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Nathan Goodyear

Androgen Deprivation Therapy, Insulin Resistance, and Cardiovascular Mortality: An Inconvenient Truth - Basaria - 2013 - Journal of Andrology - Wiley Online Library - 0 views

onlinelibrary.wiley.com/...full

androgen deprivation therapy androgen male men hormone hormones deprivation therapy prostate cancer cardiovascular disease insulin resistance diabetes metabolic syndrome mortality CVD

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    Androgen deprivation therapy is associated with increased diabetes, metabolic syndrome, insulin resistance, and cardiovascular mortality.  The longer the duration of therapy, the more the progression of metabolic dysfunction.  This process seems similar to chemotherapy i.e. secondary cancer due to chemotherapy.  The treatment of one disease, prostate cancer in this case, leads to an increase in the risk of the #1 killer in men--logic seems severely flawed there.
Nathan Goodyear

More about plasma renin and cardiovascular mortality - 0 views

eurheartj.oxfordjournals.org/...eurheartj.ehr187.extract

plasma renin cardiovascular disease mortality hypertension

shared by Nathan Goodyear on 08 Sep 11 - No Cached
  • Nathan Goodyear on 08 Sep 11
     
    plasma renin and cardiovascular disease and mortality.
Nathan Goodyear

Metabolic syndrome, testosterone, and cardiovascular mortality in men. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21676188

low T low Testosterone bioavailable Testosterone cardiovascular disease metabolic syndrome mortality men male hormone hormones

shared by Nathan Goodyear on 04 Mar 15 - No Cached
  • Nathan Goodyear on 04 Mar 15
     
    study of 596 men finds that lower bioavailable Testosterone in those men with Metabolic Syndrome, have an increased cardiovascular mortality in those > 40.
Nathan Goodyear

Effect of selenium and Q10 on the cardiac biomarker NT-proBNP: Scandinavian Cardiovascular Journal: Vol 47, No 5 - 0 views

www.tandfonline.com/...14017431.2013.820838

CoQ10 Selenium cardiovascular disease mortality NT-proBNP cardiovascular heart health

shared by Nathan Goodyear on 11 Apr 17 - No Cached
  • Nathan Goodyear on 11 Apr 17
     
    4 year study finds that 200 mg CoQ10 and 200 mg Se reduced NT-proBNP and cardiovascular mortality.  
Nathan Goodyear

Sex steroids and cardiovascular disease Yeap BB - Asian J Androl - 0 views

www.ajandrology.com/article.asp

cardiovascular disease CVD sex estradiol carotid intima-media thickness hormones hormone men Testosterone estrogen

shared by Nathan Goodyear on 15 Jan 14 - No Cached
  • Levels of SHBG are higher in older men, therefore levels of free T decline more steeply than total T as men's age increases.
  • calculations based on mass action equations may not reflect precisely free T measured using a reference method
  • free T declines more steeply with age than total T in both cross-sectional [35] and longitudinal studies, [36] as does free E2 in comparison to total E2
  • ...22 more annotations...
  • T may slow development of or progression of atherosclerosis by modulating effects on insulin resistance, inflammation, endothelial function, preclinical atherosclerosis or the vasculature.
  • these cross-sectional and longitudinal studies support a relationship between low circulating T with CIMT and higher E2 with its progression
  • lower levels of T are biomarkers for aortic vascular disease
  • circulating free T was negatively associated with the presence of AAA
  • luteinizing hormone (LH) was positively associated.
  • low levels of total or bioavailable T were associated with aortic atherosclerosis manifested as calcified deposits detected by radiography
  • Men with total or free T in the lowest quartile had increased adjusted ORs for PAD defined as ABI <0.90, as did men with free E2 in the highest quartile of values
  • The apparent association of SHBG with intermittent claudication reflects the correlation of total T with SHBG, while the contribution of E2 to risk of PAD remains unclear
  • men with total T in the lowest quartile of values (<11.7 nmol l−1 ) experienced an increased incidence of stroke or transient ischemic attack
  • lower total T with increased incidence of CVD events
  • cohort studies in mostly older men have supported the association of lower androgen levels with higher mortality
  • lower total or free T levels were associated with mortality in older men, but with discordant results for cause-specific mortality and for associations of E2
  • several large studies identifying lower endogenous levels of total or free T as independent predictors of all-cause or CVD-related deaths in middle-aged and older men
  • T exhibits anti-inflammatory effects, enhances flow-mediated brachial artery reactivity, and reduces arterial stiffness
  • Short-term T therapy had a beneficial effect on exercise-induced myocardial ischemia in middle-aged men with coronary artery disease or chronic stable angina, [95],[96],[97] and reduced angina frequency in older men with diabetes and coronary artery disease
  • T therapy resulted in an increase in treadmill test duration and time to ST segment depression
  • there are interventional studies supporting a protective effect of exogenous T against myocardial ischemia in men with coronary artery disease
  • employ conservative doses
    • Nathan Goodyear
      Nathan Goodyear on 16 Jan 14
       
