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Nathan Goodyear

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

www.ajandrology.com/preprintarticle.asp

testosterone low t low Testosterone CVD cardiovascular mortality therapy

shared by Nathan Goodyear on 01 Dec 14 - No Cached
  • 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
  • Nathan Goodyear on 01 Dec 14
     
    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, cardiovas... [Best Pract Res Clin Endocrinol Metab. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21397202

low T low testosterone T CV cardiovascular disease CVD MetS metabolic syndrome

shared by Nathan Goodyear on 10 Nov 12 - No Cached
  • Nathan Goodyear on 10 Nov 12
     
    low T is associated with increased risk of CV death.  Additionally, Testosterone therapy shown to improve MetS.
Nathan Goodyear

Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study - 0 views

eje-online.org/...687.long

low T low T testosterone CVD cardiovascular mortality men Estradiol E2

shared by Nathan Goodyear on 10 Nov 12 - No Cached
  • Nathan Goodyear on 10 Nov 12
     
    meta-analysis finds that low T associated with increased cardiovascular mortality in men.  Additionally, higher Estradiol is associated with increased CVD and CV mortality
Nathan Goodyear

Persistent Subclinical Hypothyroidism and Cardiovascular Risk in the Elderly: The Cardi... - 0 views

jcem.endojournals.org/...533.abstract

subclinical hypothyroidism TSH cardiovascular elderly health

shared by Nathan Goodyear on 08 Feb 13 - No Cached
  • Nathan Goodyear on 08 Feb 13
     
    study finds no increased risk of CHD, HF, or CV death in subclinical hypothyroidism in older adults.  No insight is gained from this article, due to the use of TSH as the only tool for thyroid assessment.  TSH has been shown to become unreliable as a sole thyroid assessment tool an aging population.
Nathan Goodyear

High serum testosterone is associated with... [J Am Coll Cardiol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21982312

Testosterone low T therapy treatment men CVD cardiovascular disease

shared by Nathan Goodyear on 31 Jul 12 - No Cached
  • Nathan Goodyear on 31 Jul 12
     
    Testosterone inversely associated with CV events in men.  Low T is not just for ED, but should be a part of CVD prevention.
Nathan Goodyear

Effects of androgen supplementation of hormone... [Fertil Steril. 2001] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11476766

Testosterone women female hormones hormone CVD cardiovascular disease health lipids

shared by Nathan Goodyear on 20 Mar 14 - No Cached
  • Nathan Goodyear on 20 Mar 14
     
    Testosterone therapy in post menopausal women appears to have adverse cardiovascular effects in women.  The negative effects were an increase in Pulsatility index and adverse change in lipid profiles.  This seemed to counter the positive effects by estrogen.  Others have proposed that combination E2 and T therapy hide the negative effects of testosterone on CV health in women.
Nathan Goodyear

Testosterone, SHBG and cardiovascular health in postmenopausal women - 0 views

dspace.library.uu.nl/...39518

Testosterone women female hormone hormones CVD cardiovascular disease

shared by Nathan Goodyear on 20 Mar 14 - No Cached
  • Nathan Goodyear on 20 Mar 14
     
    Master's thesis reviews Testosterone therapy in women.  The evidence is poor.  What is seen is that low SHBG and increasing Testosterone in the long term appears to be associated with adverse CV effects. Otherwise, the effects of Testosterone are negligible if negative at all.   High dose studies did find increased CVD in women. The dosing here was at 40 mg.
Nathan Goodyear

Beneficial and Adverse Effects of Testosterone on the Cardiovascular System in Men - 0 views

jcem.endojournals.org/...4300.abstract

low T Testosterone male men hormone hormones cardiovascular aging

shared by Nathan Goodyear on 14 Nov 13 - No Cached
  • Nathan Goodyear on 14 Nov 13
     
    pubmed review of 33 years finds mix bag on low T. Low T clearly associated with increased hypertension, dyslipidemia, atherosclerosis, thrombosis, cardiac dysfunction, and CV events.  Studies on Testosterone therapy in resolution of these dysfunctions are low.  This article claims there is a lack of evidence.  That is not true.  
Nathan Goodyear

Testosterone therapy may not be associated with CV risk : Clinical Endocrinol... - 0 views

www.clinicalendocrinologynews.com/...0c4108e7209b1477f2d4a8e3b.html

testosterone therapy treatment low T men male hormone hormones

shared by Nathan Goodyear on 28 May 14 - No Cached
  • Nathan Goodyear on 28 May 14
     
    another press article on the recent publication out of the low T clinics.  The conclusion statement says it all: "I don't think this study adds much to the studies that have already been done".   I would so, it does''t add anything.
Nathan Goodyear

Short-term testosterone therapy failed to increase CV risk in women | Endocrinology - 0 views

www.healio.com/...d-to-increase-cv-risk-in-women

testosterone therapy women female hormone hormones cardiovascular disease

shared by Nathan Goodyear on 23 May 14 - No Cached
  • Nathan Goodyear on 23 May 14
     
    24 week study of 71 women post-hysterectomy finds no increase in cardiovascular biomarkers.  Several problems with this study.  First, there was a large drop out--24%.  Second and most important, the women were pretreated with estrogen prior to Testosterone therapies were initiated.  Other studies have proposed that this protects cardiovascular risk in women on Testosterone.  Previous studies show increasing endogenous Testosterone is associated with increasing cardiovascular disease in women.   This study would be much better if no estradiol was prescribed.  That would give an unbiased view of Testosterone in post-hysterectomy women.  Not much can be taken from this study. If you doctor doesn't know this, find another doctor.  Inherent bias in this study as ties to the manufacturer of the Testosterone was disclosed. This study point to the inherent flaws in so much of the medical literature today.  Most would read the headlines and read no further, but the "further" dispels the headline as flawed.
Nathan Goodyear

