up to 40% of men with T2DM have testosterone deficiency
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Acute and short term chronic testost... [J Clin Endocrinol Metab. 2014] - PubMed - NCBI - 0 views
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Study finds that Testosterone regulates glucose metabolism, in part, through adiponectin production. Early state of low T will slow the use of fats as a source of fuel and this results in an increased energy balance and results in the increased adiponectin production to increase metabolism. Testosterone and adiponectin exist in an inverse relationship. This study does not mimic normal physiology. Men with low T are unhealthy with significant metabolic dysfunction. These young, "healthy" men were induced to a low T state--that is not a clear picture as the physiology of a "young healthy" man is quite different than that of one with low T. Testosterone conversion to DHT increases GLUT4 and thus glucose uptake--another mechanism of Testosterone's effect on glucose metabolism.
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shared by Nathan Goodyear on 17 Jan 14
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Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 di... - 0 views
www.ajandrology.com/article.asp
Testosterone therapy diabetes lipids glucose triglycerides men male hormone hormones
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Among diabetic patients, a reduction in sex hormone binding globulin levels induced by insulin resistance leads to a further decline of testosterone levels
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low bioavailable testosterone concentration was related to decreased lean body mass and muscle strength
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Testosterone deficiency has a high prevalence in men with T2DM, and it is also associated with impaired insulin sensitivity, increased percentage body fat, central obesity, dyslipidemia, hypertension and cardiovascular diseases (CVD)
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A meta-analysis of four randomized controlled trials (RCTs) showed that TRT seemed to improve glycemic control as well as fat mass in T2DM subjects with low testosterone levels and sexual dysfunction.
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Insulin stimulates glucose uptake into muscle and adipose tissue via the Glut4 glucose transporter isoform. When insulin activates signaling via the insulin receptor, Glut4 interacts with insulin receptor substrate 1 to initialize intracellular signaling and facilitate glucose transportation into the cell
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The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway
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Insulin resistance as assessed by, which is calculated from the equation (If*Gf/22.5, where If is fasting insulin and Gf is fasting glucose), was definitely improved by TRT after testosterone administration in three studies
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Testosterone was observed to elevate the expression levels and stimulate translocation of Glut4 in cultured skeletal muscle cells and to upregulate Glut4 by activating insulin receptor signaling pathways in neonatal rats
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These effects were inhibited by a dihydrotestosterone (DHT) blocker, indicating that glucose uptake may correlate with conversion of testosterone to DHT and activation of the androgen receptor.
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TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men
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Epidemiological studies have found a negative relationship between testosterone levels and typical cardiovascular risk markers, such as body mass index, waist circumference, visceral adiposity and carotid intima-media thickness.
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Testosterone treatment was shown to raise hemoglobin, hematocrit and thromboxane, all of which might give rise to CVD
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Low Testosterone is a very significant problem in men with type II Diabetes. Estimated to reach 40%, likely much higher. They based these estimates only on T levels and sexual symptoms. Testosterone improves glycemic control primarily through Increased transcription and transloction of GLUT4 insulin receptors to the cell surface. Inflammation reduction is also a mechanism. Testosteorne lowers Triglycerides in the traditional lipid profile. Studies are mixed on the other aspects of lipids.
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Testosterone and glucose metabolism in men: current concepts and controversies - 0 views
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Only 5% of men with type 2 diabetes have elevated LH levels (Dhindsa et al. 2004, 2011). This is consistent with recent findings that the inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
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Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion
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Consistent with the hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
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Interestingly, a recent 16-week study of experimentally induced hypogonadism in healthy men with graded testosterone add-back either with or without concomitant aromatase inhibitor treatment has in fact suggested that low oestradiol (but not low testosterone) may be responsible for the hypogonadism-associated increase in total body and intra-abdominal fat mass
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A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
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Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
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This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
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The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
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Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
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Several observational and randomised studies reviewed in Grossmann (2011) have shown that weight loss, whether by diet or surgery, leads to substantial increases in testosterone, especially in morbidly obese men
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This suggests that weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
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There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
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successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
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weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
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In part, the discrepant results may be due to the fact men in the Vigen cohort (Vigen et al. 2013) had a higher burden of comorbidities. Given that one (Basaria et al. 2010), but not all (Srinivas-Shankar et al. 2010), RCTs in men with a similarly high burden of comorbidities reported an increase in cardiovascular events in men randomised to testosterone treatment (see section on Testosterone therapy: potential risks below) (Basaria et al. 2010), testosterone should be used with caution in frail men with multiple comorbidities
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The retrospective, non-randomised and non-blinded design of these studies (Shores et al. 2012, Muraleedharan et al. 2013, Vigen et al. 2013) leaves open the possibility for residual confounding and multiple other sources of bias. These have been elegantly summarised by Wu (2012).
