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Nathan Goodyear

Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 di... - 0 views

  • up to 40% of men with T2DM have testosterone deficiency
  • Among diabetic patients, a reduction in sex hormone binding globulin levels induced by insulin resistance leads to a further decline of testosterone levels
  • 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)
  • 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.
  • testosterone administration could increase muscle mass and strength
  • 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
  • The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway
  • 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
  • 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
  • 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.
  • TRT reduced triglyceride levels
  • TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men
  • a recent meta-analysis showed that statins could significantly lower testosterone concentrations.
  • 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.
  • 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.  
Nathan Goodyear

The heritability of circulating testosterone, oestradiol, oestrone and sex hormone bind... - 0 views

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    No surprise here as genetics and environment play in a role in all disease.  Here it is hormones.  
Nathan Goodyear

Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN,... - 0 views

  • The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
  • Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
  • By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
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  • diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
  • bariatric surgery achieves 10%-30% long-term weight loss in controlled studies
  • The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
  • Reductions in testosterone levels correlate with the severity of obesity and men
  • epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
  • healthy ageing by itself is uncommonly associated with marked reductions in testosterone levels
  • obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
  • Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
  • although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
  • SHBG increases with age
  • marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
  • adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
  • diabetic obesity is associated with decreases in circulatory E 2
  • In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
  • In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
  • weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
  • fat is androgen-responsive
  • low testosterone may augment the effects of a hypercaloric diet
  • In human male ex vivo adipose tissue, testosterone decreased adipocyte differentiation by 50%.
  • Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
  • in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
  • severe sex steroid deficiency can increase fat mass rapidly
  • bidirectional relationship between testosterone and obesity
  • increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
  • androgens may play a more significant role in VAT than SAT
  • men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
    • Nathan Goodyear
       
      Interesting: low T increases VAT, yet T therapy does not reduce VAT, yet T therapy reduces SAT.
  • irisin, derived from muscle, induces brown fat-like properties in rodent white fat
  • androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
  • low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
  • pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
  • Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
  • observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
  • genuine reactivation of the HPT axis in obese men requires more substantial weight-loss
  • A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
  • men, regardless of obesity level, can benefit from the effect of weight loss.
  • inconsistent effect of testosterone on VAT
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    to be read
Nathan Goodyear

Sex Hormone Binding Globulin and the Assessment of Androgen Status - 0 views

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    good review of SHBG
Nathan Goodyear

Sex Hormone-Binding Globulin, but Not Testosterone, Is Associated Prospectively and Ind... - 0 views

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    SHBG associated with increased metabolic syndrome risk, not Testosterone in this study.  Total Testosterone, when low, has been suggested to be more predictive of Mets than free T.
Nathan Goodyear

Low Sex Hormone-Binding Globulin, Total Testosterone, and Symptomatic Androgen Deficien... - 0 views

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    Low Total Testosterone, low SHBG, and symptoms of low T are associated with an increase risk (relative) of Mets, especially in normal weight men.
Nathan Goodyear

Testosterone deficiency syndrome and cardiovascular health: An assessment of beliefs, k... - 0 views

  • The vast majority (88%) did not screen cardiac patients for TDS.
  • Testosterone deficiency has a prevalence of 7% in the general population, rising to 20% in elderly males
  • 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
  • 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
  • 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
  • ower levels of testosterone and SHBG predict a higher incidence of metabolic syndrome.
  • Low testosterone levels have been related to increased insulin resistance and cardiovascular mortality,12 even in the absence of overt type 2 diabetes mellitus.
  • testosterone levels (total and bioavailable) in middle-aged men are inversely correlated with insulin resistance
  • 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,
  • Andropausal men (age 58 ± 7 years) have a higher maximal carotid artery intima-media thickness
  • 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.
  • 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
  • TRT for 3 months in hypogonadal men with type 2 diabetes significantly improved fasting insulin sensitivity, fasting blood glucose and glycated hemoglobin.
  • Testosterone replacement can improve angina symptoms and delay the onset of cardiac ischemia, likely through a coronary vasodilator mechanism
  • ADT is associated with an increased risk of cardiovascular events, including myocardial infarction and cardiovascular mortality.
  • 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.
Nathan Goodyear

Sex hormone binding globulin, but not testosterone, is associated with the metabolic sy... - 0 views

