Hypogonadism represents one of the most important causes of male osteoporosis. Testosterone regulates male bone metabolism both indirectly by aromatization to estrogens and directly through the androgen receptor (AR) on osteoblasts, promoting periosteal bone formation during puberty and reducing bone resorption during adult life. Early onset of testosterone deficiency, as observed in Klinefelter's syndrome (KS), is an important risk factor for precocious osteoporosis. Osteoporosis is present in up to 40% of subjects with KS and has usually been attributed to low testosterone levels. However, reduced bone mass might be present also in KS men with normal testosterone levels and testosterone replacement therapy does not always restore bone density in KS patients. Possible new determinants for osteoporosis in KS might be related to the AR function and insulin-like factor 3 (INSL3) levels. The CAG length and inactivation pattern of the AR in KS have been related to osteoporosis, but definitive proof is lacking. INSL3 has an anabolic role on bone metabolism by acting on osteoblasts and INSL3 levels are low in KS. Therefore, low INSL3 concentrations might represent a possible new pathogenic mechanism for reduced bone mass in KS.

Testosterone levels and AR CAG polymorphism are not associated with bone mass phenotype in KS.

Introduction A precise characterization of erectile dysfunction (ED) of vascular origin has not yet been achieved. Although cavernous peak systolic velocity (PSV) is generally considered a major parameter, it has many false positives and negatives because of anatomic variations of the cavernous artery course, challenging site of sampling, insufficient caracterization of an early phase of vascular disease, and significant influence of adrenergic tone. Aim We performed a high magnification ultrasonographic study in order to compare functional and morphological parameters of the cavernous artery to PSV and their relation with penile and systemic atherosclerosis. Methods A total of 109 subjects (84 ED patients and 25 controls) evaluated in our andrological center from March 2007 to January 2008 were enrolled in the study. Main Outcome Measures All subjects underwent medical history, erectile function domain of the International Index of Erectile Function, physical examination, routine and sex hormone blood tests, and high resolution echo color doppler evaluation of carotid, femoral and penile districts (acceleration time, intima media thickness [IMT], intima adventitia thickness, caliper before and after intracavernous alprostadil injection [Δ-cavernous calliper]). Results Cavernous parameters were significantly different between ED and controls. Multivariate model showed that IMT was the only predicting parameter for ED of vascular origin. Cavernous IMT showed a strong direct correlation with carotid and femoral IMT. ED patients with two or more cardiovascular risk factors had a significantly higher cavernous IMT. Conclusions An increased cavernous IMT (≥0.3 mm) might predict ED of vascular origin with more accuracy than PSV and could be a sensitive predictor also for systemic atherosclerosis at an earlier phase.

Liver is deeply involved in the metabolism of proteins, hormones, enzymes, cytokines, as well as in sex hormones catabolism. Gonadal function requires a normal liver function, and it is well known that clinical signs of hypogonadism are common in patients with liver cirrhosis. Few studies have focused on hypothalamic- pituitary-gonadal alterations in male cirrhotic patients or after orthotopic liver transplantation (OLT). The pathogenesis of hypogonadism in cirrhotic patients is complex and not well explained. It involves both a gonadal and a hypothalamic- pituitary dysfunction. After OLT the hypothalamic-pituitary-gonadal function partially improves, showing that the hepatic dysfunction before OLT is deeply involved in its pathogenesis. After OLT some alterations persist in some patients, both because of pre-existing gonadal alterations (toxic-metabolic damage) and immunosuppressive pharmacological side effects. Further studies will explain the relationship between hypogonadism and OLT outcome, and the role of androgen therapy in hypogonadism after OLT, in the early months and in the long term.

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