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Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
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This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
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it is conceivable that testosterone treatment may have more significant effects on glucose metabolism in uncontrolled diabetes, akin to what has generally been shown for conventional anti-diabetic medications.
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the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
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Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
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the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
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testosterone is inversely associated with total cholesterol, LDL cholesterol and triglyceride (Tg) levels, but positively associated with HDL cholesterol levels, even if adjusted for confounders
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Although observational studies show a consistent association of low testosterone with adverse lipid profiles, whether testosterone therapy exerts beneficial effects on lipid profiles is less clear
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Whereas testosterone-induced decreases in total cholesterol, LDL cholesterol and Lpa are expected to reduce cardiovascular risk, testosterone also decreases the levels of the cardio-protective HDL cholesterol. Therefore, the net effect of testosterone therapy on cardiovascular risk remains uncertain.
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data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
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compared with otherwise healthy young men with organic androgen deficiency, there may be increased risks in older, obese men because of comorbidities and of decreased testosterone clearance
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shared by Nathan Goodyear on 28 Apr 15
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Diet-induced obesity and low testosterone increase neuroinflammation and impair neural ... - 0 views
www.ncbi.nlm.nih.gov/...PMC4190446
Testosterone neuroinflammation glia insulin resistance obesity diabetes brain CNS PNS inflammation low T low Testosterone TNF-alpha IL-1beta
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both obesity and low testosterone are also risk factors for neural dysfunction, including cognitive impairment [58–61] and development of AD
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diet-induced obesity causes significant metabolic disturbances and impairs central and peripheral nervous systems.
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both obesity and low testosterone are linked with promotion of inflammatory pathways [70–72] and exert harmful actions on the central [73–75] and peripheral [29,76] nervous systems
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In general, obesity-related changes were worsened by low testosterone and improved by testosterone treatment; however, this relationship was not statistically significant in several instances. Further, our data suggest that a common pathway that may contribute to obesity and testosterone effects is regulation of inflammation
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fasting blood glucose levels were independently and additively increased by GDX-induced testosterone depletion and high-fat diet
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testosterone treatment significantly reduced fasting glucose under both the normal and high-fat diets, demonstrating potential therapeutic efficacy of testosterone supplementation
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fasting insulin, insulin resistance (HOMA index), and glucose tolerance, low testosterone tended to exacerbate and or testosterone treatment improved outcomes.
