sexual femenina surge la dificultad del diagnóstico de la "disfunción sexual femenina". Podríamos resumirla en "un conjunto de trastornos en los que los problemas fisiológicos o psicológicos dificultan la participación o la satisfacción en las actividades sexuales; lo cual se traduce en la incapacidad de una persona para participar en una relación sexual de la forma que le gustaría hacerlo"16. La menopausia es percibida por muchas mujeres como el fin de la sexualidad, y no solo como el fin de la vida reproductiva. Si bien es cierto que en esta etapa la actividad sexual suele declinar y puede verse afectada por una serie de factores hormonales, psicológicos y socioculturales, para la mayoría de las mujeres la sexualidad sigue siendo importante. Debemos comprender que la disfunción sexual femenina, en cualquier etapa de la vida, es multicausal y multidimensional. A la hora de realizar el abordaje de una paciente, debemos tener en cuenta todos los factores involucrados y saber con qué herramientas contamos. El abordaje terapéutico clásicamente incluye la terapia psicológica y la terapia hormonal. Sin embargo, recientemente se ha incorporado una nueva droga recientemente aprobada por la FDA de los Estados Unidos para el tratamiento del deseo sexual hipoactivo en la mujer: el flibanserín, un psicofármaco que actúa a nivel de mediadores del deseo sexual en el sistema nervioso central, favoreciéndolo. (AU)

When we talk about human sexuality, we know that we are talking about a complex and changing interaction between biological and socioemotional factors, which are highly influenced by society, family, religion and cultural norms. This can be seen in men and women especially in women. Sexuality is an intuitive concept difficult to define. According to the World Health Organization, it is defined as "A state of physical, emotional, mental and social well being related to sexuality, which is not merely the absence of disease, dysfunction or disabilityˮ. It is a definition that takes into account several concepts, all very important. Sexual response is a series of neurophysiological, hemodynamic and hormonal changes involving the whole body. While similar in both sexes, women are not always the onset and progression correlate systematically or linearly as in men. And that intriguing evolution of the female sexual response, the difficulty of diagnosis of "female sexual dysfunctionˮ. We could summarize it in "a group of disorders in which the physiological or psychological problems impede participation or satisfaction in sexual activities; which results in the inability of a person to participate in a sexual relationship the way she or he would like to do itˮ16. Menopause is perceived by many women as to the end of sexuality, not only as the end of reproductive life. Sexual activity declines with age, and may be affected by a number of hormonal, psychological and sociocultural factors, but, for most women it continues to be important. We must understand that female sexual dysfunction, at any stage of life is multicausal and multidimensional. When approaching a patient, it is important to know all the factors that are involved, and which tools we have for deal with it. Classically, the therapeutic approach has consisted of psychological therapy and hormone therapy. However, we have to consider a recently approved drug by the FDA for the treatment of hypoactive sexual desire in women: Flibanserin. It is a psychotropic substance that acts on the mediators of sexual desire on the central nervous system favoring it. (AU)

Does the use of Testosterone Enanthate as a Form of Doping in Sports Cause Early Closure of Epiphyseal in Bones? / ¿El Uso de Enantato de Testosterona como Forma de Dopaje en el Deporte Causa Cierre Epifisiario Temprano de los Huesos?

The purpose of this research is to investigate the morphometric effects of short term usage of testosterone enanthate among the anabolic androgenic steroids used as doping by athletes on humerus bones of male rats. 30 rats (35 days) were utilized in this research. The rats were divided into three equal groups. For the experimental group (n= 10), testosterone enanthate at 10 mg/kg dose in 100 µl peanut oil diluents, for the peanut oil group (n= 10), peanut oil of testosterone enanthate' diluent (100 µl) was executed intraperitoneally 5 days in a week for 3 weeks. The control group (n= 10) was nourished without any practice for 3 weeks. All rats were euthanized end of the research. Humerus bones were exposed by the dissection of rats' front extremite bones and measurements and the averages were taken. When the length of rats' humerus bones were analyzed, the growth of humerus bones of rats testosterone enanthate applied in the experimental group stopped significantly and the difference was significant (p<0.05). It was observed that among anabolic androgenic steroids, testosterone enathate's usage on male rats in puberty period caused early epiphyseal closure and stopped the growth of humerus bones significantly.