      This dosing is 100 fold higher then peak production of a  young man at 20-22.
  • Observational studies indicate that lower levels of endogenous T in older men are associated with the presence of carotid atherosclerosis, aortic and peripheral vascular disease, and incidence of CVD events and mortality
  • Interventional studies have shown beneficial effects of exogenous T on vascular function and on exercise-induced myocardial ischemia in men with coronary artery disease
    • Nathan Goodyear
      Nathan Goodyear on 16 Jan 14
       
      the therapies employed in these studies were massively overdosed.
  • Nathan Goodyear on 15 Jan 14
     
    Nice review of all the sex hormones and their relationship to CVD in men.  
Nathan Goodyear

Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis - 0 views

jcem.endojournals.org/...3007.full

cardiovascular mortality low Testosterone T free bioavailable

shared by Nathan Goodyear on 21 Nov 13 - No Cached
  • Nathan Goodyear on 21 Nov 13
     
    low bioavailable "endogenous" Testosterone associated with increased cardiovascular mortality.
Nathan Goodyear

Thyroid Function Tests and Mortality in Aged Hospitalized Patients: A 7-Year Prospective Observational Study - 0 views

jcem.endojournals.org/...4683.abstract

free T3 fT3 hypothyroid hypothyroidism T3 mortality cardiovascular disease thyroid function

shared by Nathan Goodyear on 11 Dec 13 - No Cached
  • Nathan Goodyear on 11 Dec 13
     
    Here is an interesting finding:  low free T3 is significantly associated with increased cardiovascular and all-cause mortality in 7 prospective study on hospitalized patients.
Nathan Goodyear

Blood lead levels and mortality. [Arch Intern Med. 2002] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...12437403

Pb lead cardiovascular disease CVD heart health mortality

shared by Nathan Goodyear on 16 Sep 14 - No Cached
  • Nathan Goodyear on 16 Sep 14
     
    Lead exposure associated with increased cardiovascular disease and mortality.
Nathan Goodyear

Testosterone, Dihydrotestosterone and Incident Cardiovascular Disease and Mortality in the Cardiovascular Health Study: The Journal of Clinical Endocrinology & Metabolism: Vol 0, No 0 - 0 views

press.endocrine.org/...jc.2013-3576

low Testosterone T DHT men's health DihydroTestosterone CVD cardiovascular disease mortality men male hormone hormones health

shared by Nathan Goodyear on 24 Mar 14 - No Cached
  • Nathan Goodyear on 24 Mar 14
     
    Abstract published ahead of print finds that DHT and calculated free DHT was associated with CVD and all-cause mortality.  This cohort found that Total Testosterone and calculated free Testosterone were not.  
Nathan Goodyear

Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies | European Heart Journal | Oxford Academic - 0 views

academic.oup.com/...ehx163

HDL cholesterol cardiovascular disease mortality

shared by Nathan Goodyear on 30 Aug 17 - No Cached
  • Nathan Goodyear on 30 Aug 17
     
    High HDL found to actually increase cardiovascular risk in men and women. Peak benefit is found at 58 mg/dl and 77 mg/dl for men and women respectively. Higher levels of HDL >90 increased risk and all-cause mortality in men and women.
Nathan Goodyear

