Differential effects of 11 years of long-term injectable testosterone undecanoate therapy on anthropometric and metabolic parameters in hypogonadal men with normal weight, overweight and obesity in comparison with untreated controls: real-world data from a controlled registry study

Abstract

Background and significance Obesity is a chronic disease, warranting long-term medical intervention. We evaluated effects of testosterone (T) therapy (Th) in men with T deficiency with normal weight, overweight and obesity on anthropometric and metabolic parameters, compared with untreated men. Methods Hypogonadal men (n = 823) with total T ≤ 12.1 nmol/L (age: 60.6 ± 7.0 years) participated in an ongoing registry study. Among these men 474 (57.6%) were obese, 286 (34.8%) overweight and 63 (7.7%) had normal weight. T undecanoate injections were administered to 428 men and 395 remained untreated. Anthropometric and metabolic parameters were measured at least twice a year and changes adjusted for confounding factors to account for baseline differences between groups. Results Long-term TTh in hypogonadal men, irrespective of weight at baseline, produced improvements in body weight, waist circumference (WC) and body mass index (BMI). Furthermore, TTh decreased fasting blood glucose and HbA 1c and improved lipid profiles. Gradual decreases in blood pressure (systolic and diastolic) and pulse pressure occurred in men treated with T in each group. Marked reductions in mortality and major cardiovascular events were recorded in men receiving TTh. Conclusions Our findings demonstrate that TTh produces reductions in weight, WC, and BMI. There were 77 (19.5%) deaths in the untreated groups and 23 (5.4%) in the T-groups. Based on these findings we suggest that long-term TTh in overweight and obese hypogonadal men produces progressive and sustained clinically meaningful weight loss and that TTh may contribute to reductions in mortality and incident major adverse cardiovascular events.

Testosterone Therapy for Prevention and Treatment of Obesity in Men

“…52 A real-world evidence (RWE) study of men with TD and various body weight categories investigated the effect of long-term TTh for up to 11 years. 42 All men in the control group, regardless of baseline weight status, experienced a marked increase in body weight and WC. 42 Importantly, the greatest increases in body weight and WC occurred after 6 years in men with normal weight and overweight at baseline.…”

“…42 All men in the control group, regardless of baseline weight status, experienced a marked increase in body weight and WC. 42 Importantly, the greatest increases in body weight and WC occurred after 6 years in men with normal weight and overweight at baseline. As expected, T levels significantly declined over time, from 9.5 to 8.5 nmol/L in the normal weight, from 9.6 to 8.2 nmol/L in the overweight, and from 9.8 to 7.7 in the obese groups, respectively.…”

“…In men with TD, diet-associated weight loss leads to modest increases in T, 2.87 nmol/L (83 mg/dL) with 10% loss of body weight. 41 Bariatric surgery (30% loss of body weight) is associated with a more marked increase in total T of 8.73 nmol/L (252 mg/dL), 42 and it has been suggested that this may contribute to the health benefits seen in men after bariatric surgery. 41 A Mendelian randomization analysis confirmed the causal effect of BMI on serum T in men; weight loss resulting in a reduction of BMI from 30 to 25 kg/m 2 was estimated to correspond to a 13% increase in serum T. 43 Similar results were found in the prospective Massachusetts Male Aging Study (MMAS).…”

“…As expected, T levels significantly declined over time, from 9.5 to 8.5 nmol/L in the normal weight, from 9.6 to 8.2 nmol/L in the overweight, and from 9.8 to 7.7 in the obese groups, respectively. 42 This suggests that the causal role of TD in the development of obesity takes multiple years to fully manifest.…”

“…Further proof of the causal role of TD in the pathogenesis of obesity comes from a growing number of studies showing that TTh significantly reduces markers of obesity (including body weight, WC, waist-to-height ratio, and BMI), 42,[53][54][55] total body fat mass, 47,48,[56][57][58][59][60][61] and intra-abdominal fat mass. [61][62][63][64] The remaining sections in this review will summarize important studies regarding the potential use of TTh as a treatment for obesity in men with TD.…”