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testosterone’s effects likely do not indicate an indirect result on adiposity but rather regulatory action(s) on other aspects of metabolic homeostasis
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Prior work in rodents has shown diet-induced obesity induces insulin resistance in rat brain [63] and that testosterone replacement improves insulin sensitivity in obese rats [64]. Our findings are consistent with the human literature, which indicates that (i) testosterone levels are inversely correlated to insulin resistance and T2D in healthy [30,65] as well as obese men [66], and (ii) androgen therapy can improve some metabolic measures in overweight men with low testosterone
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it has been shown that TNFα has inhibitory effects on neuron survival, differentiation, and neurite outgrowth
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Our data demonstrate that low testosterone and obesity independently increased cerebrocortical mRNA levels of both TNFα and IL-1β
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many beneficial effects of testosterone, including inhibition of proinflammatory cytokine expression
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neuroprotection [80,81], are dependent upon androgen receptors, the observed effects of testosterone in this study may involve androgen receptor activation
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testosterone can be converted by the enzyme aromatase into estradiol, which is also known to exert anti-inflammatory [82] and neuroprotective [83] actions
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Since testosterone can affect glial function [86] and improve neuronal growth and survival [87–89], it was unexpected that testosterone status exhibited rather modest effects on neural health indices with the only significant response being an increase in survival in the testosterone-treated, high-fat diet group
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testosterone treatment significantly lowered TNFα and IL-1β expression to near basal levels even in obese mice, indicating a protective benefit of testosterone across diet conditions
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Testosterone status and diet-induced obesity were associated with significant regulation of macrophage infiltration
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a possible mechanism by which obesity and testosterone levels may affect the health of both CNS and PNS
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Study points to obesity and low Testosterone contribution of neuroinflammation. No effect of body weight was seen with TRT. This animal model found similar positive effects of TRT in insulin sensitivity. Obesity and low T increase inflammatory cytokine production: this study found an increase in TNF-alpha and IL-1beta and TRT reduced TNF-alpha and IL-1beta to near base-line. Testosterone is neuroprotective and this study reviewed the small volume of evaded that pointed to benefit from estradiol. Testosterone's effect on glial survival was positive but not significant. Obesity and low T were found to be associated with increased macrophage infiltration in the PNS with increased TNF-alpha and IL-1beta. Testosterone therapy improved peripheral neuropathy via its positive effects on nocicieption.
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shared by Nathan Goodyear on 04 Feb 14
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Testosterone and glucose metabolism in men: current concepts and controversies - 0 views
joe.endocrinology-journals.org/...R37.full
Low T Testosterone metabolic syndrome MetS Diabetes men male glucose hormone hormones g
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Around 50% of ageing, obese men presenting to the diabetes clinic have lowered testosterone levels relative to reference ranges based on healthy young men
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The absence of high-level evidence in this area is illustrated by the Endocrine Society testosterone therapy in men with androgen deficiency clinical practice guidelines (Bhasin et al. 2010), which are appropriate for, but not specific to men with metabolic disorders. All 32 recommendations made in these guidelines are based on either very low or low quality evidence.
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A key concept relates to making a distinction between replacement and pharmacological testosterone therapy
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Findings similar to type 2 diabetes were reported for men with the metabolic syndrome, which were associated with reductions in total testosterone of −2.2 nmol/l (95% CI −2.41 to 1.94) and in free testosterone
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Cross-sectional studies uniformly show that 30–50% of men with type 2 diabetes have lowered circulating testosterone levels, relative to references based on healthy young men
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In a recent cross-sectional study of 240 middle-aged men (mean age 54 years) with either type 2 diabetes, type 1 diabetes or without diabetes (Ng Tang Fui et al. 2013b), increasing BMI and age were dominant drivers of low total and free testosterone respectively.
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both diabetes and the metabolic syndrome are associated with a modest reduction in testosterone, in magnitude comparable with the effect of 10 years of ageing
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In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone with anaemia
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In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
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It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker, co-existing because of in-common risk factors.
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In prospective studies, reviewed in detail elsewhere (Grossmann et al. 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone compared with total testosterone
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In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident metabolic syndrome
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low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
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In cross-sectional studies of men with (Grossmann et al. 2008) and without (Bonnet et al. 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control
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SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids
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In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
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Low free testosterone remains inversely associated with insulin resistance, independent of SHBG (Grossmann et al. 2008). This suggests that the low testosterone–dysglycaemia association is not solely a consequence of low SHBG.
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Experimental evidence reviewed below suggests that visceral adipose tissue is an important intermediate (rather than a confounder) in the inverse association of testosterone with insulin resistance and metabolic disorders.
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testosterone promotes the commitment of pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
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testosterone regulates the metabolic functions of mature adipocytes (Xu et al. 1991, Marin et al. 1995) and myocytes (Pitteloud et al. 2005) in ways that reduce insulin resistance.
