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Objective To determine the effect of testosterone vs placebo treatment on health-related quality of life (HR-QOL) and psychosocial function in men without pathologic hypogonadism in the context of a lifestyle intervention. Design, Setting, Participants Secondary analysis of a 2-year randomized controlled testosterone therapy trial for prevention or reversal of newly diagnosed type 2 diabetes, enrolling men ≥ 50 years at high risk for type 2 diabetes from 6 Australian centers. Interventions Injectable testosterone undecanoate or matching placebo on the background of a community-based lifestyle program. Main Outcomes Self-reported measures of HR-QOL/psychosocial function. Results Of 1007 participants randomized into the Testosterone for Type 2 Diabetes Mellitus (T4DM) trial, 648 (64%) had complete data available for all HR-QOL/psychosocial function assessments at baseline and 2 years. Over 24 months, while most measures were not different between treatment arms, testosterone treatment, compared with placebo, improved subjective social status and sense of coherence. Baseline HR-QOL/psychosocial function measures did not predict the effect of testosterone treatment on glycemic outcomes, primary endpoints of T4DM. Irrespective of treatment allocation, larger decreases in body weight were associated with improved mental quality of life, mastery, and subjective social status. Men with better baseline physical function, greater sense of coherence, and fewer depressive symptoms experienced greater associated decreases in body weight, with similar effects on waist circumference. Conclusion In this diabetes prevention trial, weight loss induced by a lifestyle intervention improved HR-QOL and psychosocial function in more domains than testosterone treatment. The magnitude of weight and waist circumference reduction were predicted by baseline physical function, depressive symptomology, and sense of coherence. [ABSTRACT FROM AUTHOR]

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious effects. The glucocorticoid receptor (GR) is the site of action for these hormones and a vast body of work has been conducted understanding its function. Traditionally, it was thought that the anti-inflammatory benefits of glucocorticoids were mediated by transrepression of pro-inflammatory transcription factors, while the adverse metabolic effects resulted from direct transactivation. This canonical understanding of the GR function has been brought into question over the past 2 decades with advances in the resolution of scientific techniques, and the discovery of multiple isoforms of the receptor present in most tissues. Here we review the structure and function of the GR, the nature of the receptor isoforms, and the contribution of the receptor to glucocorticoid sensitivity, or resistance in health and disease. [ABSTRACT FROM AUTHOR]

Context The T4DM study randomized 1007 men with impaired glucose tolerance or newly diagnosed diabetes to testosterone undecanoate (TU, 1000 mg) or matching placebo (P) injections every 12 weeks for 24 months with a lifestyle program with testosterone (T) treatment reducing diabetes diagnosis by 40%. Background The long-term effects on new diagnosis of diabetes, cardiovascular and prostate disease, sleep apnea, weight maintenance trajectory and androgen dependence were not yet described. Methods A follow-up email survey after a median of 5.1 years since last injection obtained 599 (59%) completed surveys (316 T, 283 P), with participants in the follow-up survey compared with nonparticipants in 23 anthropometric and demographic variables. Results Randomization to was TU associated with stronger belief in study benefits during (64% vs 49%, P <.001) but not after the study (44% vs 40%, P =.07); there is high interest in future studies. At T4DM entry, 25% had sleep apnea with a new diagnosis more frequent on TU (3.0% vs 0.4%, P =.03) during, but not after, the study. Poststudy, resuming prescribed T treatment was more frequent among TU-treated men (6% vs 2.8%, P =.03). Five years after cessation of TU treatment there was no difference in self-reported rates of new diagnosis of diabetes, and prostate or cardiovascular disease, nor change in weight maintenance or weight loss behaviors. Conclusion We conclude that randomized T treatment for 24 months in men with impaired glucose tolerance or new diabetes but without pathological hypogonadism was associated with higher levels of self-reported benefits and diagnosis of sleep apnea during, but not after, the study as well as more frequent prescribed poststudy T treatment consistent with androgen dependence in some men receiving prolonged injectable TU. [ABSTRACT FROM AUTHOR]