Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study) |
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Authors: | Jones T Hugh,Arver Stefan,Behre Hermann M,Buvat Jacques,Meuleman Eric,Moncada Ignacio,Morales Antonio Martin,Volterrani Maurizio,Yellowlees Ann,Howell Julian D,Channer Kevin S TIMES Investigators |
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Affiliation: | The Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital, Barnsley, UK. hugh.jones@nhs.net |
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Abstract: | OBJECTIVEThis 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).RESEARCH DESIGN AND METHODSThe 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).RESULTSTRT 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 (HbA1c: 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.CONCLUSIONSOver 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.Low serum testosterone is common in men with type 2 diabetes and/or metabolic syndrome (MetS) and numerous studies have reported an association between testosterone deficiency and visceral obesity, insulin resistance (IR) and dyslipidemia (1–4). In men with type 2 diabetes, low testosterone is associated with a high prevalence of symptomatic hypogonadism (3), frequently due to hypogonadotrophic hypogonadism (5).Small studies have demonstrated that testosterone replacement therapy (TRT) in hypogonadal men with and without type 2 diabetes is associated with reductions in IR, waist circumference, cholesterol, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) concentrations (6–9). Conversely, withdrawal of TRT in hypogonadal men leads to decreased insulin sensitivity (10). Furthermore, androgen suppression therapy for prostate cancer can result in alterations of individual cardiovascular risk factors and increases the occurrence of incident diabetes, myocardial infarction and sudden cardiac death (11,12). Epidemiologic studies have reported that low testosterone in men is associated with increased all-cause and cardiovascular mortality (13).The TIMES2 (Testosterone replacement In hypogonadal men with either MEtabolic Syndrome or type 2 diabetes) study investigated the effects of transdermal TRT on IR, selected cardiovascular risk factors, and symptoms in hypogonadal men with MetS and/or type 2 diabetes. The safety and tolerability of a novel, metered-dose, transdermal 2% testosterone gel were also examined. |
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