Beyond the male sex hormone: deciphering the metabolic and vascular actions of testosterone - 0 views

joe.endocrinology-journals.org/...C1.full

AR androgen receptors androgen receptor testosterone androgen receptors Diabetes metabolic syndrome MetS CVD cardiovascular disease men hormone hormones male

shared by Nathan Goodyear on 08 May 13 - No Cached
  • androgen deprivation therapy results in unfavorable changes in body composition, insulin resistance, and dyslipidemia and predisposes men to develop atherosclerosis and an increased risk of cardiovascular mortality
  • The hypogonadal–obesity cycle hypothesis was originally proposed by Cohen in 1999 to explain the relationship between low testosterone levels and metabolic disease. It was based on the finding that obesity impairs testosterone levels by increasing the aromatization of testosterone to estradiol, while low testosterone levels promote increased fat deposition
  • adipocytokines contribute to low testosterone levels as well as to the processes underlying metabolic syndromes and type 2 diabetes
  • ...15 more annotations...
  • hypogonadal–obesity–adipocytokine hypothesis
  • The presence of estradiol and the adipocytokines TNF-α, IL6, and leptin (as a result of leptin resistance in obesity) inhibits the hypothalamic–pituitary–testicular axis response to decreasing androgen levels
  • An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen research
  • As early as the 1940s, the therapeutic use of testosterone was reported to improve angina pectoris in men with coronary artery disease
  • most of the epidemiological studies reported increased cardiovascular risk and mortality in men with low testosterone levels
  • long-term testosterone replacement appears to be a safe and effective means of treating hypogonadal elderly men
  • a recent interventional trial showed that testosterone treatment was associated with decreased mortality when compared with no testosterone treatment in an observational cohort of men with low testosterone levels
  • a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular risk
  • The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent and -independent vasodilatory effects
  • Endothelial-dependent actions of testosterone increase the expression or activity of endothelial nitric oxide synthase and enhance nitric oxide production, which in turn activates cyclic guanosine monophosphate to induce vasorelaxation in smooth muscle cells
  • Endothelial-independent mechanisms of testosterone are believed to occur primarily via inhibition of voltage-operated Ca2+ channels and/or activation of K+ channels in smooth muscle cells
  • Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
  • testosterone has demonstrated anti-inflammatory effects to protect against atherogenesis in animal studies
  • both genomic AR activation to modulate gene transcription and non-genomic activation to modulate the rapid intracellular signaling pathways of ion channels may mediate testosterone effects on vascular function and inflammation.
  • Butenandt & Ruzicka first showed how testosterone is synthesized and responsible for masculine characteristics in the early 1930s
  • Nathan Goodyear on 08 May 13
     
    Awesome review on the current understanding of Testosterone and Diabetes, metabolic syndrome, and CVD.  This article even goes into the literature on androgen receptors.
Nathan Goodyear

Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study - The Lancet - 0 views

www.thelancet.com/...fulltext

hand-grip strength test hand-grip hand-grip strength mortality CVD cardiovascular disease cardiovascular strength grip

shared by Nathan Goodyear on 21 Jun 16 - No Cached
  • Nathan Goodyear on 21 Jun 16
     
    hand grip strength found to be strong predictor of all-cause and cardiovascular mortality.  Even higher than systolic blood pressure.
Nathan Goodyear

DHEA-S Levels and Cardiovascular Disease Mortality in Postmenopausal Women: Results from the National Institutes of Health-National Heart, Lung, and Blood Institute (NHLBI)-Sponsored Women's Ischemia Syndrome Evaluation (WISE) - 0 views

jcem.endojournals.org/...4985.abstract

cardiovascular dhea postmenopausal women

shared by Nathan Goodyear on 31 May 11 - No Cached
  • Nathan Goodyear on 31 May 11
     
    Low DHEA in postmenopausal women linked to increased risk of mortality, especially Cardiovascular
Nathan Goodyear

