The role of testosterone in type 2 diabetes and metabolic syndrome in men: [review] / O papel da testosterona no diabetes melito tipo 2 e síndrome metabólica em homens: [revisão]

Over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. There is evidence that hypotestosteronemia should be an element in the definition of the metabolic syndrome since low levels of testosterone are associated with or predict the development of the metabolic syndrome and of diabetes mellitus. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis. So far, studies on the effects of normalization of testosterone in hypogonadal men on glucose homeostasis are limited, but convincing, and if diabetes mellitus is viewed in the context of the metabolic syndrome, the present results of testosterone treatment are very encouraging.

Ao longo das últimas três décadas, tornou-se evidente que a testosterona desempenha um papel significativo na homeostase da glicose no metabolismo lipídico. A síndrome metabólica é um agrupamento de fatores de risco que predispõem ao diabetes melito tipo 2, aterosclerose e morbidade e mortalidade cardiovasculares. Os principais componentes da síndrome são: obesidade visceral, resistência insulínica, intolerância à glicose, hipertensão arterial e dislipidemia (triglicerídeos elevados, baixos níveis de HDL-colesterol), além de um estado pró-inflamatório e trombogênico. Estudos epidemiológicos transversais relataram uma correlação direta entre testosterona plasmática e sensibilidade à insulina, e níveis baixos de testosterona se associam com risco aumentado de diabetes tipo 2, ilustrado dramaticamente pela privação androgênica em homens com carcinoma de próstata. Baixos níveis de testosterona total e globulina transportadora de hormônios sexuais (SHBG) predizem maior incidência de síndrome metabólica. Existem agora evidências de que a hipotestosteronemia deveria ser um elemento na definição da síndrome metabólica, uma vez que baixos níveis de testosterona estão associados ou predizem o desenvolvimento de síndrome metabólica e de diabetes melito. A administração de testosterona a homens hipogonádicos reverte parte do perfil desfavorável de risco para o desenvolvimento de diabetes e aterosclerose. Até agora, os estudos relacionados aos efeitos da normalização da testosterona em homens hipogonádicos sobre a homeostase da glicose são limitados, mas convincentes e, se o diabetes melito for visto no contexto da síndrome metabólica, os resultados atuais do tratamento com testosterona são muito encorajadores.

The aging male project.

With an increasing life expectancy and a decreasing reproduction rate, the population structure changes. A Jenapharm R & D program investigates the endocrinology of aging men. In men, a decrease in production of sex steroids and other hormones with age can be observed. The typical patterns of daily rhythmicity become less distinct. This is part of a very complex picture in which not only isolated hormones are involved, but also the influence of hormones on each other. Many factors from the external and intemal environment mediated by neurotransmitters constantly affect the highly sensitive hormonal balance. Therefore, aging has also been defined as "the gradual dysfunction of homeostatic processes". Declining testosterone (T) levels are involved in 'andropausal' symptoms in men: loss of libido, erectile dysfunction, insulin receptor resistance, obesity, osteoporosis, disturbances of lipid metabolism, myocardial and circulatory disturbances, impaired well-being and mood. Data are derived from studies in hypogonadal men treated by T replacement. In such parients under T treatment libido increases, fat mass decreases, muscle strenth, bone mineral density and erythropoesis increase. Whether the symptoms of andropause in aging men could successfully be treated by T substitution remains to be investigated. Negative effects of T, especially on the prostate and the cardiovascular system, are under discussion. There is increasing evidence that low T levels seem to be a risk factor for both the prostate and the cardiovascular system. Jenapharm's new testosterone undecanoate formulation for intramuscular injection can be administered every three months. T levels remain within the physiologic range. No supraphysiologic peaks occur. In women, estrogens have beneficial non-genital effects. Studies concentrate on synthetic estrogens for men without feminizing properties such as gynecomastia and reduced testicular size. Several derivatives of 17- alpha estradiol have been synthesized some of which show selectivity for the central nervous system. CNS effects have been demonstrated in female and male animals. Cardiovascular protection by estrogens has been shown in animal and human studies. Atherosclerotic plaque size was reduced after estrogen injections in cholesterol-fed rabbits. Phytoestrogen-fed monkeys had lower total cholesterol and LDL cholesterol and higher HDL cholesterol. Apart from atherosclerotic lesions, coronary artery vascular reactivity was improved. Some of these experimental findings were confirmed in human studies in postmenopausal women with and without estrogen treatment. Whether all of the described estrogenic effects can be seen in men remains to be investigated.