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Pre-clinical evidence (reviewed in Rao et al. (2013)) suggests that at the cellular level, testosterone may improve glucose metabolism by modulating the expression of the glucose-transported Glut4 and the insulin receptor, as well as by regulating key enzymes involved in glycolysis.
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More recently testosterone has been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
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Interestingly, a reciprocal feedback also appears to exist, given that not only chronic (Cameron et al. 1990, Allan 2013) but also, as shown more recently (Iranmanesh et al. 2012, Caronia et al. 2013), acute hyperglycaemia can lower testosterone levels.
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In men with prostate cancer commencing androgen deprivation therapy, both total as well as, although not in all studies (Smith 2004), visceral fat mass increases (Hamilton et al. 2011) within 3 months
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More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several large observational registry studies
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Testosterone has also been shown to reduce the concentration of pro-inflammatory cytokines in some, but not all studies, reviewed recently in Kelly & Jones (2013). It is not know whether this effect is independent of testosterone-induced changes in body composition.
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the observations discussed in this section suggest that it is the decrease in testosterone that causes insulin resistance and diabetes. One important caveat remains: the strongest evidence that low testosterone is the cause rather than consequence of insulin resistance comes from men with prostate cancer (Grossmann & Zajac 2011a) or biochemical castration, and from mice lacking the androgen receptor.
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Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the age-related decline in testosterone levels
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there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in testosterone
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increased visceral fat is an important component in the association of low testosterone and insulin resistance
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The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone levels
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men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat mass is already present before puberty
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inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
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Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion from GNRH neurons situated in the preoptic area
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hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
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A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
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Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
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Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone levels than age alone
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55% of symptomatic androgen deficiency reverted to a normal testosterone or an asymptomatic state after 8-year follow-up, suggesting that androgen deficiency is not a stable state
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The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
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Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
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weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
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There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
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in men who improved their glycaemic control over time, testosterone levels increased. By contrast, in those men in whom glycaemic control worsened, testosterone decreased
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testosterone levels should be measured after successful weight loss to identify men with an insufficient rise in their testosterone levels. Such men may have HPT axis pathology unrelated to their obesity, which will require appropriate evaluation and management.
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shared by Nathan Goodyear on 19 May 14
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Testosterone restores insulin sensitivity in patients with diabetes and hypogonadism | ... - 0 views
www.healio.com/...with-diabetes-and-hypogonadism
testosterone insulin sensitivity diabetes resistance low T hypogonadotrophic hypogonadism GLUT4 DHT fat mass lean muscle inflammation men male hormone hormones
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This is the abstract from oral presentation at AACE in Las Vegas from May. Small study finds reduction in fat mass, increase in muscle mass, increase in insulin sensitivity, and reduction in inflammation signaling with Testosterone therapy in men with low Testosterone. These men were type 2 diabetics. This is consistent with prior published literature. However, men without diabetes, this association is hard to reproduce. The degree of glucose control also effects the response to Testosterone therapy i.e. the worse the glucose control, the more the response from Testosterone. Also of note, those men with hypogonatrophic hypogonadism had decreased insulin receptor expression, decreased insulin sensitivity, and decreased GLUT-4 expression versus eugonadal men. Remember from prior studies, it is the conversion of Testosterone to DHT that increases GLUT-4 transcription, translocation, and expression.
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shared by Nathan Goodyear on 29 Jul 14
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Effect of Testosterone Treatment on Glucose Metabolism in Men With Type 2 Diabetes: A R... - 0 views
care.diabetesjournals.org/...2098.abstract
Testosterone treatment low subcutaneous fat visceral fat T glucose insulin resistance metabolism obesity diabetes men male hormone hormones
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Only the abstract available in this publication. Good study design. No improvement in insulin resistance, glycemic control or visceral adiposity in obese men with type II diabetes. The levels of inclusion were TT < 346, which would not meet the criteria put forth by other studies. This study appeared to look at border line "low T" men with obesity and type II diabetes and found no direct glycemic control improvement. An increase in lean muscle mass and decrease in subcutaneous fat was found.