El objetivo de esta investigación fue estudiar en el húmero de ratas macho, los efectos morfométricos del uso a corto plazo de Enantato de testosterona entre los esteroides anabólicos usados como dopaje por atletas. En esta investigación se utilizaron 30 ratas divididas en tres grupos iguales. Un grupo experimental (n= 10), que se le administró Enantato de testosterona en dosis de 10 mg/kg en 100 µl diluido en aceite de maní, a otro grupo sólo se le administró aceite de maní (n= 10). La administración fue realizada por vía intraperitoneal 5 días a la semana durante 3 semanas. El grupo control (n= 10) fue alimentado durante 3 semanas. Todas las ratas fueron sacrificadas al término de la investigación. Los húmeros fueron expuestos por disección, se realizaron las mediciones y se tomaron los promedios. Cuando se analizó la longitud de los húmeros se observó que su crecimiento en las ratas del grupo experimental que recibieron Enantato de testosterona, se detuvo de manera significativa (p<0,05). Se observó que entre los esteroides anabólicos androgénicos, el uso de testosterona en ratas macho en el periodo de la pubertad causó el cierre epifisario temprano y detuvo el crecimiento del húmero de manera significativa.

Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men

PURPOSE: To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. MATERIALS AND METHODS: A total of 561 hypogonadal men from two registry studies were divided into age groups of 65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. RESULTS: Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. CONCLUSIONS: The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH.

Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder / Insuficiência adrenal leve causada por mutação do gene NR0B1 (DAX1) em menino com uma associação de hipogonadismo hipogonadotrófico, baixa estatura final e transtorno de déficit de atenção

Mutation on NROB1 (DAX1) gene can cause different phenotypes of adrenal insufficiency in infancy. Long-term evolution of these patients shows that it is possible to have an association with hypogonadotropic hypogonadism. In this article we describe the evolution of a patient with NROB1 gene mutation, diagnosed with a mild form of adrenal insufficiency, and we highlight the presence of hypogonadotropic hypogonadism and short stature, besides the presence of attention deficit disorder. Such associations should make physicians aware during the follow-up of patients with this disease.

Mutações no gene NROB1 (DAX1) podem levar a quadros de insuficiência adrenal com diferentes formas de apresentação na infância. A evolução a longo prazo desses pacientes mostra que pode haver associação com hipogonadismo hipogonadotrófico. Neste artigo, relatamos a evolução de um paciente com uma mutação do gene NROB1, diagnosticado com uma forma leve de insuficiência adrenal, na qual chamamos a atenção para a evolução com hipogonadismo hipogonadotrófico e baixa estatura final, além de apresentar transtorno de déficit de atenção. Tais associações devem ser motivo de atenção para os médicos no seguimento de pacientes portadores dessa alteração.

Reversible Infertility Associated with Testosterone Therapy for Symptomatic Hypogonadism in Infertile Couple

PURPOSE: Androgen replacement therapy has been shown to be safe and effective for most patients with testosterone deficiency. Male partners of infertile couples often report significantly poorer sexual activity and complain androgen deficiency symptoms. We report herein an adverse effect on fertility caused by misusage of androgen replacement therapy in infertile men with hypogonadal symptoms. MATERIALS AND METHODS: The study population consisted of 8 male patients referred from a local clinic for azoospermia or severe oligozoospermia between January 2008 and July 2011. After detailed evaluation at our andrology clinic, all patients were diagnosed with iatrogenic hypogonadism associated with external androgen replacement. We evaluated changes in semen parameters and serum hormone level, and fertility status. RESULTS: All patients had received multiple testosterone undecanoate (NebidoR) injections at local clinic due to androgen deficiency symptoms combined with lower serum testosterone level. The median duration of androgen replacement therapy prior to the development of azoospermia was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm concentration and serum follicle-stimulating hormone level returned to normal range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of external androgen replacement therapy in infertile men with poor sexual function can cause temporary spermatogenic dysfunction, thus aggravating infertility.

