TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-toevent analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-toevent analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-toevent analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-toevent analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

TRAVERSE (TheRapy for Assessment of long-term Vascular events and Efficacy ResponSE in hypogonadal men) is multicentre randomized, double-blind, placebo-controlled, noninferiority trial of testosterone therapy, enrolling 5,246 men 45 to 80 years of age who had pre-existing or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.Subjects required two fasting testosterone levels of less than 10.4 nmol/L. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 12 nmol/L and 26 nmol/L) or placebo gel for a mean 27.1 months. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke, assessed in a time-toevent analysis. TRAVERSE found no increase in major adverse cardiac events or prostate related events, including prostate cancer, effectively addressing the concerns raised by the United States Food and Drug Administration.

A third of men with type 2 diabetes (T2DM) have hypogonadotrophic hypogonadism (HH) and associated increased risk of cardiovascular and all-cause mortality. Men with HH are at increased risk of developing incident T2DM. We conducted MEDLINE, EMBASE, and COCHRANE reviews on T2DM, HH, testosterone deficiency, cardiovascular and all-cause mortality from May 2005 to October 2017, yielding 1,714 articles, 52 clinical trials and 32 randomized controlled trials (RCT). Studies with testosterone therapy suggest significant benefits in sexual function, quality of life, glycaemic control, anaemia, bone density, fat, and lean muscle mass. Meta-analyses of RCT, rather than providing clarification, have further confused the issue by including under-powered studies of inadequate duration, multiple regimes, some discontinued, and inbuilt bias in terms of studies included or excluded from analysis.
Bias (Epidemiology) ; Bone Density ; Cardiovascular Diseases ; Diabetes Mellitus, Type 2 ; Humans ; Hypogonadism ; Male ; Mortality ; Quality of Life ; Testosterone*

Diabetes Mellitus, Type 2 ; Erectile Dysfunction ; Follow-Up Studies ; Humans ; Hypogonadism ; Intra-Abdominal Fat ; Male ; Testosterone ; Waist Circumference

Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. A multi-disciplinary panel from BSSM reviewed the available literature on TD and provide evidence-based statements for clinical practice. Evidence was derived from Medline, EMBASE and Cochrane searches on hypogonadism, testosterone therapy (T Therapy) and cardiovascular safety from May 2017 to September 2022. This revealed 1,714 articles, including 52 clinical trials and 32 placebo-controlled randomised controlled trials. A total of twenty-five statements are provided, relating to five key areas: screening, diagnosis, initiating T Therapy, benefits and risks of T Therapy, and follow-up. Seven statements are supported by level 1 evidence, eight by level 2, five by level 3, and five by level 4. Recent studies have demonstrated that low levels of testosterone in men are associated with increased risk of incident type 2 diabetes mellitus, worse outcomes in chronic kidney disease and COVID 19 infection with increased all-cause mortality, along with significant quality of life implications. These guidelines should help practitioners to effectively diagnose and manage primary and age-related TD.

Purpose: While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. Materials and Methods: Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. Results: TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. Conclusions TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

Purpose: While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. Materials and Methods: Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. Results: TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. Conclusions TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.