Testosterone level in men with type 2 diabetes mellitus and related metabolic effects: A review of current evidence - 0 views

www.ncbi.nlm.nih.gov/...PMC4364844

low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome

shared by Nathan Goodyear on 30 Mar 15 - No Cached
  • defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
  • the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
  • most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equals 251 to 366 in serum Total Testosterone
  • ...57 more annotations...
  • Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
  • −0.124 nmol/L/year in serum total testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equates to a 4 ng/dl decline annually in total Testosterone.
  • In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
  • In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
  • testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
  • by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
  • testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
  • In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
  • independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
  • In short, androgen improves insulin resistance by changing body composition and reducing body fat.
  • Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
  • In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
  • leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
  • Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      So what is "unequivocal"?
  • Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
  • 30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
  • As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
  • Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
  • alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
  • listed in Table​T
  • A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
  • Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
  • subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
  • In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
  • Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
  • Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
  • The reduction of total testosterone was 0.4% per year in both groups
  • HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
  • pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
  • In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
  • Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
  • Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
  • The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
  • In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
  • a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
  • In India, men with CAG ≤19 had increased risk of prostate cancer
  • the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
  • assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
  • In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
  • a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
  • A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
  • Low testosterone is commonly associated with a high prevalence of MES
  • most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
  • MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
  • Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
  • In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
  • weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
  • To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
  • In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
  • low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
  • Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
  • low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
  • low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
  • European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
  • Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
  • serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
  • Nathan Goodyear on 30 Mar 15
     
    Nice review of Testosterone levels and some of the evidence linking Diabetes with low T.  However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling.  The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
Nathan Goodyear

Cardiovascular disease in Europe: epidemiological update 2016 | European Heart Journal | Oxford Academic - 0 views

academic.oup.com/...2536403

cardiovascular disease cancer mortality europe

shared by Nathan Goodyear on 10 Apr 18 - No Cached
  • Nathan Goodyear on 10 Apr 18
     
    Cancer will soon overtake cardiovascular disease as the #1 cause of mortality in the US and worldwide as happened in 12 European countries. The current dogma for cancer treatment is not working; the goal must be prevention. The 12 countries include: Spain, France, Belgium, Denmark, Italy, Israel, Luxembourg, The Netherlands, Norway, Portugal, Slovenia, and UK.
Nathan Goodyear

Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men - 0 views

circ.ahajournals.org/...2694.full

testosterone cardiovascular disease Cancer prostate

shared by Nathan Goodyear on 17 Aug 11 - No Cached
  • Nathan Goodyear on 17 Aug 11
     
    High endogenous Testosterone levels in men found to equal low cardiovascular and prostate risk.  Low Testosterone increased cardiovascular risk
Nathan Goodyear

Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study -- Sgarbi et al. 162 (3): 569 -- European Journal of Endocrinology - 0 views

www.eje-online.org/...569

subclinical thyroid dysfunctions

shared by Nathan Goodyear on 24 Mar 11 - No Cached
  • subclinical hyperthyroidism is an independent risk factor for all-cause and cardiovascular mortality, while subclinical hypothyroidism is associated with all-cause mortality
  • Nathan Goodyear on 24 Mar 11
     
    sub-clinical hypothyroidism and sub-clinical hyperthyroidism associated with increased mortality
Nathan Goodyear

Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease - NEJM - 0 views

www.nejm.org/...NEJM199707243370403

homocysteine mortality cardiovascular disease CAD risk

shared by Nathan Goodyear on 03 Aug 11 - No Cached
  • Plasma total homocysteine levels are a strong predictor of mortality in patients with angiographically confirmed coronary artery disease
  • Nathan Goodyear on 03 Aug 11
     
    elevated homocysteine strong predictor of mortality
Nathan Goodyear

Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men - 0 views

circ.ahajournals.org/...2694.abstract

testosterone low mortality cardiovascular disease CVD T

shared by Nathan Goodyear on 26 Apr 12 - No Cached
  • Nathan Goodyear on 26 Apr 12
     
    low Testosterone found to be inversely correlated to an increase in CVD and mortality.
Nathan Goodyear

Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction - NEJM - 0 views

www.nejm.org/...NEJMoa055227

NORVIT trial homocysteine vitamin B12 B6 folic acid CVD cardiovascular disease MI stroke strokes events

shared by Nathan Goodyear on 25 Jul 12 - No Cached
  • Nathan Goodyear on 25 Jul 12
     
    NORVIT trial showed that vitamin B12, B6, and folic acid reduced homocysteine levels by 27%, however it did not lower MI, stroke,or mortality rate.  ONe variable to consider is the polypharmacy of the study group ie.  they were taking statins, beta blockers, diuretics, coumadin... so was the lack of change in mortality the result of polypharmacy?  And was the polypharmacy blocking the increased CVD risks associated with elevated homocysteine that would have been treatable with vitamin B12, B6, and folic acid.
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