Post-partum testosterone administration partially reverses the effects of perinatal cadmium exposure on sexual behavior in rats

This study investigated the effects of perinatal cadmium exposure on sexual behavior, organ weight, and testosterone levels in adult rats. We examined whether immediate postpartum testosterone administration is able to reverse the toxic effects of the metal. Forty pregnant Wistar rats were divided into three groups: 1) control, 2) 10 mg kg-1 cadmium chloride per day, and 3) 20 mg kg-1 cadmium chloride per day. These dams were treated on gestational days 18 and 21 and from lactation 1 to 7. Immediately after birth, half of the offspring from the experimental and control groups received 50 μl (i.p.) of 0.2% testosterone. Male sexual behavior, histological analysis and weight of organs as well as serum testosterone levels were assessed. Results showed that both cadmium doses disrupted sexual behavior in male rats, and postnatal treatment with testosterone reversed the toxic effects of 10 mg kg-1 cadmium and attenuated the effects of 20 mg kg-1 cadmium. Body weight and absolute testis, epididymis, and seminal vesicle weight were decreased by the higher cadmium dose, and testosterone supplementation did not reverse these effects. Serum testosterone levels were unaffected by both cadmium doses. No histological changes were detected in all organs analyzed. Maternal cadmium exposure effects in sexual parameters of male rat offspring were explained by the altered masculinization of the hypothalamus. We suggest that cadmium damaged cerebral sexual differentiation by its actions as an endocrine disruptor and supported by the changes discretely observed from early life during sexual development to adult life, reflected by sexual behavior. Testosterone supplementation after birth reversed some crucial parameters directly related to sexual behavior.

Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism / Nova mutação no receptor do hormônio liberador de gonadotrofinas (GNRHR) em um paciente com hipogonadismo hipogonadotrófico isolado normósmico

We report a novel GNRHR mutation in a male with normosmic isolated hypogonadotropic hypogonadism (nIHH). The coding region of the GNRHR gene was amplified and sequenced. Three variants p.[Asn10Lys;Gln11Lys]; [Tyr283His] were identified in the GNRHR coding region in a male with sporadic complete nIHH. The three variants were absent in the controls (130 normal adults). Familial segregation showed that the previously described p.Asn10Lys and p.Gln11Lys are in the same allele, in compound heterozygozity with the novel variant p.Tyr283His. The p.[Asn10Lys;Gln11Lys] are known inactivating mutations. The p.Tyr283His affects a well-conserved residue, and in silico analysis suggested it is a deleterious variant. We describe a novel GNRHR mutation in a male with nIHH. Absence of the mutation in the control group, conservation among species, in silico analysis, and familial segregation suggest that p.Tyr283His, which was identified in compound heterozygozity with the p.[Asn10Lys;Gln11Lys] variants, is an inactivating mutation. Arq Bras Endocrinol Metab. 2012;56(8):540-4.

Relatamos uma nova mutação no gene GNRHR em um homem com hipogonadismo hipogonadotrófico isolado normósmico (HHIn). A região codificadora do gene GNRHR foi amplificada e sequenciada. Três variantes p.[Asn10Lys;Gln11Lys]; [Tyr283His] foram identificadas no GNRHR em um homem com HHIn esporádico. As três variantes estavam ausentes no grupo controle (130 adultos normais). A segregação familiar mostrou que as variantes previamente descritas p.[Asn10Lys;Gln11Lys] se localizavam no mesmo alelo, em heterozigose composta com a nova variante p.Tyr283His. As mutações p.[Asn10Lys;Gln11Lys] são sabidamente inativadoras. A variante p.Tyr283His afeta um resíduo bem conservado, e a análise in silico sugeriu que essa é uma mutação deletéria. Descrevemos uma mutação inédita no gene GNRHR em um paciente com HHIn nIHH. A ausência da variante no grupo controle, a conservação entre as espécies, a análise in silico e a segregação familiar sugerem que a p.Tyr283His é uma mutação inativadora, identificada em heterozigose composta com as mutações p.[Asn10Lys;Gln11Lys]. Arq Bras Endocrinol Metab. 2012;56(8):540-4.

