Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

SummaryObjective Men with the metabolic syndrome (MetS) have low plasma testosterone (T) levels. The aim of this study was to establish whether the normalization of plasma T improves the features of the MetS. Design A randomized, placebo-controlled, double-blinded, phase III trial of 184 men suffering from both the MetS and hypogonadism. Patients One hundred and eighty-four men, aged 35-70, with the MetS and hypogonadism (baseline total T level <12AE0 nm or calculated free T level <225 pm.), recruited in the outpatient andrology and urology clinic, Research Center for Endocrinology in Moscow, Russia. Intervention Treatment for 30 weeks with either parenteral T undecanoate (n = 113; TU; 1000 mg IM) or placebo (n = 71), administered at baseline, and after 6 and 18 weeks. One hundred and five (92AE9%) men receiving TU and 65 (91AE5%) receiving placebo completed the trial. Measurements Body weight, body mass index (BMI), waist circumference (WC), hip circumference, waist-to-hip ratio, insulin, leptin, glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein (CRP), interleukin-1-beta (IL-1b), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-a). Results There were significant decreases in weight, BMI and WC in the TU vs placebo group. Levels of leptin and insulin also decreased, but there were no changes in serum glucose or lipid profile. Of the inflammatory markers, IL-1b, TNF-a and CRP decreased, while IL-6 and IL-10 did not change significantly. Conclusions Thirty weeks of T administration normalizing plasma T in hypogonadal men with the MetS improved some components of the MetS and a number of inflammatory markers.

Introduction Low testosterone levels in men are associated with the metabolic syndrome (MetS) as well as with depressive symptoms, low vitality, and sexual dysfunction. Aim To assess the effects of testosterone administration on these subjective symptoms, which have not extensively been studied in hypogonadal men with the MetS. Main Outcome Measures The Beck Depression Inventory (BDI-IA), Aging Males’ Symptoms (AMS) scale, and International Index of Erectile Function 5-item (IIEF-5) scale at baseline, 18 and 30 weeks were analysed using multilevel analysis. Methods In a randomized, placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT00696748), 184 men suffering from both the MetS and hypogonadism were included. They were treated for 30 weeks with either parenteral testosterone undecanoate (TU; 1,000 mg IM TU, at baseline, and after 6 and 18 weeks; Nebido®) or placebo injections, 105 (92.9%) men receiving TU and 65 (91.5%) receiving placebo completed the 30-week trial. Results The 184 men were aged mean 52.1 years old (standard deviation [SD] 9.6; range 35–69), with a mean body mass index of 35.5 kg/m2 (SD 6.7; range 25.1–54.8), and a mean total testosterone level of 8.0 nmol/L (SD 4.0). There were significant improvements in BDI-IA (mean difference vs. placebo after 30 weeks: −2.5 points; 95% confidence interval [CI]: −0.9; −4.1; P = 0.003), AMS (−7.4 points; 95% CI: −4.3; −10.5; P &lt;0.001), and IIEF-5 (+3.1 points; 95% CI: +1.8; +4.4; P &lt;0.001). The effects on the BDI-IA, AMS, and IIEF-5 were strongest in men with baseline total testosterone levels &lt;7.7 mmol/L (i.e., median value). Conclusions TU administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the MetS. The beneficial effects of testosterone were most evident in men with the lowest baseline total testosterone levels.

To address widespread concerns regarding the medical condition of testosterone (T) deficiency (TD) (male hypogonadism) and its treatment with T therapy, an international expert consensus conference was convened in Prague, Czech Republic, on October 1, 2015. Experts included a broad range of medical specialties including urology, endocrinology, diabetology, internal medicine, and basic science research. A representative from the European Medicines Agency participated in a nonvoting capacity. Nine resolutions were debated, with unanimous approval: (1) TD is a well-established, clinically significant medical condition that negatively affects male sexuality, reproduction, general health, and quality of life; (2) symptoms and signs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology; (3) TD is a global public health concern; (4) T therapy for men with TD is effective, rational, and evidence based; (5) there is no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not; (6) there is no scientific basis for any age-specific recommendations against the use of T therapy in men; (7) the evidence does not support increased risks of cardiovascular events with T therapy; (8) the evidence does not support increased risk of prostate cancer with T therapy; and (9) the evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. These resolutions may be considered points of agreement by a broad range of experts based on the best available scientific evidence.

No abstract