Abstract
AimTo explore the metabolic phenotype of obesity-related secondary hypogonadism (SH) in men pre-replacement and post-replacement therapy with long-acting intramuscular (IM) testosterone undecanoate (TU).MethodsA prospective observational pilot study on metabolic effects of TU IM in male obesity-related SH (hypogonadal [HG] group, n = 13), including baseline comparisons with controls (eugonadal [EG] group, n = 15). Half the subjects (n = 7 in each group) had type 2 diabetes mellitus (T2D). Baseline metabolic assessment on Human Metabolism Research Unit: fasting blood samples; BodPod (body composition), and; whole-body indirect calorimetry. The HG group was treated with TU IM therapy for 6–29 months (mean 14.8-months [SD 8.7]), and assessment at the Human Metabolism Research Unit repeated. T-test comparisons were performed between baseline and follow-up data (HG group), and between baseline data (HG and EG groups). Data reported as mean (SD).ResultsOverall, TU IM therapy resulted in a statistically significant improvement in HbA1C (9 mmol/mol, P = 0.03), with 52% improvement in HOMA%B. Improvement in glycaemic control was driven by the HG subgroup with T2D, with 18 mmol/mol [P = 0.02] improvement in HbA1C. Following TU IM therapy, there was a statistically significant reduction in fat mass (3.5 Kg, P = 0.03) and increase in lean body mass (2.9 kg, P = 0.03). Lipid profiles and energy expenditure were unchanged following TU IM therapy. Comparisons between baseline data for HG and EG groups were equivalent apart from differences in testosterone, SHBG and basal metabolic rate (BMR).ConclusionIn men with obesity-related SH (including a subgroup with T2D), TU IM therapy improved glycaemic control, beta cell function, and body composition.
Highlights
Weight-gain in men, with resultant obesity is commonly associated with the development of obesity-related secondary hypogonadism (SH) [1, 2]
In the hypogonadal (HG) group (n = 13), subjects were treated with testosterone undecanoate (TU) IM therapy (TRT) for at least 6-months between baseline and follow-up metabolic assessments at the Human Metabolism Research Unit (HMRU)
In this well-phenotyped study on the metabolic effects of testosterone undecanoate intramuscular (TU IM) therapy in obese men with secondary hypogonadism, we demonstrate significant improvements in glycaemic control and favorable changes in body composition, consistent with several other studies reported with testosterone replacement therapy (TRT) [11, 15,16,17]
Summary
Weight-gain in men, with resultant obesity is commonly associated with the development of obesity-related secondary hypogonadism (SH) [1, 2]. There are complex interlinks between the development of obesity-related SH and other metabolic dysfunctions including impaired glucose tolerance, type 2 diabetes mellitus (T2D), hypertension, dyslipidaemia, and obstructive sleep apnoea (OSA). In a further study from the Netherlands on 160 obese men, obesity-related SH (based on total testosterone levels) was present in 57.5% of the sample [4]. It should be noted, that levels of plasma testosterone are reduced spuriously by non-fasting status [5]. There is some controversy regarding the true prevalence of obesity-related SH, and future studies in this field should avoid use of non-fasting measurements of plasma testosterone levels
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