No abstract

Objective: The relationship between metabolic syndrome (MS) and hypogonadism has always been investigated in study groups confounded with aging, obesity or chronic metabolic disorders. So far, there has been no data about the presence of MS in young hypogonadal patients. Also, there is controversial data about the metabolic effects of testosterone replacement therapy. We investigated the frequency of MS in treatment-naïve, young men with congenital hypogonadal hypogonadism (CHH). We also searched for the effect of testosterone replacement on the metabolic profiles of this specific patient group. Design: Retrospective analysis. Methods: A total of 332 patients (age 21.68G2.09 years) were enrolled. The control group included 395 age-and body mass index (BMI)-matched healthy young men (age 21.39G1.49 years). Standard regimen of testosterone esters (250 mg/3 weeks) was given to 208 patients. Results: MS was more prevalent in CHH (P!0.001) according to healthy controls. The patients had higher arterial blood pressure, waist circumference (WC), triglyceride (P!0.001 for all), fasting glucose (PZ0.02), fasting insulin (PZ0.004), homeostatic model assessment of insulin resistance (HOMA-IR) (PZ0.002) and lower high density lipoprotein (HDL) cholesterol (P!0.001) levels. After 5.63G2.6 months of testosterone treatment, the BMI, WC (P!0.001 for both), systolic blood pressure (PZ0.002) and triglyceride level (PZ0.04) were increased and the total and HDL cholesterol levels were decreased (PZ0.02 and P!0.001 respectively). Conclusions: This study shows increased prevalence of MS and unfavorable effects of testosterone replacement in young patients with CHH. Long-term follow-up studies are warranted to investigate the cardiovascular safety of testosterone treatment in this specific population.

The enzyme chitotriosidase (ChT) is secreted by activated macrophages and play active role in human immune response. ChT activity is increased in atherosclerosis in association to the extent of the disease. We investigated the relevance of ChT to endothelial functions and insulin resistance in patients with T2DM. Forty newly diagnosed and untreated patients with T2DM (male 17; age 47.0 ± 6.2 years) and 50 healthy volunteers (male 21; age 50.2 ± 8.8 years) were enrolled. Plasma asymmetric dimethyl arginine (ADMA) levels were determined by ELISA. ChT activity was measured by the fluorescence method. Insulin resistance was calculated by the HOMA-IR formula. The patients had higher systolic blood pressures, HOMA-IR, ADMA levels, and ChT activities (P < 0.001 for all) and lower HDL cholesterol levels (P = 0.03) than the control group. The ChT activities of the total group were significantly correlated to the age (r = 0.031, p = 0.003), ADMA (r = 0.22, p = 0.04), and plasma glucose levels (r = 0.27, p = 0.01). ChT was the independent determinant of the plasma ADMA levels (r = 0.26, p = 0.02). The results of this study show that serum ChT activity is increased in patients with newly diagnosed, untreated, and uncomplicated patients with T2DM. The results also imply that increased ChT activity may be a predictor of endothelial dysfunction.

Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.