Papel de la testosterona y el cortisol en el síndrome metabólico y la diabetes mellitus tipo 2 / Role of testosterone and cortisol in metabolic syndrome and type 2 diabetes mellitus

INTRODUCCIÓN: el síndrome metabólico y la diabetes mellitus tipo 2 son trastornos metabólicos que han sido ampliamente abordados en la literatura científica por su alta incidencia, así como la alta morbilidad y mortalidad que a ellos se asocia. En los últimos años se han explorado nuevos elementos de posible impacto en su fisiopatogenia, dentro de los que se destacan los esteroides sexuales y los glucocorticoides. En este trabajo se revisaron y comentaron los conocimientos más actuales sobre el papel de la testosterona y el cortisol en la fisiopatogenia del síndrome metabólico y de la diabetes mellitus tipo 2 en los hombres. DESARROLLO: la testosterona desempeña un papel importante en la modulación de la sensibilidad a la insulina y en la homeostasis de la glucosa, de manera que en los hombres, los niveles bajos de testosterona resultan un elemento predictor de la diabetes mellitus tipo 2 y del síndrome metabólico. Se ha establecido la existencia de una relación bidireccional y reversible entre la deficiencia de andrógenos y la adiposidad, así como entre la deficiencia de andrógenos y la resistencia a la insulina. Se sugiere que los niveles bajos de testosterona podrían predisponer a la obesidad abdominal, que provoca una alteración del metabolismo de los ácidos grasos, lo cual a la vez promovería la resistencia a la insulina. La secreción de cortisol y la de testosterona están interrelacionadas y tienen efectos inversos sobre la resistencia a la insulina. En la obesidad abdominal el eje hipotalámico-hipofisario-adrenal se hipersensibiliza lo cual provoca aumento frecuente de la secreción de cortisol y disminución de la secreción de esteroides sexuales. Por otro lado, un aumento desproporcionado de la respuesta fisiológica al estrés, induce un incremento de la secreción de cortisol que podría a su vez causar la aparición de la resistencia a la insulina y del síndrome metabólico. Uno de los mecanismos patogénicos de la resistencia a la insulina es el flujo aumentado de ácidos grasos que llega al hígado a partir del metabolismo de la grasa visceral. La relación cortisol/testosterona modula, entre otras hormonas, la acumulación de la grasa visceral; ha sido asociada, en hombres, a la mortalidad y la incidencia de enfermedades cardiovasculares isquémicas, a través de una alteración de los componentes del síndrome metabólico. Esta razón pudiera ser un indicador temprano de la resistencia a la insulina y del síndrome metabólico. Este elemento introduce una nueva dimensión dentro de la fisiopatogenia del síndrome metabólico que merece ser estudiada, con la finalidad de incrementar las potencialidades diagnósticas y terapéuticas en este campo(AU)

INTRODUCTION: metabolic syndrome and the type 2 diabetes mellitus are metabolic disorders fully approached in scientific literature due to its high incidence, as well as its association with a high morbidity and mortality. In past years new elements of potential impact in its physiopathology have been reviewed including the sexual steroids and the glucocorticoids. In present paper were reviewed and discussed the more current knowledges on the testosterone and cortisol role in the physiopathology of metabolic syndrome and type 2 diabetes mellitus in men. DEVELOPMENT: testosterone plays a significant role in modulation of sensitivity to insulin and in glucose homeostasis because of in men the low levels of testosterone are a predictor element of type 2 diabetes mellitus and of the metabolic syndrome. A bidirectional and reversible relation between androgen deficiency and the adiposity, as well as between the androgen deficiency and insulin resistance have been established. Authors suggest that low levels of testosterone could predispose to abdominal obesity provoking an alteration of fat acid metabolism, which at the same time will promote the insulin resistance. Cortisol and testosterone secretion are interrelated and have inverse effects on insulin resistance. In abdominal obesity the adrenal-hypophyseal-hypotalamic axis is hypersensitive leading to a frequent increase of cortisol secretion and a decrease of sexual steroids secretion. Besides, a disproportionate increase of stress-physiologic response induces a cortisol secretion increase which could at the same time, to provoke the insulin resistance and the metabolic syndrome. One of the pathogenic mechanisms of insulin resistance is the increased flow of fat acids arriving to liver from the visceral fat metabolism. The cortisol/testosterone relation modulates among other hormones the visceral fat accumulation has been associated in men, with mortality and with the incidence of ischemic cardiovascular diseases through an alteration of the metabolic syndrome components. This fact could be an early indicator of insulin resistance and of metabolic syndrome. This element introduces a new dimension within the metabolic syndrome physiopathology deserving be studied to increase the diagnostic and therapeutical potentials in this field(AU)

