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Nathan Goodyear

Access : Impact of the association between elevated oestradiol and low testosterone lev... - 0 views

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    low T and elevated E2 result in ED in men.  The authors conclude that E2 provides an additive effect on that of low T.  Yet, they fail to realize the previous research that high aromatase activity (Testosterone to Estradiol production) causes the low T.
Nathan Goodyear

Response to Media Reports Associating Testosterone Treatment with Greater Heart Attack ... - 0 views

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    Life extesnsions rebuttal to recent JAMA study.  There was several significant flaws in that study and thus limited evidence can be gained by that study.  In fact, I find no useful clinical information from that study. In the rebuttal, there are flaws. The reference the low serum T after treatment and correctly discuss aromatase activity.  But they fail the mention that the less than optimal serum T is likely the result of the high aromatase activity in these men.  Age, stress, and weight are primary causes of increases estrogen production in these men.  These would be why likely high estrogen production occurred and less than optimal serum T resulted.   And, increased E2 will cause an increase in CRP which can precipitate CVD events.
Nathan Goodyear

Evaluation of the hypothalamic-pituitary-gonadal a... [Andrology. 2013] - PubMed - NCBI - 0 views

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    Increasing glucose levels associated with declining LH pulses in men with type II diabetes.  This is one proposed mechanism for low T in men.  There has been great debate about if Low T was in part the cause of Diabetes or an effect of diabetes.  This proposes that low T is due to a decreased LH pulse as a result of rising glucose.
Nathan Goodyear

Prevalence and Correlates of Late-Onset Hypogonadism Among Korean Men Aged 40 Years or ... - 0 views

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    Study of Korean men finds late onset of hypogonadism to be 16.8% in their study of 1,235 men older than 40.  This is a higher rate than other studies, but lower than others (38.7% in American men).  The test definition of low T was set at 3.2 ng/ml.  Abdominal obesity, metabolic syndrome, diabetes, and increasing age were associated with low T. Low T is clearly not a problem unique to America.  It definitely appears that a decreasing Testosterone level is a marker of poor health in men.  
Nathan Goodyear

Late onset hypogonadism of men is not equivalent t... [Maturitas. 2014] - PubMed - NCBI - 0 views

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    published ahead of print, so full article is not available.  Abstract points to low T as a result of metabolic factors i.e. obesity, inflammation...This is true.  The authors, in the abstract, point to the differences in Menopause in women versus low T in men.  
Nathan Goodyear

Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evide... - 0 views

  • Circulating testosterone (T) in men declines progressively by 0.4–2% per year from the third decade onward
  • late-onset hypogonadism (LOH) (6, 7), whereas others have used various terms including andropause, male menopause, and androgen deficiency syndrome of the aging male.
    • Nathan Goodyear
       
      all names for Low T--interesting
  • Secondary hypogonadism is associated with obesity (and potentially reversible) independently of age
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  • primary hypogonadism (probably the genuine form of LOH) is strongly associated with age
  • Compensated hypogonadism represents a distinct clinical entity that warrants continued monitoring to prevent or preempt further deterioration
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    Study divides low T into primary (age), secondary (weight), and compensated hypogonadism (elevated LH with normal T)
Nathan Goodyear

Erectile dysfunction and testosterone deficiency. - PubMed - NCBI - 0 views

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    A high percentage of men that fail PDE5 therapy have low T and the addition of T therapy improves the effects of PDE5 therapy.  T provides a positive impact on NO synthase which increased NO, which PDE5 therapies must have to work.
Nathan Goodyear

