Testosterone Replacement Therapy: Effects on Blood Pressure in Hypogonadal Men.

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.

Cardiovascular Disease, Hypogonadism and Erectile Dysfunction: Early Detection, Prevention and the Positive Effects of Long-Term Testosterone Treatment: Prospective Observational, Real-Life Data.

PURPOSE: Erectile dysfunction (ED) is associated with testosterone deficiency and is a symptom of functional hypogonadism. A correlation between ED and cardiovascular disease (CVD) has been recognized, and ED has been proposed as an early marker of CVD. However, the relationship between ED and CVD risk in hypogonadism requires clarification and whether testosterone therapy (TTh) can be a beneficial treatment strategy, but long-term data are limited. This study investigates long-term TTh in men with hypogonadism and ED with a history of CVD. METHODS: Seventy-seven patients with a history of CVD and diagnosed with functional hypogonadism and erectile dysfunction (erectile function domain score <21 on the International Index of Erectile Function questionnaire (IIEF questions 1-5)) were enrolled and TTh effects on anthropometric and metabolic parameters investigated for a maximum duration of 12 years. All men received long-acting injections of testosterone undecanoate at 3-monthly intervals. Eight-year data were analysed. Data collection registry started in November 2004 till January 2015. RESULTS: In hypogonadal men receiving TTh, IIEF increased by 5.4 (p<0.001). Total weight loss was 23.6 ± 0.6 kg after 8 years. HbA1c had declined by an average of 2.0% (P<0.0001). Total cholesterol levels significantly declined following TTh after only 1 year (P<0.0001), and HDL increased from 1.6±0.5 at baseline to 2±0.5 mmol/L following 8 years of TTh (P<0.0001). SBP decreased from 164±14 at baseline to 133±9 mmHg, signifying a reduction of 33±1 mmHg (P<0.0001). CONCLUSION: In hypogonadal men with a history of CVD, TTh improves and preserves erectile function over prolonged periods with concurrent sustained improvements in cardiometabolic risk factors. Measuring ED and testosterone status may serve as an important male health indicator predicting subsequent CVD-related events and mortality and TTh may be an effective add-on treatment in secondary prevention of cardiovascular events in hypogonadal men with a history of CVD.

Testosterone Therapy in Men With Hypogonadism Prevents Progression From Prediabetes to Type 2 Diabetes: Eight-Year Data From a Registry Study.

OBJECTIVE: Type 2 diabetes (T2D) is a public health threat. Prediabetes represents a window of opportunity for intervention to prevent T2D. Men with T2D and prediabetes often have low testosterone. Since testosterone improves glycemic control in T2D, we investigated whether testosterone therapy (TTh) in men with hypogonadism and prediabetes prevents progression to T2D. RESEARCH DESIGN AND METHODS: Three hundred and sixteen men with prediabetes (defined as HbA1c 5.7-6.4%) and total testosterone levels ≤12.1 nmol/L combined with symptoms of hypogonadism were analyzed. Two hundred and twenty-nine men received parenteral testosterone undecanoate (T-group), and 87 men with hypogonadism served as untreated control subjects. Metabolic and anthropometric parameters were measured twice yearly for 8 years. RESULTS: HbA1c decreased by 0.39 ± 0.03% (P < 0.0001) in the T-group and increased by 0.63 ± 0.1% (P < 0.0001) in the untreated group. In the T-group, 90% achieved normal glucose regulation (HbA1c <5.7%). In the untreated group, 40.2% progressed to T2D (HbA1c >6.5%). TTh was also associated with significant improvements in fasting glucose, triglyceride:HDL ratio, triglyceride-glucose index, lipid accumulation product, total cholesterol, LDL, HDL, non-HDL, triglycerides, and Aging Males' Symptoms (AMS) scale. Significant deterioration in all these parameters was seen in the untreated group. Mortality was 7.4% in the T-group and 16.1% in the untreated group (P < 0.05). The incidence of nonfatal myocardial infarction was 0.4% in the T-group and 5.7% in the untreated group (P < 0.005). CONCLUSIONS: Long-term TTh completely prevents prediabetes progression to T2D in men with hypogonadism and improves glycemia, lipids, and AMS score. TTh holds tremendous potential for the large and growing population of men with prediabetes and hypogonadism.

Remission of type 2 diabetes in a hypogonadal man under long-term testosterone therapy.

In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM) patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes. LEARNING POINTS: Hypogonadism occurs frequently in men with T2DM.In case of pronounced abdominal fat deposition and T2DM, the male patient should be evaluated for testosterone deficiency.Untreated hypogonadism can complicate the successful treatment of patients with T2DM.Under testosterone therapy, critical laboratory values are facilitated to return back to normal ranges and even complete remission of diabetes can be achieved.