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    This study finds an association between low SHBG and increased metabolic syndrome in obese women with PCOS.  Testosterone was not associated.  Other studies have shown a positive association between Testosterone and MetS in women.  This follows men in that SHBG shows an association with MetS.  Only the abstract is present here, so I can't look at the data presented.
Nathan Goodyear

Estradiol Activates the Prostate Androgen Receptor and Prostate-specific Antigen Secret... - 0 views

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    Estradiol increases PSA secretion.
Nathan Goodyear

Sex Hormone-Binding Globulin and the Free Androgen Index Are Related to Cardiovascular ... - 0 views

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    A decrease in the SHBG in post menopause women is associated with increase in free Testosterone, which is associated with increase in MetS and CVD
Nathan Goodyear

Low Sex-Hormone Binding Globulin is Associated with the Metabolic Syndrome in Postmenop... - 0 views

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    Post menopause associated with lower SHBG, increase in free Testosterone and increase in metabolic syndrome.
Nathan Goodyear

Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic rev... - 0 views

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    large meta analysis finds low Total Testosterone associated with in men and high Total Testosterone associated with MetS in women.  lower SHBG is associated with MetS
Nathan Goodyear

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower level... - 0 views

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    Age increases SHBG.  This study doesn't find a correlation with non-SHBG Testosterone in "health" men.  The term health is probably key.
Nathan Goodyear

The association between hyperandrogenemia and the metabolic syndrome in morbidly obese ... - 0 views

  • a significant inverse relationship between HA and HDL-cholesterol levels which is in accordance with previous studies of women with PCOS
  • HA was associated with 61 % increased adjusted odds of MetS, and that this association was mainly driven by increased odds of dysglycemia and dyslipidemia
  • the prevalences of MetS, PCOS and HA were high among morbidly obese women <50 years of age
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  • Compared to women without HA, those with HA had significantly higher odds of having the MetS, which was mainly explained by the associations between HA and the lipid- and glucose components of the MetS
  • FTI-blood test might add value to the cardiovascular risk assessment of premenopausal women with morbid obesity
  • We calculated the free testosterone index (FTI) using the formula: FTI = 100 x serum testosterone (nmol/L) / sex hormone binding globulin (SHBG, nmol/L)
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    Another study that finds hyperandrogenism in women is associated with increased Metabolic Syndrome.  This study found obesity was associated with increased hyperandrogegism and Metabolic Syndrome irregardless of PCOS diagnosis or not.
Nathan Goodyear

Effects of endurance exercise on free testosterone concentration and the binding affini... - 0 views

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    exercise increases Testosterone production via catecholamine mechanism.  Free Testosterone increases independent from SHBG affinity.
Nathan Goodyear

A Radioimmunoassay for 3,3',5'-L-Triiodothyronine (Reverse T3): Assessment of Thyroid G... - 0 views

  • Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis.
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    oral estrogen supplementation increase reverse T3 and lowers metabolism and leads to weight gain
Nathan Goodyear

Sex hormone-binding globulin is a major dete... [Atherosclerosis. 2005] - PubMed - NCBI - 0 views

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    SHBG positively associated with HDL and negatively associated with triglycerides.
Nathan Goodyear

Serum sex hormone-binding globulin and test... [Eur J Endocrinol. 2014] - PubMed - NCBI - 0 views

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    SHBG positively associated with lower CVD risk profile, CRP, blood pressure, TC, triglycerides..., in young men.  This was found independent of Testosterone.  This is similar to a lot of the research on Metabolic Syndrome as well.
Nathan Goodyear

Race differences in obesity and its relationship to the sex hormone milieu : Hormone Mo... - 0 views

  • increased abdominal and visceral adipose tissue (VAT) – found in women and marked by low sex hormone binding globulin (SHBG) and high bioavailable testosterone (BT) – is related to the metabolic risk profile
  • In men, increased BT is related to decreased abdominal obesity and a decrease in the metabolic risk profile
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    Only abstract available here.  Race (black vs white) is associated with changes in obesity effects on adrogenicity, particularly in women.  One wonders if this is a result of other variables i.e.vitamin D.
Nathan Goodyear

Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome ... - 0 views

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    low SHBG found to be more associated with metabolic syndrome in older men than low Testosterone.  The study consisted of 2502 men older than 70.  The authors proposed this occurs through the relationship between SHBG and insulin sensitivity.  I think that is a little too simplistic.
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