Short term testosterone replacement therapy improves libido and body composition / Reposição de testosterona a curto prazo melhora libido e composição corporal

OBJECTIVE: To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement, and controls, during six months. METHODS: We assessed, through ADAM, AMS, IIEF-5 and SF-36 questionnaires, and through clinical and laboratorial examinations, 62 patients divided into three groups: 17 hypogonadal males (HR) used intramuscular testosterone every three weeks; 14 hypogonadal males (HV) and 31 non-hypogonadal males (CV) used oral vitamins daily. RESULTS: When compared to others, HR group obtained libido improvement assessed by ADAM 1 (p = 0.004), and borderline sexual potency improvement assessed by IIEF-5 (p = 0.053), besides a decrease in waist circumference after eight weeks (p = 0.018). The remaining parameters did not differ between the groups. PSA and hematocrit remained stable in those using testosterone. CONCLUSION: Six months of testosterone replacement improved sexuality and body composition, with prostatic and hematological safety.

OBJETIVO: Avaliar a eficácia e a segurança da reposição de testosterona em homens com hipogonadismo tardio comparados a hipogonádicos sem reposição e controles, durante seis meses. MÉTODOS: Mediante os questionários ADAM, AMS, IIEF-5 e SF-36, foram feitos exame clínico e laboratorial em 62 pacientes divididos em três grupos: 17 hipogonádicos (HR) usaram testosterona intramuscular a cada três semanas; 14 hipogonádicos (HV) e 31 não hipogonádicos (CV) usaram vitaminas via oral diariamente. RESULTADOS: Comparado aos demais, o grupo HR obteve melhora da libido avaliada pelo ADAM 1 (p = 0,004) e melhora limítrofe da potência sexual avaliada pelo IIEF-5 (p = 0.053), além de diminuição da cintura a partir da oitava semana (p = 0,018). Os demais parâmetros não foram diferentes entre os grupos. PSA e hematócrito se mantiveram estáveis nos que usaram testosterona. CONCLUSÃO: A reposição de testosterona durante seis meses melhorou a sexualidade e a composição corporal, com segurança prostática e hematológica.

Effect of post-natal castration on sepsis mortality in rats

PURPOSE: To investigate the influence of castration in early periods of development on survival to experimental acute sepsis. METHODS: Four groups of 10 (ten) Wistar rats were used. The groups were comprised of males (M), females (F), males castrated on the fourth day of life (CM) and males castrated on the fourth day of life with testosterone replacement (CMR). Sepsis was induced by ligature and cecal perforation in adult life. RESULTS: The analysis of death within 24 hours following sepsis induction showed greater mortality between the M and the CMR groups as compared to the CM and F (p=0.0180) groups. Multiple correspondence analysis (MCA) indicates an association between the M and the CMR groups for death within 24 hours as well as a relationship between the F and the CM groups for the absence of death and death up to 24 hours following sepsis induction. Statistical analysis of the Kaplan-Meier survival curve through log-rank demonstrates a significant difference among the four groups (p=0.0055) and between the M and the F (p=0.0005) groups. CONCLUSION: Data suggest a better survival to sepsis within 24 hours for the F and CM groups, the presence or absence of testosterone in early periods of post-natal life being responsible for these findings.