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shared by Nathan Goodyear on 12 May 14
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Testosterone Deficiency, Cardiac Health, and Older Men - 0 views
www.hindawi.com/...143763
low T Testosterone obesity type II diabetes diabetes health wellness metabolic syndrome lipids cholesterol hypogonadism TDS testicular dysgenesis syndrome men male hormone hormones prostate cancer
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Studies have shown pharmacological doses of testosterone to relax coronary arteries when injected intraluminally [39] and to produce modest but consistent improvement in exercise-induced angina and reverse associated ECG changes [40]. The mechanism of action is via blockade of calcium channels with effect of similar magnitude to nifedipine
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men with chronic stable angina pectoris, the ischaemic threshold increased after 4 weeks of TRT and a recent study demonstrates improvement continuing beyond 12 months [
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Studies have shown an inverse relationship between serum testosterone and fasting blood glucose and insulin levels
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Medications such as chronic analgesics, anticonvulsants, 5ARIs, and androgen ablation therapy are associated with increased risk of testosterone deficiency and insulin resistance
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Women with T2D or metabolic syndrome characteristically have low SHBG and high free testosterone
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The precise interaction between insulin resistance, visceral adiposity, and hypogonadism is, as yet, unclear but the important mechanisms are through increased aromatase production, raised leptin levels, and increase in inflammatory kinins
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Men should be encouraged to combine aerobic exercise with strength training. As muscle increases, glucose will be burned more efficiently and insulin levels will fall. A minimum of 30 minutes exercise three times weekly should be advised
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studies now clearly show that low testosterone leads to visceral obesity and metabolic syndrome and is also a consequence of obesity
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In the case of MMAS [43], a baseline total testosterone of less than 10.4 nmol/L was associated with a greater than 4-fold incidence of type 2 diabetes over the next 9 years
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Low testosterone predicts increased mortality and testosterone therapy improves survival in 587 men with type 2 diabetes
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A similar retrospective US study involved 1031 men with 372 on TRT. The cumulative mortality was 21% in the untreated group versus 10% ( ) in the treated group with the greatest effect in younger men and those with type 2 diabetes
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the presence of ED has been shown to be an independent risk factor, particularly in hypogonadal men, increasing the risk of cardiac events by over 50%
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A recent online publication on ischaemic heart disease mortality in men concluded optimal androgen levels are a biomarker for survival
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A recent 10 year study from Western Australia involving 3690 men followed up from 2001–2010 concluded that TT and FT levels in the normal range were associated with decreased all-cause and cardiovascular mortality, for the first time suggesting that both low and DHT are associated with all-cause mortality and higher levels of DHT reduced cardiovascular risk
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The effect of treatment with TRT reduced the mortality rate of treated cohort (8.4%) to that of the eugonadal group whereas the mortality for the untreated remained high at 19.2%
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Men with angiographically proven CAD (coronary artery disease) have significantly lower testosterone levels [29] compared to controls ( ) and there was a significant inverse relationship between the degree of CAD and TT (total testosterone) levels
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men treated with long acting testosterone showed highly significant reductions in TC, LDL, and triglycerides with increase in HDL, associated with significant reduction in weight, BMI, and visceral fat
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In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
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TRT has been shown to upregulate PDE5 [65] and enhance the effect of PDE5Is (now an accepted therapy for both ED and LUTS), it no longer seems logical to advice avoidance of TRT in men with mild to moderate BPH.
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Several meta-analyses have failed to show a link between TRT and development of prostate cancer [66] but some studies have shown a tendency for more aggressive prostate cancer in men with low testosterone
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low bioavailable testosterone and high SHBG were associated with a 4.9- and 3.2-fold risk of positive biopsy
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Current EAU, ISSAM, and BSSM guidance [1, 2] is that there is “no evidence TRT is associated with increased risk of prostate cancer or activation of subclinical cancer.”