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

circ.ahajournals.org/...1242.full

CVD cardiovascular disease SHBG free androgen index hormone hormones women perimenopause

shared by Nathan Goodyear on 28 Oct 14 - No Cached
  • Nathan Goodyear on 28 Oct 14
     
    The opposite effect strikes again: elevated free androgen index is associated with CV risk in perimenopause women across 5 ethnic groups.  Low SHBG was associated with increased CVD.
Nathan Goodyear

'Mediterranean' dietary pattern for the primary prevention of cardiovascular disease. -... - 0 views

www.ncbi.nlm.nih.gov/...23939686

CVD cardiovascular disease mediterranean diet nutrition diet

shared by Nathan Goodyear on 27 Oct 15 - No Cached
  • Nathan Goodyear on 27 Oct 15
     
    Mediterranean diet found to reduce CV risk.  
Nathan Goodyear

Low serum testosterone and increased mortality in men with coronary heart disease -- Ma... - 0 views

heart.bmj.com/...1821.full.html

low T low T testosterone mortality men CV CVD cardiovascular heart heart disease male

shared by Nathan Goodyear on 10 Nov 12 - No Cached
  • Nathan Goodyear on 10 Nov 12
     
    low serum testosterone associated with increased mortality in men with coronary disease. This study used "bio-available" testosterone and total testosterone.
Nathan Goodyear

Normalization of testosterone level is associated with reduced incidence of myocardial ... - 0 views

eurheartj.oxfordjournals.org/...eurheartj.ehv346

low T low Testosterone men Testosterone mortality stroke MI CVD cardiovascular disease hormones male

shared by Nathan Goodyear on 11 Aug 15 - No Cached
  • Normalized-TRT group had significantly fewer deaths than no-TRT
  • Mortality was also significantly lower in the non-normalized-TRT group compared with those in no-TRT group
  • the normalized-TRT group was associated with significantly increased all-cause mortality-free survival (log-rank, P < 0.05) compared with the non-normalized-TRT or no-TRT groups
  • ...10 more annotations...
  • normalized-TRT group showed lower risk of MI than non-normalized-TRT (HR: 0.82, CI 0.71–0.95, P = 0.008) and no-TRT
  • normalized-TRT group had significantly lower stroke events compared with non-normalized-TRT (HR: 0.70, CI 0.51–0.96, P = 0.028) and no-TRT
  • study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes
  • retrospective study
  • the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the TT levels
  • Patients who failed to achieve the therapeutic range after TRT did not see a reduction in MI or stroke and had significantly less benefit on mortality
  • selected patients without any previous history of MI or stroke prior to initiation of TRT to reduce bias related to CV outcomes
  • currently only half of the men on TRT had been diagnosed with hypogonadism.
  • 25% of users did not have their T concentrations tested prior to initiating therapy, and 21% of those prescribed TRT did not have their levels tested at any time during treatment.
  • men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
  • Nathan Goodyear on 11 Aug 15
     
    Testosterone therapy in men with low T found to reduce all cause mortality, stroke and MI.
Nathan Goodyear

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views

jme.endocrinology-journals.org/...R51.full

metabolic endotoxemia obesity insulin resistance cardiovascular disease LPS inflammation

shared by Nathan Goodyear on 04 Aug 14 - No Cached
  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
  • ...37 more annotations...
  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
  • dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
  • it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
  • this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
  • LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
  • When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
  • It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
  • Nathan Goodyear on 04 Aug 14
     
    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

Normalization of testosterone level is associated with reduced incidence of myocardial ... - 0 views

eurheartj.oxfordjournals.org/...2706

low T low Testosterone Testosterone Testosterone therapy mortality MI stroke heart men male hormones

shared by Nathan Goodyear on 18 Jan 16 - No Cached
  • In this study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes.
  • retrospective study
  • significant benefit is observed only if the dose is adequate to normalize the TT levels
  • ...9 more annotations...
  • the mechanisms for these effects remain speculative
  • It can be postulated that the beneficial effect of normal T levels on adipose tissue, insulin sensitivity, and lipid profiles or by its anti-inflammatory and anticoagulant properties, as reported by other investigators, might have contributed to our findings
  • off-label use of TRT remains a concern
  • Recent FDA analyses suggest that currently only half of the men on TRT had been diagnosed with hypogonadism
  • 25% of users did not have their T concentrations tested prior to initiating therapy
  • 21% of those prescribed TRT did not have their levels tested at any time during treatment
  • two very recent meta-analyses suggested a lack of convincing evidence posed by TRT.
  • men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
  • TRT should aim for doses resulting in normalization of TT level as this was shown to be associated with reduction in adverse CV events
  • Nathan Goodyear on 18 Jan 16
     
    Testosterone therapy in men with low T to restore physiologic Testosterone levels found to reduce mortality, MI, and stroke risk.
Nathan Goodyear

Endothelium and control of vascular function. State of the Art lecture. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...2661425

vitamin C NO nitric oxide blood pressure CV cardiovascular disease hypertension endothelium

shared by Nathan Goodyear on 20 Dec 17 - No Cached
  • Nathan Goodyear on 20 Dec 17
     
    vitamin C, absorbed via the endothelium, increases NO.  This will have a positive effect in lowering the blood pressure.
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