Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution

Background We sought to clarify the role of testosterone substitution in terms of insulin resistance and metabolic profile dysregulation in hypogonadism. Methods Twenty-nine male Wistar rats aged 11–12 weeks were divided in three groups: control (C, n = 10), sham operation; orchiectomy (ORX, n = 9); and orchiectomy + testosterone substitution (ORX+T, n = 10). Blood samples were obtained at day 1 (operation), after 10 days (intramuscular T injection 100 μg/100 g b.w.), 25 days (second T injection) and 40 days (sacrifice). Results Hormonal replacement significantly attenuated the negative effect of orchiectomy on insulin resistance as indicated by the successive changes in both insulin levels (1.44 ± 2.94 vs. 4.10 ± 2.47 vs. 1.78 ± 0.68 ng/mL, for D1, D10 and D40, respectively; p = 0.028 and p = 0.022, respectively) and HOMA-IR index (1.36 ± 2.75 vs. 3.68 ± 1.87 vs. 1.74 ± 0.69 ng/mL, for D1, D10 and D40, respectively; p = 0.024 and p = 0.026, respectively) in the ORX+T group. Irisin levels peaked at the 10th postoperative day and were decreased at the end of the experiment (0.27 ± 0.11 vs. 0.85 ± 0.54 vs. 0.02 ± 0.07 ng/mL for D1, D10 and D40, respectively; p = 0.028 in both cases), whereas resistin levels did not differ. Experimental hypogonadism results in an unfavorable lipid profile and insulin resistance, which is not observed when the ORX animals are substituted for T.

Diagnosis and treatment of testosterone deficiency in type 2 di abetes mellitus

The purpose — to optimize approaches to the diagnosis and treatment of testosterone deficiency in men with type 2 diabetes mellitus. Materials and methods. We examined 147 men with type 2 diabetes at the age from 28 to 75 years old. The definition of testosterone total (cT), free testosterone (fT), estradiol (E2), sex steroid-binding globulin (CSHG), dihydrotestosterone (DHT), prostate-specific antigen total (PSA) in serum by immune-enzymatic method was performed. Substitution therapy with testosterone preparations was carried out by us to 89 patients. Results. Our studies conducted among men with type 2 diabetes have found a decrease in the mean T blood level in patients with type 2 diabetes compared with the control. The mean levels of DHT were lowered compared to control. The average levels of E2 did not differ from those of the control. The average concentration of CSHG was reduced compared to control. On the background of testosterone therapy, stabilization of the level of total testosterone at the level of eugonadal values was observed in men who received testosterone substitution after 3 months of therapy. Conclusions. Men with diabetes type 2 need to be checked for testosterone concentration annually. In the case of a decrease in T level below 8 nmol/l it is necessary to conduct substitution therapy. In cases where T levels are within the ≪gray zone≫ of 12-8 nmol/l, additional laboratory tests are needed: the determination of free T levels, estradiol, CSHG.

Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin

Background: Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism. Case presentation: A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex. Conclusions: In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.

Resúmenes de las Conferencias Misceláneos

Listado Testosterona en pacientes con cáncer de próstata. Dr. César Augusto González Encinales Current concepts for treating male hypogonadism. Eberhard Nieschlag Testosterone substitution in the aging male: when and how? Eberhard Nieschlag Indicación para el tratamiento del hipoparatiroidismo con PTH Henry Mauricio Arenas Quintero Continuing medical education, and how to do it. Leslie De Groot Transgender medicine – diagnosis & management. Michael S. Irwig MD Tumores neuroendocrinos funcionales pancreáticos: insulinoma Diva Cristina Castro Martínez Enfoque psiquiátrico del paciente transgénero. Dra. Juana Atuesta

Peculiarities of pathogenesis, diagnostics and treatment of erectile dysfunction in patients presenting with hypogonadism

Different authors estimate the prevalence of hypogonadism and erectile dysfunction at 1.7% to 35%. The contribution of androgens playing an important role in regulation of erection remains the subject of extensive investigations. To date, experimental and clinical studies have demonstrated that androgen deficiency leads to degeneration and apoptosis of smooth muscle cells followed by fibrosis of cavernous bodies, impaired expression of endothelial and neuronal NO synthase, decreased arterial inflow and increased venous drainage of the cavernous bodies, enhanced sensitivity to mediators of vasoconstriction, impaired NO-mediated relaxation of smooth muscles in response to sexual stimulation, reduced expression of type 5 phosphodiesterase (PDE-5). Moreover, hypogonadism and erectile dysfunction are frequently associated with cardiovascular disorders, diabetes mellitus, metabolic syndrome, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity. The main purpose of hormonal substitution therapy is to maximally normalize the physiological concentration of plasma testosterone and to eliminate clinical manifestations of androgen deficiency. The treatment with testosterone-containing preparations is indicated only for patients with clinical symptoms and laboratory findings suggestive of hypogonadism. The testosterone-based preparations for intramuscular administration currently find wide application for this purpose. Testosterone substitution therapy enhances libido, increases the frequency of morning erection, and improves sexual quality of life at large. It is worthy of note that treatment with these preparations is well tolerated by the patients. Control over hormonal substitution therapy with testosterone preparations implies evaluation of the clinical response and achievement of the target testosterone level in blood plasma. Also. it is necessary to measure PSA, perform digital rectal examination, and determine the hematocrit level prior to the initiation of the treatment, 3 and 6 months after its termination, and every 6 months thereafter. To conclude, androgens are natural stimulators maintaining sexual function in men. Patients with hypogonadism and erectile dysfunction should be managed by combined therapy with androgens and PDE-5 inhibitors.