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Men with prostate cancer, treated with androgen deprivation, develop an increase of fat mass with an altered lipid profile
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Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
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shared by Nathan Goodyear on 27 Jul 14
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Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Dis... - 0 views
www.ncbi.nlm.nih.gov/...PMC3448089
dysbiosis diet nutrition metabolic endotoxemia disease inflammation gut
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The gut microbiota participates in the body’s metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders
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Firmicutes and Bacteroidetes represent the two largest phyla in the human and mouse microbiota and a shift in the ratio of these phyla has been associated with many disease conditions, including obesity
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there is conflicting evidence on the composition of the obese microbiota phenotype with regards to Bacteroidetes and Firmicutes ratios
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Bifidobacteria spp. from the phyla Actinobacteria, has been shown to be depleted in both obese mice and human subjects
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While it is not yet clear which specific microbes are inducing or preventing obesity, evidence suggests that the microbiota is a factor.
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targeted manipulation of the microbiota results in divergent metabolic outcomes depending on the composition of the diet
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The microbiota has been linked to insulin resistance or type 2 diabetes (T2D) via metabolic syndrome and indeed the microbiota of individuals with T2D is also characterized by an increased Bacteroidetes/Firmicutes ratio, as well as an increase in Bacillus and Lactobacillus spp
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It was also observed that the ratio of Bacteriodes-Prevotella to C. coccoides-E. rectale positively correlated with glucose levels but did not correlate with body mass index [80]. This suggests that the microbiota may influence T2D in conjunction with or independently of obesity
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In humans, high-fat Western-style diets fed to individuals over one month can induce a 71% increase in plasma levels of endotoxins, suggesting that endotoxemia may develop in individuals with GI barrier dyfunction connected to dysbiosis
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LPS increases macrophage infiltration essential for systemic inflammation preceding insulin resistance, LPS alone does not impair glucose metabolism
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early treatment of dysbiosis may slow down or prevent the epidemic of metabolic diseases and hence the corresponding lethal cardiovascular consequences
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increased Firmicutes and decreased Bacteroidetes, which is the microbial profile found in lean phenotypes, along with an increase in Bifidobacteria spp. and Lactobacillus spp
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mouse and rat models of T1D have been shown to have microbiota marked by decreased diversity and decreased Lactobacillus spp., as well as a decrease in the Firmicutes/Bacteroidetes ratio
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The microbiota appears to be essential in maintaining the Th17/Treg cell balance in intestinal tissues, mesenteric and pancreatic lymph nodes, and in developing insulitis, although progression to overt diabetes has not been shown to be controlled by the microbiota
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Lactobacillus johnsonii N6.2 protects BB-rats from T1D by mediating intestinal barrier function and inflammation [101,102] and a combination probiotic VSL#3 has been shown to attenuate insulitis and diabetes in NOD mice
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breast fed infants have higher levels of Bifidobacteria spp. while formula fed infants have higher levels of Bacteroides spp., as well as increased Clostridium coccoides and Lactobacillus spp
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In mice fed a diet high in fat, there are many key gut population changes, such as the absence of gut barrier-protecting Bifidobacteria spp
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diet has a dominating role in shaping gut microbiota and changing key populations may transform healthy gut microbiota into a disease-inducing entity
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“Western” diet, which is high in sugar and fat, causes dysbiosis which affects both host GI tract metabolism and immune homeostasis
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THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: result... - 0 views
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shared by Nathan Goodyear on 02 Mar 15
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Testosterone and metabolic syndrome Cunningham GR - Asian J Androl - 0 views
www.ajandrology.com/article.asp
Testosterone metabolic syndrome MetS TT total Testosterone SHBG men male hormone hormones Estradiol insulin resistance
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The relationship of low testosterone to MetS often is considered to be bidirectional; however, the relationships probably are not direct
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Many of the components of the MetS are recognized risk factors for the development of cardiovascular disease (CVD)
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Multiple cross-sectional studies have found low TT and low sex hormone binding globulin (SHBG) levels in Caucasian and African-American men with the MetS, irrespective of age
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Estradiol levels are increased in men with the MetS, and they are positively correlated with the number of abnormal components of the MetS.
