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Nathan Goodyear

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study: The Journal of Clinical Endocrinology & Metabolism: Vol 87, No 2 - 0 views

press.endocrine.org/...jcem.87.2.8201

low T Testosterone low T low Testosterone male men hormone hormones DHT aging BMI MMAS Massachusetts Male Aging Study

shared by Nathan Goodyear on 11 Aug 14 - No Cached
  • Nathan Goodyear on 11 Aug 14
     
    MMAS study finds an age associated decline in Total Testosterone and free Testosterone levels. This study focus on the % decline based on other variables i.e. age, BMI...IN contrast, a 3.5% rise in DHT levels were observed. There is debate about the correlation of serum DHT and intra-tissue DHT. In fact, studies suggest there is little correlation.
Nathan Goodyear

Urinary estrogen metabolites in women at high risk for breast cancer - 0 views

carcin.oxfordjournals.org/...1532.full

breast cancer CA estrogen metabolism 2:16 OHE 2-OH-estrone 16-alpha-OH-estrone

shared by Nathan Goodyear on 10 May 12 - No Cached
  • obesity has also been linked to preferential estrogen metabolism via the 16-alpha-hydroxylation pathway; thus, a prediction of the mechanism by which obesity could increase breast cancer risk would be through a lowering of the 2:16 ratio in favor of the 16 pathway
  • increased BMI was associated with a lower 2:16 OHE ratio
  • Our data show a significant association between alcohol use, defined as at least one drink per day or an average of seven per week, and 2:16 OHE ratio
  • ...10 more annotations...
  • An alcohol-induced rise in estrogens as a consequence of alcohol catabolism in the liver has been reported
  • The only study that looked at the association between alcohol and wine consumption in healthy women did not report a clear association
  • smoking has been reported to increase induction of the 2-hydroxylation metabolic pathway (24). However, the few epidemiological studies conducted on healthy women showed no difference in estrogen metabolites with smoking status (22) or smoking dose (20), in line with our findings.
  • Family history of a first-degree family member with breast cancer confers a 2- to 4-fold risk of developing breast cancer
  • 16% of breast cancers are due to unidentified hereditary factors
  • Estrogen metabolism occurs through enzymes whose activity is determined by the presence of specific genetic polymorphisms, thus can be defined as unique to each individual.
  • the metabolism is also influenced by a number of environmental factors, which change over a lifetime
  • significantly lower 2:16 OHE ratio in women who have known breast cancer risk factors compared with healthy women
  • There was an additional significant association specifically with BMI and alcohol use, which also supports the evidence that these factors affect estrogen metabolism
  • Profiling estrogen metabolites may identify women who are more likely to develop breast cancer within a population of women with known risk factors
  • Nathan Goodyear on 10 May 12
     
    urinary estrogen metabolites shown to provide insight into breast cancer risk.  This study suggested that a low 2:16 OHE ratio increase breast cancer risk.
Nathan Goodyear

Testosterone and weight loss: the evidence - 0 views

www.ncbi.nlm.nih.gov/...PMC4154787

low T low Testosterone Testosterone men male hormone hormones obesity obese fat adipose tissue visceral fat muscle waist circumference BMI

shared by Nathan Goodyear on 04 Mar 15 - No Cached
    • Nathan Goodyear
      Nathan Goodyear on 04 Mar 15
       
      What a ridiculous statement!
  • Testosterone therapy increases LBM, reduces fat mass and produces sustained and significant weight loss, reduction in waist circumference and BMI
Nathan Goodyear

Effects of testosterone supplementatio... [Clin Endocrinol (Oxf). 2010] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...20718771

hypogonadism low T low Testosterone inflammation metabolic syndrome TNF-alpha CRP IL-1beta BMI obesity insulin leptin men male hormone hormones

shared by Nathan Goodyear on 14 Aug 14 - No Cached
  • Nathan Goodyear on 14 Aug 14
     
    Men with hypogonadism, low T, Testosterone therapy reduced IL-1beta, TNF-alph, and CRP.   In addition, BMI and waist circumference was reduced.  Leptin and insulin decreased as well.
Nathan Goodyear

Strong association between serum levels of leptin and testosterone ... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9302400

low Testosterone men male hormone hormones low T leptin BMI Testosterone

shared by Nathan Goodyear on 27 Oct 14 - No Cached
  • Nathan Goodyear on 27 Oct 14
     
    Low Testosterone in men correlates with increasing BMI and increasing leptin in men.
Nathan Goodyear

http://www.eurjmedres.com/content/pdf/s40001-014-0056-6.pdf - 0 views

www.eurjmedres.com/...s40001-014-0056-6.pdf

Testosterone therapy treatment diet exercise low T low Testosterone low T Diabetes BMI weight HgbA1c hypertension blood pressure men male hormone hormones

shared by Nathan Goodyear on 27 Oct 14 - No Cached
  • Nathan Goodyear on 27 Oct 14
     
    Testosterone therapy in obese men with type II Diabetes and low T improved weight,  lipids, HgbA1c, and blood pressure.  There was more improvement with Leptin than with diet/exercise alone. What is very important is that the control group (diet, exercise, DM meds) had improvement in Testosterone levels, HgbA1c, lipids, BMI, and blood pressure; just not as strong as the treatment arm with Testosterone.
Nathan Goodyear

