Article

Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study)

The Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital, Barnsley, UK.
Diabetes care (Impact Factor: 8.42). 03/2011; 34(4):828-37. DOI: 10.2337/dc10-1233
Source: PubMed

ABSTRACT

This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).
The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0-6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6-12).
TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA(1c): treatment difference, -0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.
Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.

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    • "Regarding the cardiovascular system, low testosterone has been associated with increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as with impaired left ventricular function; however, TRT has not been proven so far to be beneficial with respect to cardiovascular disease; neither has it been definitely shown to have specific adverse cardiovascular effects [29]. Additional data from recent studies suggest a beneficial effect of TRT in special populations, such as men with testosterone deficiency and type 2 diabetes mellitus as far as survival [30], glycemic control, cholesterol concentrations, body composition, libido and sexual function [31], as well as patient-reported quality of life (QoL) [32] are concerned. According to the BLAST-study [33], achieving threshold serum concentrations seems to be of significant importance for the response to TRT. "
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    ABSTRACT: Introduction: Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. Aims: The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.
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    • "glucose and lipid metabolism and ED (Isidori et al., 2005; Corona et al., 2011; Jones et al., 2011; Hackett et al., 2013,2014), while Met, beside its universally well-known antiglycaemic role, is generally considered as a drug with weightneutral effect (Handelsman et al., 2015; Inzucchi et al., 2015), and as not having an intrinsic positive effect on the lipid profile (Wulffel e et al., 2004), it is necessary to point out that we were not able to identify each drug (T or Met) and/or lifestyle changes (or all together those factors) as predominantly having caused those clinical and metabolic improvements. However , in our experience, although that treatment regimen and serum T and its bioavailable fractions (FT and BioT) were in the normal range for adult men (Wang et al., 2008; Bhasin et al., 2010), neither clinical signs (BMI), metabolic parameter (HbA1c, TC and LDL) nor the IIEF score reached those values that were considered as appropriate targets for the treatment in young adult obese subjects affected by T2DM without severe complications (Apovian et al., 2015; Handelsman et al., 2015; Inzucchi et al., 2015; Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Cheng AY, 2013; Rosen et al., 2002) (Tables 1 and 4). "
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    No preview · Article · Oct 2015 · Andrology
    • "Other potential drivers of DM consistent with the same observation of greater vulnerability to DM at lower body mass index in Asians, such as lower muscle mass [6], which is a sink for glucose disposal, are rarely considered. Experimental evidence from randomized controlled trials shows that increasing muscle mass through exercise or through testosterone administration improves glucose metabolism [7] [8], consistent with some observational evidence [9]. Peak lifetime muscle mass is acquired in adolescence. "
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