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Although it is known that estrogen will increase SHBG levels, apparently the hyperinsulinism associated with obesity has a greater effect on SHBG levels
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Inflammatory cytokines are thought to have a direct effect on the pituitary to reduce LH secretion [15] and also a direct effect on Leydig cell secretion of testosterone
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Men in the lowest quartiles of serum TT, calculated free testosterone (cFT) and SHBG at baseline had the highest odds ratios for developing the MetS or DM during the 11 years follow-up
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More recently, investigators conducting population-based studies have reported that only SHBG is associated with future development of the MetS
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Additional evidence that low TT increases the risk of MetS comes from androgen deprivation treatment of prostate cancer
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Low TT and low bioavailable testosterone (bT) were each significantly associated with elevated 20 years risk of CVD mortality in an older population in which cause-specific mortality was age, adiposity, and lifestyle-adjusted.
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combination of low bT and ATP III-defined MetS is associated with increased cardiovascular mortality in men aged 40 years and above
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in elderly men, testosterone may weakly protect against CVD. Alternatively, low TT may indicate poor general health
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Muraleedharan and Jones [27] concluded that there is convincing evidence that low T is a biomarker for disease severity and mortality.
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It is widely recognized that testosterone treatment can reduce fat mass and increase lean body mass; however, until recently most reports have not been associated with much weight loss
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Changes in body composition and weight loss are considered potential mechanisms by which testosterone treatment improves insulin sensitivity and glucose control in patients with diabetes. Effects on inflammatory cytokines [38] and changes in oxidative metabolism [39] also have been reported to improve glucose metabolism.
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Testosterone replacement therapy has been reported to improve some or all of the components of the MetS.
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shared by Nathan Goodyear on 30 Mar 15
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Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views
www.ncbi.nlm.nih.gov/...PMC4364844
low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome
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defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
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the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
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most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
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Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
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−0.124 nmol/L/year in serum total testosterone
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In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
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In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
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testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
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testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
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In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
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independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
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Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
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In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
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leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
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Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
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Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
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As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
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alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
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A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
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Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
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subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
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In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
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Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
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HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
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pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
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In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
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Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
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Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
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The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
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In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
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a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
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the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
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assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
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In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
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a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
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A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
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most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
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MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
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Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
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In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
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weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
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To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
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In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
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low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
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Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
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low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
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European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
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Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
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serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
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Nice review of Testosterone levels and some of the evidence linking Diabetes with low T. However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling. The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
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The adipose tissue metabolism: role of testosterone and dehydroepiandrosterone. - PubMe... - 0 views
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T inhibits lipid uptake and lipoprotein-lipase (LDL) activity in adipocytes, and stimulates lipolysis
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DHEA stimulates resting metabolic rate (RMR) and lipid oxidation, and enhances glucose disposal, by increasing the expression of GLUT-1 and GLUT-4 on fat cell plasma membrane
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The insulin-like effect of DHEA would be associated to a decrease of plasma insulin concentrations and, thus, to an increase of the molar ratio between lipolytic hormones and insulin
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the fat-reducing effect of both T and DHEA seems to be more evident at the level of visceral adipose tissue
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Testosterone inhibits lipid uptake into adipocytes. Testosterone inhibits lipoprotein lipase. Testosterone stimulated lipolysis. Testosterone inhibits adipocyte differentiation of proginator cells. DHEAs effects are through different mechanisms. Both have a preference for activity with visceral adipose tissue.
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Testosterone deficiency syndrome and cardiovascular health: An assessment of beliefs, k... - 0 views
www.ncbi.nlm.nih.gov/...PMC3929476
low T Testosterone cardiovascular disease physicians men male hormone hormones
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Testosterone deficiency has a prevalence of 7% in the general population, rising to 20% in elderly males
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Males with CAD have lower testosterone levels than those with normal coronary angiograms of the same age,5 suggesting that the prevalence of testosterone deficiency is much higher in the CAD population
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Men with hypertension, another established risk factor for CAD, have lower testosterone compared to normotensive men
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Recent meta-analyses showed that testosterone levels are generally lower among patients with metabolic syndrome, regardless of the various definitions of metabolic syndrome that are used
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Testosterone (total and bioavailable) and sex-hormone binding globulin (SHBG) are inversely associated with the prevalence of metabolic syndrome in men between the ages of 40 and 80, and this association persists across racial and ethnic backgrounds
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Low testosterone levels have been related to increased insulin resistance and cardiovascular mortality,12 even in the absence of overt type 2 diabetes mellitus.