Berberine Improves Insulin Sensitivity by Inhibiting Fat Store and Adjusting Adipokines Profile in Human Preadipocytes and Metabolic Syndrome Patients - 0 views

www.hindawi.com/...363845

berberine BMI obesity metabolic syndrome leptin leptin resistance insulin resistance adiponectin natural alternative

shared by Nathan Goodyear on 25 Mar 15 - No Cached
  • Nathan Goodyear on 25 Mar 15
     
    Berberine reduced BMI, improved insulin sensitivity, improved leptin sensitivity, and improved leptin:adiponectin ratio levels in people with metabolic syndrome after 3 months.
Nathan Goodyear

Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men: The Journal of Clinical Endocrinology & Metabolism: Vol 86, No 2 - 0 views

press.endocrine.org/...jcem.86.2.7219

low t low Testosterone Testosterone SHBG FAI free androgen index male hormone hormones aging obesity

shared by Nathan Goodyear on 30 Mar 15 - No Cached
  • NUMEROUS CROSS-SECTIONAL INVESTIGATIONS have demonstrated lower concentrations of circulating testosterone (T) and/or free T in older men
  • Two small-scale longitudinal investigations have observed decreases, with aging, in total T
  • T levels decline at a more or less constant rate, with age, in men, with no period of accelerated decline
  • ...15 more annotations...
  • aging in men is associated with decreases in bone mineral density (BMD) (18, 19), lean body and muscle mass
  • strength (22, 23) and aerobic capacity (24), as well as with increases in total and abdominal body fat, low-density lipoprotein cholesterol, and/or low-density lipoprotein/high-density lipoprotein cholesterol ratios (25, 26, 27, 28), all of which also occur in nonelderly hypogonadal men
  • Most (1, 5, 6, 7, 8, 9), but not all (10, 11, 12), cross-sectional studies have demonstrated a decrease, with age, in total T in men
    • Nathan Goodyear
      Nathan Goodyear on 30 Mar 15
       
      FAI: 100 x total Testosterone nmol/L/SHBG nmol/L
    • Nathan Goodyear
      Nathan Goodyear on 30 Mar 15
       
      These numbers do point to an increase in ng/dl decline in Total Testosterone with increasing age (decade group)
  • total T, but not free T index, tended to decrease with greater BMI is consistent with prior studies showing that obesity is associated with decreases in both SHBG and total T, with an unchanged T-to-SHBG ratio
  • The conventional definition for T levels is statistical (values more than 2 sd below the mean), rather than functional. Such a definition does not reflect clinical realities, such as the existence of characteristic individual set points for circulating hormone levels, below which one, but not another, individual may develop metabolic changes of hormone deficiency; nor does it address the concept of reserve capacity, the possibility that persons with hormone levels 2 sd below the population mean still may have adequate hormone concentrations to meet their metabolic needs.
    • Nathan Goodyear
      Nathan Goodyear on 30 Mar 15
       
      good explanation of problems with just using a number to define low T
  • both T and free T index (a calculated value related to free or bioavailable T) decreased progressively at a rate that did not vary significantly with age, from the third to the ninth decades.
  • contrasts with other studies showing diminished free, as well as total, T in with increasing total (48) or abdominal (49) obesity in men.
  • Our analysis of date-adjusted T and free T index levels, by decade, showed that relatively high numbers of older men in this generally healthy population had at least one hypogonadal value (defined as below the 2.5th percentile for young men)
  • The issue of how properly to define hypogonadism, or indeed any hormone deficiency, remains problematic
  • The decrease in free T index was somewhat steeper than that of total T, owing to a trend for an increase in SHBG with age
  • LH for gonadal function
  • It would clearly be better to define the lower limit of normal for a hormone as: the blood level at which metabolic and/or clinical sequelae of hormone deficiency begin to appear, or the level below which definite benefits can be demonstrated for hormone supplementation for a significant proportion of the population
  • an effect of aging to lower both total and bioavailable circulating T levels at a relatively constant rate, independent of obesity, illness, medications, cigarette smoking, or alcohol intake
  • Nathan Goodyear on 30 Mar 15
     
    Article highlights the problems with the definition of low T.  This article finds consistent decline in Total Testosterone and FAI with increasing age groups, with a significant portion of men > 60 meeting the required levels for "low T".  This study found a decrease in total T and FAI at a consistent rate independent of variables, such as BMI.    This study did find a decrease in SHBG and total T with obesity; in contrast to other studies.
Nathan Goodyear

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast cancer among postmenopausal women - 1 views

www.ncbi.nlm.nih.gov/...PMC2562592

estrogen metabolism menopause post-menopause post menopause estrogen metabolite 2-OH-estrone 16-alpha-OH-estrone 2:16alpha-OH estrone breast cancer risk hormone hormones