OBJETIVO: Investigar a influência da castração em períodos precoces do desenvolvimento de ratos, na sobrevida a sepse aguda experimental quando adultos, desenvolveu-se este estudo. MÉTODOS: Utilizou-se quatro grupos de 10 ratos Wistar divididos entre machos (GM), fêmeas (GF), machos castrados no quarto dia de vida GMC) e machos castrados no quarto dia de vida com reposição de testosterona (GMCR). A sepse foi induzida por ligadura e perfuração cecal na vida adulta. RESULTADOS: A análise do óbito até 24 horas da indução da sepse mostrou maior mortalidade entre os GM e GMCR em relação aos grupos GMC e GF (p=0.0180). A análise de correspondência múltipla (ACM) indica uma associação entre si dos GM e GMCR para o óbito em 24 horas, assim como uma relação entre si dos GF e GMC para a ausência de óbito e o óbito até 24 horas. A análise estatística da curva de sobrevida de Kaplan-Meier pelo log-rank demonstra diferença significativa entre os quatro grupos (p=0,0055), e entre GM e GF (p=0,0005). CONCLUSÃO: Os dados sugerem uma maior sobrevida à sepse em 24 horas dos grupos GF e GMC, e a presença ou ausência de testosterona em períodos precoces da vida pós-natal seria responsável por este achado.

Androgens in the impotent aging males

To clarify the biological significance of age-related decline in testosterone levels and to determine the possible risks and benefits of androgen therapy in the impotent aging males. This study included 54 male patients complaining of weak erection. After thorough history taking, physical examination, two questionnaires' evaluation for quality of life and Massachusetts Male Aging Sexual Activity, the patients were treated with intramuscular injection of testosterone enanthate 250mg/three weeks for six months. Laboratory investigations, including total and free testosterone, luteinizing hormone [LH], estradiol, prostate specific antigen [PSA], complete blood picture, liver function tests and lipid profile, were done before and after treatment. Another group of 54 healthy males with matched age group and without erectile problems were taken as a control for the hormonal status. Getting erection, keeping it and sexual satisfaction were significantly improved, although no significant change was noticed in the frequency of sexual activity, full hard erection or awaken with erection after testosterone therapy as measured by Massachusetts Male Aging Study [MMAS] sexual activity questionnaire. While sexual desire and night erections were slightly improved, no changes in orgasm, vaginal penetration, general and local genital examination were observed after testosterone therapy. Physical and cognitive problems were significantly improved after testosterone therapy while affective problems did not change as measured by quality of life questionnaire. Testosterone therapy had no significant effect on red blood cells count, haemoglobin concentration, haematocrite percentage, platelet counts, serum lipid profiles and serum hepatic functions. Although no significant changes were observed in testosterone [total and free], estradiol and PSA levels, there was a significant decline in LH level after testosterone therapy. No significant difference as regards the total and free testosterone levels between the patients included and the control group. In conclusion, knowledge of the potential benefits and risks of testosterone therapy has increased dramatically, but there is still much that needs to be determined. Beneficial effects of testosterone therapy on physical problems, cognitive problems, getting erection, keeping erection and sexual satisfaction can be found. To prove or disprove that testosterone therapy will increase the risk of developing or worsening cardiovascular or prostate disease, however, will require the establishment of well-controlled large multicentric studies

Validación histológica de un posible modelo de hiperplasia nodular prostática inducido con enantato de testosterona (100mg/ml) / Histological assessment of a possible model of nodular prostatic hyperplasia induced with testosterone enantate (100 mg/ml)

Estudio preclínico realizado en la Universidad Médica de Cienfuegos, Cuba, entre junio y diciembre de 2003, con el objetivo de validar desde el punto de vista histológico un posible modelo de hiperplasia prostática. Se utilizaron 15 ratas Sprague Dawley machos de 21 días de edad. El grupo I no se castró ni recibió, tratamiento con testosterona, mientras que los grupos II y III se orquiectomizaron y se les administró testosterona (25 mg/ml) a 3mg/kg subcutánea por veintiún días y enantato de testosterona (100 mg/ml) a 14 mg/kg en dosis única, respectivamente. La observación de los cortes histológicos se realizó en diez campos de 40X. La administración de enantato de testosterona causó una disminución del número de acinos e incrementó el número de capas epiteliales celulares, las aproximaciones interglandulares, las glándulas dilatadas y la presencia de pseudopapilas; el estroma se hizo más laxo y escaso. Los cambios histológicos hiperplásicos en estos animales fueron superiores cuantitativa y cualitativamente a los producidos por la administración de testosterona durante veintiún días.