Immune responses to malignancies - 0 views

  • increased densities of T-cell infiltrates with a high proportion of CD8+ T cells within primary colorectal carcinomas were associated with a significant protection against tumor recurrence
  • coexpression of genes mediating cytotoxicity and TH1 adaptive immune responses accurately predicted survival in patients with colorectal carcinoma independently of the metastatic status.
  • tumor-specific cytolytic T lymphocytes (CTLs)
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  • tumor-associated antigens (TAs)
  • Proinflammatory cytokines secreted by inflammatory cells can contribute to tumor progression, and soluble factors produced by the tumor in response to nonspecific or tumor-specific signals, such as prostaglandin E2 (PGE2), adenosine, or TGF-β, downregulate functions of immune cells
  • they are largely ineffective in arresting tumor growth, although they can proliferate and mediate antitumor cytotoxicity on their removal from the tumor bed and ex vivo IL-2 activation.42
  • DCs (HLA-DR+CD86+CD80+CD14−) are nature’s best APCs
  • They are a common component of tumor immune infiltrates and are responsible for the uptake, processing, and cross-presentation of TAs to naive or memory T cells, thus playing a crucial role in the generation of tumor-specific effector T cells
  • DCs control the induction of Treg cells. In patients with cancer, cellular interactions between antigen-presenting DCs and T cells lead to expansion and accumulation of Treg cells at the tumor site and in the periphery
  • NK cells (CD3−CD56+CD16+), which mediate innate immunity and contain both perforin-rich and granzyme-rich granules, are well equipped to mediate lysis of tumor cells
  • B cells (CD19+, CD20+) are also rare in most human tumors, with the exception of breast cancer and melanoma
  • The initial acute inflammation involving the recruitment and influx of antitumor effector cells is replaced by chronic inflammation in later stages of tumor progression
  • Tissue hypoxia plays a major role in shaping the nature of immune infiltrates in tumors
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    Another great review of the immune system during different stages of carcinogenesis; how the cancer manipulates the immue system to cloak itself from the immune system.
Nathan Goodyear

Evidence for hypogonadism in massively obese ... [Horm Metab Res. 1981] - PubMed - NCBI - 0 views

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    In obese men, low T is the result of increased estradiol formation from aromatase activity.  Low SHBG is no enough to offset the decrease in free T levels.
Nathan Goodyear

The Complex Role of Estrogens in Inflammation - 0 views

  • These studies suggest inflammation-dependent up-regulation of ERβ relative to ERα.
  • up-regulation of ERβ relative to ERα under hypoxic conditions, which might lead to a preponderance of signaling through ERβ pathways
  • it seems that E2 at periovulatory to pregnancy levels inhibited proinflammatory cytokines from PBMCs
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  • it is clear that E2 can stimulate antibody production by B cells, probably by inhibiting T cell suppression of B cells
  • In cycling women, the largest quantities of Ig were detected before ovulation
  • In contrast, E2 at high concentrations leads to a suppression of B-lymphocyte lineage precursors
  • E2 at periovulatory to pregnancy serum levels is able to stimulate antibody secretion under healthy conditions but also in autoimmune diseases, whereas similar serum levels of E2 lead to a suppression of bone marrow B cell lineage precursors
  • In chronic inflammatory disorders, where B cells play a decisive role, E2 would promote the disease when autoaggressive B cells are already present, whereas chronically elevated E2 would inhibit initiation of an autoimmune disease when no such B cells are available. This might be a good reason why particularly B cell-dependent diseases such as SLE, mixed connective tissue disease (Sharp syndrome), IgA nephropathy, dermatitis herpetiformis, gluten sensitive enteropathy, myasthenia gravis, and thyroiditis appear in women in the reproductive years, predominantly, in the third or fourth decades of life
  • Th17 cells are thought to be the main responsible cells for chronic inflammatory tissue destruction in autoimmune diseases
  • IFN-γ, IL-12, and TNF were allocated to Th1 reactions
  • IL-4, IL-5, and IL-10 to Th2 responses
  • antiinflammatory T regulatory cells producing TGF-β and proinflammatory T helper type 17 cells (Th17) producing IL-17
  • no direct effects of estrogens on Th17 cells or IL-17 secretion have been described until now.
  • So-called Th17 cells producing IL-17 are the main T cells responsible for chronic inflammation.
  • Because IFN-γ has been allocated a Th17-inhibiting role (Fig. 1⇑), its increase by E2 at pregnancy doses and the E2-mediated inhibition of TNF must be viewed as a favorable effect in chronic inflammation
  • in humans and mice, E2 at periovulatory to pregnancy levels stimulates IL-4, IL-10, and IFN-γ but inhibits TNF from CD4+ T cells
  • In humans and mice, E3 and E2, respectively, at pregnancy levels inhibit T cell-dependent delayed type hypersensitivity
  • increased IL-4, IL-10, and IFN-γ in the presence of low TNF support an antiaggressive immune response
  • secretion of IL-1β is increased at periovulatory/proestrus to early pregnancy levels, whereas IL-1 secretion is inhibited at high pregnancy levels
  • The dichotomous effect of E2 on IL-1β and TNF at high and low concentrations is most probably due to inhibition of NF-κB at high concentrations
  • experiments with mouse and rat macroglial and microglial cells demonstrate that E2 at proestrus to pregnancy levels exerts neuroprotective effects by increasing TGF-β and by inhibiting iNOS and NO release, and reducing expression of proinflammatory cytokines and prostaglandin E2 production.
  • E2 at periovulatory to pregnancy levels inhibits NF-κB activation, which must be viewed as an antiinflammatory signal
  • It was shown that E2 concentrations equal to or above 10−10 m are necessary to inhibit NF-κB activation
  • important proinflammatory cytokines are typically inhibited at periovulatory (proestrus) to pregnancy levels of E2, which is evident for IL-6, IL-8, and TNF
  • low E2 concentrations were demonstrated to have no or even stimulatory effects
  • This renders a woman in the postmenopausal phase to a more proinflammatory situation
  • most in vitro studies demonstrated a stimulatory effect of E2 on secretion of IL-4, IL-10, and TGF-β typically at periovulatory to pregnancy levels
  • E2 at periovulatory to pregnancy levels has an ameliorating effect on chronic inflammatory diseases as long as B cell-dependent immunity or an overshooting fibrotic tissue repair process do not play a crucial pathogenic role. However, when the B cell plays an important role, E2 might even stimulate the disease process as substantiated by flare-ups in SLE during pregnancy
    • Nathan Goodyear
       