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testosterone levels (total and bioavailable) in middle-aged men are inversely correlated with insulin resistance
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The Massachusetts Male Aging Study (MMAS) demonstrated that low levels of testosterone and SHBG are independent risk factors for the development of type 2 diabetes,
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There is an inverse linear correlation between body mass index (BMI) and wait-to-hip ratio with testosterone and insulin-like growth factor-1 levels.
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Testosterone supplementation for 1 year in hypogonadal men has been shown to cause a significant improvement in body weight, BMI, waist size, lipid profile, and C-reactive protein levels
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TRT for 3 months in hypogonadal men with type 2 diabetes significantly improved fasting insulin sensitivity, fasting blood glucose and glycated hemoglobin.
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Testosterone replacement can improve angina symptoms and delay the onset of cardiac ischemia, likely through a coronary vasodilator mechanism
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ADT is associated with an increased risk of cardiovascular events, including myocardial infarction and cardiovascular mortality.
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ADT significantly increases fat mass, decreases lean body mass,29,30 increases fasting plasma insulin and decreases insulin sensitivity31 and increases serum cholesterol and triglyceride levels
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Startling study on the knowledge of Testosterone and cardiovascular disease in general practitioners and cardiologists in Canada. Eight-eight percent did not screen patients with cardiovascular disease for low Testosterone. A whopping 67% of physicians did not know that low T was a risk factor for cardiovascular disease, yet 62% believed Testosterone would increase exercise tolerance. The lack of knowledge displayed by physicians today is staggering and is an indictment of the governing bodies. This was a survey conducted in Canada so there are obvious limitations to the strength/conclusion of this study.
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International Journal of Impotence Research - Obesity, low testosterone levels and erec... - 0 views
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low T low Testosterone men male hormone hormones ED erectile dysfunction Testosterone diabetes metabolic syndrome obesity
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Studies have shown that ED may be an early biomarker of general endothelial dysfunction, atherosclerosis and CVD
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testosterone treatment of hypogonadal young and older men improves sexual function, increases lean mass and decreases fat mass
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In men with low serum testosterone (for example, <8 or 230 nmol l−1) with obesity, metabolic syndrome and diabetes mellitus, treatment with testosterone is warranted
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In obese middle-aged men, testosterone treatment reduced visceral adipocity, insulin resistance, serum cholesterol and glucose levels
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testosterone replacement has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure in hypogonadal men with the metabolic syndrome as well as type 2 diabetes mellitus
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Testosterone significantly inhibits lipoprotein lipase activity, which reduces triglycerides uptake into adipocytes in the abdominal adipose tissue
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testosterone treatment decreased endogenous inflammatory cytokines (tumor necrosis factor-α and IL-1β) and lipids (total cholesterol) and increased IL-10 in hypogonadal men
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Testosterone treatment reduced leptin and adiponectin levels in hypogonadal type 2 diabetic men after 3 months of testosterone replacement
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Obesity adversely affects endothelial function and lowers serum testosterone levels through the development of insulin resistance and metabolic syndrome
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Metabolic disturbances as well as production of cytokines and adipokines by inflamed fat cells may be causal factors in the development of ED
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The onset of ED and the associated risk of CVD may be delayed through lifestyle modifications that affect obesity, such as diet and exercise
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Very low testosterone levels contribute to the development of ED in obesity, metabolic syndrome and type 2 diabetes mellitus
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Obesity is associated with low total testosterone levels that can be explained at least partially by lower sex hormone-binding globulin (SHBG) in obese men
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epidemiological studies have shown a negative correlation between BMI and total testosterone and to a lesser extent with free and bioavailable (biologically active) testosterone levels