Metabolic phenotype of male obesity-related secondary hypogonadism pre-replacement and post-replacement therapy with intra-muscular testosterone undecanoate therapy.

Dimitriadis GK1,2,3, Randeva HS1,2, Aftab S1,2, Ali A1, Hattersley JG2,4, Pandey S5, Grammatopoulos DK1,5, Valsamakis G1,6, Mastorakos G6, Jones TH7,8, Barber TM9,10.

Endocrine. 2018 Apr;60(1):175-184. doi: 10.1007/s12020-017-1516-x. Epub 2018 Feb 2.

1Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Clifford Bridge Road, Coventry, CV2 2DX, UK.
2Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM) and the Human Metabolism Research Unit (HMRU), UHCW NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK.
3Division of Endocrinology and Investigative Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
4School of Engineering, University of Warwick, Coventry, CV4 7AL, UK.
5Pathology Labs, UHCW NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK.
6Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieio University Hospital, Athens Medical School, 11528, Athens, Greece.
7Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Gawber Road, Barnsley, S75 2EP, UK.
8Department of Oncology and Metabolism, Univerity of Sheffield, Sheffield, S10 2RX, UK.
9Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Clifford Bridge Road, Coventry, CV2 2DX, UK. T.Barber@warwick.ac.uk.
10Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM) and the Human Metabolism Research Unit (HMRU), UHCW NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK. T.Barber@warwick.ac.uk.

Abstract
AIM: To 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).
METHODS: A 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).
RESULTS: Overall, 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).
CONCLUSION: In men with obesity-related SH (including a subgroup with T2D), TU IM therapy improved glycaemic control, beta cell function, and body composition.

KEYWORDS: Male obesity-associated secondary hypogonadism; Obesity; Secondary Hypogonadism; Testosterone; Testosterone replacement; Type 2 Diabetes Mellitus

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