      SLE, mixed connective tissue disease (Sharp syndrome), IgA nephropathy, dermatitis herpetiformis, gluten sensitive enteropathy, myasthenia gravis, and thyroiditis
  • Short-term administration of E2 at pregnancy levels was shown to induce an inflammatory response specific to the lateral prostate of the castrated male rat
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    great review of the complex interaction between Estrogens and inflammation.  Reference here is in females.
Nathan Goodyear

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

  • 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
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  • 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
       
      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
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    to be read
Nathan Goodyear

Hormonal changes and their impact on cognition and... [Maturitas. 2014] - PubMed - NCBI - 0 views

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    low T appears to be associated with cognitive decline in men.  If low T is present on testing, then therapy is appropriate to improve cognition.
Nathan Goodyear

Systematic literature review of the risk factors, ... [Andrology. 2014] - PubMed - NCBI - 0 views

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    10 year Cochrane review finds low T associated with aging, obesity, MetS, and poor health.  The authors suggest that low T "may be linked to earlier all-cause and cardiovascular related mortality among men".  This is supported by other studies.  Only abstract available here.
Nathan Goodyear

Wasting syndrome with deep bradycardia as ... [BMC Endocr Disord. 2014] - PubMed - NCBI - 0 views

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    long standing low T linked to bradycardia and heart failure in case series.  Exact relationship of cause/effect unknown, though low T has been shown to be associated with wide spectrum of increased risk of CVD.
Nathan Goodyear

Hypogonadal Symptoms Are Associated With Different S... [Urology. 2014] - PubMed - NCBI - 0 views

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    This study looked at Total Testosterone and prevalence of low T symptoms.  As the authors stated, increased prevalence was found between 320 and 375 ng/dl.  Whereas, < 300 ng/dl was consistent with predictable low T symptoms.  It would have be more thorough if they had looked at salivary Testosterone levels and bioavailable as well.
Nathan Goodyear

Elderly men over 65 years of age with late-onset hypogonadism benefit as much from test... - 0 views

