Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial

Abstract

BackgroundWhether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass.MethodsWe conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m2) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47–60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography).ResultsA total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of –2.9 kg (–5.7 to –0.2; P = 0.04), and in visceral fat (MAD –2678 mm2; –5180 to –176; P = 0.04). Although both groups lost the same lean mass following VLED (cases –3.9 kg (–5.3 to –2.6); controls –4.8 kg (–6.2 to –3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during weight maintenance, in contrast to controls (0.8 kg (–0.7 to 2.3), P = 0.29) so that, at study end, cases had an attenuated reduction in lean mass compared to controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002).ConclusionsWhile dieting men receiving placebo lost both fat and lean mass, the weight loss with testosterone treatment was almost exclusively due to loss of body fat.Trial registrationclinicaltrials.gov, identifier NCT01616732, registration date: June 8, 2012Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0700-9) contains supplementary material, which is available to authorized users.

The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment

“…Briefly, 100 obese (body mass index [BMI] >30 kg/m 2 ) men with a repeated fasting morning total testosterone level of <12 nmol/L confirmed by liquid chromatography/mass spectrometry were 1:1 randomized to 1000 mg intramuscular testosterone undecanoate treatment or matching placebo, administered for 56 weeks according to standard schedule. In addition, all subjects received a very low energy diet for 10 weeks followed by a 46‐week weight maintenance diet . At the 56‐week final study visit of the RCT phase, while both study investigators and participants remained blinded to treatment allocation, all men were encouraged to continue with dieting and exercise and were invited to attend for a single follow‐up appointment at the Austin Hospital Andrology Research Unit after at least 12 months following completion of the RCT for assessment of body composition and hormonal studies.…”

“…All follow‐up measurements were conducted at the study centre with the same methodology used during the RCT phase of the study. Briefly, levels of haemoglobin, haematocrit, prostate‐specific antigen (PSA), luteinizing hormone (LH), sex hormone binding globulin and total testosterone were determined by electrochemiluminescence immunoassay and free testosterone calculated as described previously . Body composition was quantified by dual‐energy absorptiometry ( prodigy , version 13.60; GE Lunar, Madison, WI, USA) …”

“…As expected, men receiving placebo lost both fat mass and lean mass during diet. In contrast, testosterone treatment prevented the diet‐associated loss of lean mass, and the weight loss among testosterone‐treated men was almost exclusively due to loss of fat mass …”

“…In addition, it is not well established whether cessation of physiologically dosed testosterone treatment is associated with long‐term iatrogenic suppression of the hypothalamic‐pituitary‐testicular (HPT) axis, which could potentially be harmful. We therefore conducted an observational follow‐up study of a recently completed RCT to investigate whether the effects of testosterone treatment on body composition in obese men were sustained after at least 12 months of treatment cessation. We also evaluated whether testosterone treatment is associated with prolonged iatrogenic suppression of the HPT axis, and whether potentially adverse effects of testosterone treatment are maintained.…”

Relationship Between Changes in Fat and Lean Depots Following Weight Loss and Changes in Cardiovascular Disease Risk Markers

“…A trial using testosterone supplementation after a very low calorie diet–induced weight loss in obese middle‐aged men produced a difference in fat‐free mass of 3.4 kg compared with placebo at the end of 12 months, but no differences were seen in blood pressure, homeostatic model assessment of insulin resistance, HDL cholesterol, or TG 28. In our study, loss of lean mass did not adversely influence the beneficial effects of weight loss, and changes in lean mass were positively related to changes in CVD risk factors.…”