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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 < 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
  • ...19 more annotations...
  • 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

Testosterone and benign prostatic hyperplasia Jarvis TR, Chughtai B, Kaplan SA, - Asian J Androl - 0 views

  • The prevalence of hypogonadism (often defined as serum testosterone < 300 ng dl−1 ) ranges from 6% [10] to as high as 38%
  • The process of BPH, however, continues as men age and despite the fact their serum testosterone decreases
  • Liu et al. [12] demonstrated that in a group of older males (mean age 59.8 years) that there was not a significant correlation of serum testosterone levels (total, free or bioavailable) with either prostate volume or International Prostate Symptom Score (IPSS)
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  • in eugonadal men, studies have demonstrated that the prostate can increase in volume by approximately 12%
  • There seems to be little doubt that the treatment with testosterone of a young hypogonadal male leads to significant growth of the prostate
  • Behre et al. [22] demonstrated increased prostate volume and prostate-specific antigen (PSA) levels in hypogonadal men
  • Most studies, however, have shown no effect of exogenous androgens on PSA or prostate volume for older hypogonadal males
  • They argue that the prostate is relatively insensitive to changes in androgen concentration at normal levels or in mild hypogonadism because the AR is saturated by androgens and therefore maximal androgen-AR binding is achieved. Conversely, the prostate is very sensitive to changes in androgen levels when testosterone is low
  • saturation model
  • visceral obesity (one of the most significant components of metabolic syndrome) is associated with prostate volume and influences prostate growth during TRT.
  • This hypothesis of inflammation induced LUTS is also argued to be a mechanism for improvement of LUTS with PDE5I
  • The concept, therefore, that treatment with TRT of hypogonadal males with metabolic syndrome might lead to improvement/stabilization of their LUTS, appears to be confirmed in recent work by Francomano et al.
  • There was also an improvement in components of the patient's metabolic syndrome (such as BMI, waist circumference, hemoglobin A1c [HbA1c], insulin sensitivity, and lipid profile) as well as inflammatory markers and C-reactive protein.
  • They concluded that TRT was safe in this group of men, and hypothesize that TRT mitigates the pro-inflammatory factors associated with metabolic syndrome.
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    Authors review the literature behind Testosterone and BPH.  The authors highlight the 4 proposed theories behind BPH: Testosterone, Estrogen, inflammation, and metabolic.   The conclusion is mixed: pointing out that no high level of evidence exists on either side of the debate of Testosterone and BPH.
Nathan Goodyear

Phosphodiesterase, cAMP, and cGMP - 0 views

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    Not a study, but just a nice descriptive slide.
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