  • The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins.
  • obesity, but also impaired general health, are the more common causes of low testosterone in aging men
  • Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality,
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  • advanced age, obesity, a diagnosis of metabolic syndrome, and poor general health status were predictors of LOH
  • Diabetes mellitus was correlated with hypogonadism in most studies
  • coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with the incidence of low testosterone
  • LOH can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol/L (3.2 ng/mL) and a free testosterone level of less than 220 pmol/L (64 pg/mL)
    • Nathan Goodyear
       
      the European Male Aging study defined low T as total < 320 ng/dl and free < 64 pg/ml.  
  • Mean weight decreased
  • Waist circumference decreased
  • Total cholesterol decreased
  • Low-density lipoprotein decreased
  • Triglycerides decreased
  • High-density lipoprotein (HDL) increased
  • ratio of total cholesterol to HDL improved
  • Prostate volume increased
  • PSA increased
  • The benefits for men older than 65 years of age were compared with those of younger men, and the improvements in body weight, metabolic factors, psychological functioning, and sexual functioning were of the same magnitude in both age groups
  • weight loss was progressive over the 6-year period, effects of testosterone on lipids and on psychological and sexual functioning reached a plateau after approximately 3 years and these effects were sustained
  • Effects of testosterone on hematopoiesis, on the prostate, and on bladder function were not more severe in older men than in younger men
  • observe a mild increase in prostate volume and serum PSA over time, which is a normal finding in aging men. Maybe somewhat surprising, postvoiding residue and the IPSS did not deteriorate with aging but showed a degree of improvement
  • the severity of the metabolic syndrome is associated with the severity of lower urinary tract symptoms
  • The symptoms of the metabolic syndrome improve upon testosterone treatment and testosterone may thus have a favorable effect on lower urinary tract symptoms
  • it seems reasonable to conclude that the risks of testosterone administration to elderly men are not disproportionately higher in elderly men than in younger men.
  • Despite evidence to the contrary, physicians still harbor a wrongful association between testosterone and the development of prostate pathology (prostate cancer and benign prostate hyperplasia)
  • Not surprisingly, the incidence of prostate cancer was higher in older men; however, it was lower than expected in both groups
  • These observations suggest that the incidence of prostate cancer in patients receiving testosterone therapy, both in the younger and in the older group, was not greater than in the general population not receiving testosterone treatment
  • The historical fear that raising testosterone levels will result in more prostate cancer has been dispelled, particularly by the work of Abraham Morgentaler
  • Higher serum testosterone levels fail to show an increased risk of prostate cancer, and supraphysiological testosterone does not increase prostate volume or PSA in healthy men
  • This apparent paradox is explained by the "saturation model,"
  • Recent studies indicate no increased risk of prostate cancer among men with serum testosterone in the therapeutic range
  • In the present observational study, no cases of major adverse cardiovascular events occurred.
  • the benefits of testosterone therapy are fully achieved only by long-term treatment
  • To achieve maximal benefits, good patient adherence is a prerequisite
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    Study finds new difference in Testosterone benefits and/or side effects between men < 65 with low T and men > 65 with low T.
Nathan Goodyear

Testosterone Substitution Normalizes Elevated Serum Leptin Levels in Hypogonadal Men: T... - 0 views

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    Men with low T and elevated Leptin, have Leptin normalized with Testosterone therapy.  In obese men, Leptin is inversely associated with Testosterone.  This points to more cause/effect relationship with low T, elevated Leptin, and obesity in men.
Nathan Goodyear

Age, Insulin Requirements, Waist Circumference, and Triglycerides P... - PubMed - NCBI - 0 views

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    Study looked at low T in men with type 1 Diabetes.  Only abstract available here.  Study finds appx 10% prevalence with age, waist circumference and insulin requirements as predictive of low T in men with type 1 Diabetes.
Nathan Goodyear

The Association between Premature Coronary Art... [Arch Iran Med. 2014] - PubMed - NCBI - 0 views

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    Low free and Total Testosterone levels found to be associated with premature CAD in men.  Some confounders were present, which they tried to account for--this should leave some healthy questioning of this study results.  That being said, this is not the first time low T has been found to be associated with CAD in men.  This study found a statistical significant association with Free and Total Testosterone levels in young men.  Another point to consider is the Low T a cause or a biomarker and an effect of poor/declining health?  I would so more to the biomarker point.
Nathan Goodyear

The relationship between testosterone, metabolic syndrome, and mean carotid intima-medi... - 0 views

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    Low Testosterone is associated with increased IMT.  Low T is associated with Mets.  MetS is associated with low T.  MetS is associated with increased IMT.
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