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Nathan Goodyear

Testosterone Deficiency, Cardiac Health, and Older Men - 0 views

  • 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
       
      This directly refutes the recent studies (3) that Testosterone therapy increases cardiovascular events.
    • Nathan Goodyear
       
      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
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  • 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
       
      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
  • A decline was noted in IL6 and TNF-alpha
  • In some studies, a decline in diastolic blood pressure has been observed, after 3–9 months [24, 26] and in systolic blood pressure
  • In the Moscow study, C-reactive protein was reduced by TRT at 30 weeks versus placebo
  • 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
       
      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
       
      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
Nathan Goodyear

Will testosterone replacement therapy become a new treatment of chronic heart failure? ... - 0 views

  • TRT could improve significantly the exercise capacity of patients, compared with placebo
  • it could be seen that the effect of TRT on SBP and DBP was controversial
  • in men with congestive heart failure, testosterone reduced the Q-Td, whereas placebo had no effects
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  • The MVC and PTmax were significantly improved in TRT patients but remained unchanged in the placebo group
  • handgrip strength improved significantly with testosterone treatment
  • According to EF assessed by echocardiography, no differences were observed between the patients who were prescribed testosterone and those who received placebo
  • There were no differences between the groups in circulating levels of NT pro-BNP, and inflammatory markers were unchanged, except for a decrease in TNF-α from baseline in the placebo group
  • Testosterone supplementation therapy appeared to be safe, and the subjects who accepted testosterone treatment did not appear any obvious adverse reactions.
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    Testosterone therapy in men with CHF found to increase exercise capacity, reduced the Q-T interval in men, improved muscle strength in men, and was found to be safe in meta-analysis.
Nathan Goodyear

Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in M... - 0 views

  • Azad et al [15] used single photon emission computed tomography and showed that, after 3~5 weeks of TRT, cerebral perfusion was increased in the midbrain and the superior frontal gyrus in seven men with hypogonadism
  • After 12~14 weeks, increased perfusion was still observed in the midbrain as well as in the midcingulate gyrus
  • TDS patients who received TRT showed significant improvement in cognitive function only if mild cognitive impairment was present at baseline
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  • Cherrier et al [17] evaluated a sample of 32 subjects, which included 17 men with mild cognitive impairment and 15 with Alzheimer's disease. At the 6-week follow-up, patients who received TRT showed significantly better scores regarding spatial memory, constructional abilities, and verbal memory compared to those noted in the placebo group. Taken together, these results suggest that TRT has a beneficial effect on cognitive function
  • TRT improved mood and well-being, and reduced fatigue and irritability in hypogonadal men
  • The study by Pope et al [20] involved men with depression refractory to standard anti-depressants, and found that TRT lowered the Hamilton Depression score,
  • depression tends to increase as testosterone levels decrease [21], it is highly likely that TRT improved symptoms of depression by increasing testosterone levels.
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    men with Testosterone <300 ng/dl with levels after 8 months of therapy achieving +680 ng/dl.
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

Phthalate-Induced Pathology in the Foetal Testi... [Reproduction. 2013] - PubMed - NCBI - 0 views

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    This study found a 2 fold increased in estradiol levels in rats exposed to phthalates in-utero.  This could have been due to increased aromatase activity and/or xenoestrogenic effect.  This study proposes a link between phthalate exposure in-uteruo, increased estrogen production and testicular dysgenesis syndrome.  Take home: in this model male testicles were altered prior to birth by phthalate exposure.
Nathan Goodyear

Predicting the long-term risk of tardive dyskinesi... [J Clin Psychiatry. 1993] - PubMe... - 0 views

  • , we estimate the risk of persistent TD to be 32% after 5 years of neuroleptic exposure (95% confidence interval [CI] = 23%-43%), 57% after 15 years of exposure (95% CI = 47%-66%), and 68% after 25 years of exposure
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    Neuroleptics significantly increase risk of Tardive Dyskinesias: we should think before we prescribe
Nathan Goodyear

Testosterone deficiency and cardiovascular mortality Morgentaler A, - Asian J Androl - 0 views

  • overall mortality and CV mortality were inversely associated with serum T concentrations.
  • men with low serum T, defined as &lt; 8.7 nmol l−1 (250 ng dl−1 ), demonstrated significantly greater all-cause mortality than men with higher serum T (hazard ratio [HR]: 2.24; 95% CI: 1.41-3.57), as well as greater CV mortality
  • lower T levels were significantly associated with the presence of any CV disease
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  • more than 30 years of studies suggesting that low levels of T represent an increased risk for CV and overall mortality,
  • lower serum T concentrations also are associated with CV disease, including incident coronary artery disease [17],[18],[19] and atherosclerosis,
  • the actual rate of adverse events was only half as great in the T group (123 events in 1223 men at risk = 10.1%) as in the untreated group (1587 events in 7486 men = 21.2%)
  • The study by Vigen et al. [7] has already undergone two published corrections,
  • 29 medical societies have called for retraction of the article, asserting "gross data mismanagement and contamination," that rendered the study "no longer credible
  • Mortality in T-treated men was reduced by approximately half in treated men compared with untreated men, at 10.3% versus 20.7%, respectively
  • The mortality rate for men who received TTh was 3.4 deaths per 100 person-years, and 5.7 deaths per 100 person-years in untreated men
  • HR of 0.61 (95%CI: 0.42-0.88; P = 0.008), indicating a significant reduction in mortality with TTh
  • men in the highest prognostic MI risk quartile, treatment with TTh was associated with reduced risk
  • tripling in T prescriptions in the US over the last decade
  • a majority of observational studies have found that low endogenous serum T levels are associated with increased mortality.
  • Men who received TTh were able to exercise significantly longer without ischemia compared with men who received placebo
  • In men with congestive heart failure, those who received T demonstrated greater walking distance and other functional endpoints compared with those who received placebo
  • TTh has been shown uniformly and repeatedly to improve several known CV risk factors, including reduced fat mass, body fat percent, and waist circumference, and increased lean mass
  • improved glycemic control
  • reductions in insulin resistance.
  • the evidence strongly points to improved CV status with normal serum T or treatment with TTh in men with TD
  • analysis of health insurance claims data that reported a 36% increased rate of nonfatal MI in the 90d following receipt of a T prescription compared with the 12 prior months.
  • Comparison with men who received a prescription for a phosphodiesterase type 5 inhibitor (PDE5i) revealed no increased rate of MI following the prescription
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    Great review by Morgentaler of Testosterone and CVD.  He highlights the significant flaws in the JAMA and the NEJM articles of Testosterone therapy risks.  Morgentaler highlights the significant evidence that points to low T and increased risk of CVD. On contention I have, is Morgantaler seems to flip aside the massive uptick of Testosterone use in the US as compared to other countries.  The evidence definitely points to Testosterone therapy as being safe in those with low T, but there is definitely a problem of significant Testosterone doping that is taking place as well.
Nathan Goodyear

Marked Testosterone Deficiency-Related Symptoms Ma... [J Sex Med. 2014] - PubMed - NCBI - 0 views

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    The more severe the symptoms, the more the increased risk of CVD in men with low T.
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