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Nathan Goodyear

Endocrinology of the Aging Male - 0 views

www.ncbi.nlm.nih.gov/...PMC3073592

aging male hormone hormones

shared by Nathan Goodyear on 30 Apr 13 - No Cached
  • All steps beyond the formation of pregnenolone take place in the smooth endoplasmic reticulum
  • Cytochrome P450 enzyme, CYP11A is located on the inner mitochondrial membrane and catalyses the rate limiting step of pregnenolone synthesis
  • Estrogen and related steroids, thyroid hormone and insulin increase SHBG levels.
  • ...21 more annotations...
  • SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
  • Plasma SHBG levels tend to increase with increasing age
  • The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
  • Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
  • Testosterone is secreted in a pulsatile fashion
  • Current clinical guidelines suggest at least two measurements
  • In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
  • In older men, the diurnal variation is blunted
  • it is standard practice for samples to be obtained between 0800 and 1100 h.
  • Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
  • DHT remains constant despite the decline of its precursor testosterone
  • Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
  • Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
  • DHT showed no cross-sectional age trend
  • Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
  • The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
    • Nathan Goodyear
      Nathan Goodyear on 01 May 13
       
      This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
  • obesity impairs hypothalamic/pituitary function
  • Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
  • Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
  • Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
  • In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
  • Nathan Goodyear on 30 Apr 13
     
    great review of hormone changes associated with aging in men.
Nathan Goodyear

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Lo... - 0 views

press.endocrine.org/...jcem.87.2.8201

low T Testosterone low T low Testosterone male men hormone hormones DHT aging BMI MMAS Massachusetts Male Aging Study

shared by Nathan Goodyear on 11 Aug 14 - No Cached
  • Nathan Goodyear on 11 Aug 14
     
    MMAS study finds an age associated decline in Total Testosterone and free Testosterone levels. This study focus on the % decline based on other variables i.e. age, BMI...IN contrast, a 3.5% rise in DHT levels were observed. There is debate about the correlation of serum DHT and intra-tissue DHT. In fact, studies suggest there is little correlation.
Nathan Goodyear

http://www.imperialendo.co.uk/mohr.pdf - 0 views

www.imperialendo.co.uk/mohr.pdf

MMAS Massachusetts Male Aging Study low T low Testosterone Testosterone

shared by Nathan Goodyear on 07 May 17 - No Cached
  • Nathan Goodyear on 07 May 17
     
    Massachusetts Male Aging Study (MMAS).
Nathan Goodyear

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

www.ajandrology.com/article.asp

Testosterone male obesity overweight men hormone hormones low T Low T

shared by Nathan Goodyear on 15 Jan 14 - No Cached
  • 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
  • ...37 more annotations...
  • 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
      Nathan Goodyear on 16 Jan 14
       
      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
  • Nathan Goodyear on 15 Jan 14
     
    to be read
Nathan Goodyear

Are serum hormones associated with the risk of prostate cancer? Prospective results fro... - 0 views

www.sciencedirect.com/...S009042950001116X

serum blood hormone hormones massachusetts male aging study MMAS prostate cancer

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • Nathan Goodyear on 27 Jan 14
     
    No correlation seen between serum hormones and prostate cancer risk.  Serum evaluation of hormones provides little, if any, clinically, relevant information.  The only association was found with a DHT metabolite--androstanediol.
Nathan Goodyear

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

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • 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
  • ...14 more annotations...
  • 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
  • Nathan Goodyear on 03 Mar 14
     
    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

Prevalence and Incidence of Androgen Deficiency in Middle-Aged and Older Men: Estimates... - 0 views

jcem.endojournals.org/...5920.full

lot T testosterone Massachusetts male aging study MMAS hypogonadism

shared by Nathan Goodyear on 20 Nov 13 - No Cached
  • Nathan Goodyear on 20 Nov 13
     
    The Massachusetts male aging study found 2.4 million men with hypogonadism.  They estimated 481,000 new cases annually in the age group of 40-69.  This was in very stringent definition of "hypogonadism".
Nathan Goodyear

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

shared by Nathan Goodyear on 12 May 14 - No Cached
  • 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
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      This directly refutes the recent studies (3) that Testosterone therapy increases cardiovascular events.
    • Nathan Goodyear
      Nathan Goodyear on 13 May 14
       
      Testosterone acts as a calcium channel blocker inducing vasodilation.
  • 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 [
  • Exercise capacity in men with chronic heart failure increased after 12 weeks
  • ...36 more annotations...
  • Studies have shown an inverse relationship between serum testosterone and fasting blood glucose and insulin levels
  • Medications such as chronic analgesics, anticonvulsants, 5ARIs, and androgen ablation therapy are associated with increased risk of testosterone deficiency and insulin resistance
  • Women with T2D or metabolic syndrome characteristically have low SHBG and high free testosterone
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      This stands in polar opposite of that with men.
  • Hypogonadism is a common feature of the metabolic syndrome
  • 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
  • levels of testosterone are reduced in proportion to degree of obesity
  • 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
  • Testosterone increases levels of fast-twitch muscle fibres
  • By increasing testosterone, levels of type 2 fibres increase and glucose burning improves
  • Weight loss will increase levels of testosterone
  • studies now clearly show that low testosterone leads to visceral obesity and metabolic syndrome and is also a consequence of obesity
  • 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
  • There is high level evidence that TRT improves insulin resistance
  • Low testosterone predicts increased mortality and testosterone therapy improves survival in 587 men with type 2 diabetes
  • 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
  • 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%
  • A recent online publication on ischaemic heart disease mortality in men concluded optimal androgen levels are a biomarker for survival
  • inverse associations between low TT or FT (Table 2) and the severity of CAD
  • 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
  • TDS is associated with increased cardiovascular and all-cause mortality
  • 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%
  • hypogonadal men had slightly increased triglycerides and HDL
  • 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
  • TRT has also been shown to reduce fibrinogen to levels similar to fibrates
  • 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
  • Low androgen levels are associated with an increase in inflammatory markers
  • In the Moscow study, C-reactive protein was reduced by TRT at 30 weeks versus placebo
  • In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
  • A decline was noted in IL6 and TNF-alpha
  • No studies to date show an increase in LUTS/BPH symptoms with higher serum testosterone levels
  • 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.
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      What about just starting with normalization of Testosterone levels first.
  • 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
    • Nathan Goodyear
      Nathan Goodyear on 12 May 14
       
      And if one would have looked at their estrogen levels, I guarantee they would have been found to be elevated.
  • low bioavailable testosterone and high SHBG were associated with a 4.9- and 3.2-fold risk of positive biopsy
  • 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.”
  • Men with prostate cancer, treated with androgen deprivation, develop an increase of fat mass with an altered lipid profile
  • 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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