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • 2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
  • previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      whether that risk is increased or decreased
  • it has been hypothesized that metabolism favoring the 2-OH over the 16α-OH pathway may be inversely associated with breast cancer risk (28).
  • ...24 more annotations...
  • they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
  • No significant associations have been observed between 2-OH estrone and breast cancer risk
  • While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
  • In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
  • we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
  • To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
  • circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
  • our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
  • we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
  • Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
  • based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
  • No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      better worded is no consistent, significant associations.   There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
  • we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
  • 16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
  • Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
  • In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
  • Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
  • we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
  • No significant associations have been observed with the 2:16α-OH estrone ratio
  • In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
  • significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
  • it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
  • 4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
  • the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
  • Nathan Goodyear on 21 Aug 14
     
    The risks of estrogen metabolism are not clear cut.  Likely never will be due to the complexity of individual metabolism.  This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer.  Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism.  There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.
  • anonymous on 28 Oct 15
     
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fnfdoc

Causes And Treatment Of Obesity | Your Health Our Priority - 0 views

www.fnfdoc.com/...causes-treatment-obesity

BMI Obesity Causes Treatment

shared by fnfdoc on 01 May 18 - No Cached
  • fnfdoc on 01 May 18
     
    Read how to measure weight and take healthy steps for reducing fats. Obesity is excess of your calories stored in adipose tissues as fats. BMI is used for calculating body mass in relation to stronger muscles.
Nathan Goodyear

Modifiable Risk Factors and Brain Positron Emission Tomography Measures of Amyloid and Tau in Nondemented Adults with Memory Complaints - The American Journal of Geriatric Psychiatry - 0 views

www.ajgponline.org/...fulltext

nutrition exercise mediterranean diet BMI weight alzheimer's disease brain

shared by Nathan Goodyear on 22 Aug 16 - No Cached
  • Nathan Goodyear on 22 Aug 16
     
    Can Alzheimer's be prevented?  New study suggests that nutrition, exercise, and healthy weight are key to Alzheimer's prevention.  A decrease in amyloid plaques and tau tangles were noted in normal BMI individuals, those with greater physical activity and those on a mediterranean diet.
Nathan Goodyear

Testosterone Concentrations In Young P... [Clin Endocrinol (Oxf). 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22970699

obesity overweight men males boys low T low Testosterone low T testosterone estradiol hormone hormones insulin resistance

shared by Nathan Goodyear on 17 Nov 12 - No Cached
  • Nathan Goodyear on 17 Nov 12
     
    New study shows that obese boys/young men pre and post puberty have up to 50% lower testosterone levels than comparative normal BMI counterparts.  Also of note, estradiol levels were not associated with the low testosterone levels.
Nathan Goodyear

PLOS Medicine: Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts - 0 views

www.plosmedicine.org/...journal.pmed.1001383

vitamin D obesity overweight vitamin

shared by Nathan Goodyear on 02 Jul 13 - No Cached
  • Nathan Goodyear on 02 Jul 13
     
    Study finds that obesity is linked to lower vitamin D.  Not that there is merely an association, but that the elevated BMI is the cause of lower vitamin D levels.
Nathan Goodyear

Beneficial effects of Bifidobacterium lactis on lipid profile and cytokines in patients with metabolic syndrome: A randomized trial. Effects of pro... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...27126957

probiotics gut gut health gut flora gut microbiota Bifidobacterium inflammation metabolic syndrome

shared by Nathan Goodyear on 08 Jun 16 - No Cached
  • Nathan Goodyear on 08 Jun 16
     
    only abstract currently available.  Small dose of bifidobacterium lactis in milk found to reduce BMI, total cholesterol, LDL, TNF-alpha, and IL-6 over 45 day study in people with metabolic syndrome.
Nathan Goodyear

Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis - 0 views

www.thelancet.com/...abstract

soda fructose overweight obesity children

shared by Nathan Goodyear on 09 Sep 12 - No Cached
  • Nathan Goodyear on 09 Sep 12
     
    soda intake is associated with increased BMI. Take home, the more soda intake, the higher the obesity. This study looked at children.
Nathan Goodyear

Testosterone and glucose metabolism in men: current concepts and controversies - 0 views

joe.endocrinology-journals.org/...R37.full

Low T Testosterone metabolic syndrome MetS Diabetes men male glucose hormone hormones g

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Around 50% of ageing, obese men presenting to the diabetes clinic have lowered testosterone levels relative to reference ranges based on healthy young men
  • The absence of high-level evidence in this area is illustrated by the Endocrine Society testosterone therapy in men with androgen deficiency clinical practice guidelines (Bhasin et al. 2010), which are appropriate for, but not specific to men with metabolic disorders. All 32 recommendations made in these guidelines are based on either very low or low quality evidence.
  • A key concept relates to making a distinction between replacement and pharmacological testosterone therapy
  • ...59 more annotations...
  • The presence of symptoms was more closely linked to increasing age than to testosterone levels
  • Findings similar to type 2 diabetes were reported for men with the metabolic syndrome, which were associated with reductions in total testosterone of −2.2 nmol/l (95% CI −2.41 to 1.94) and in free testosterone
  • low testosterone is more predictive of the metabolic syndrome in lean men
  • Cross-sectional studies uniformly show that 30–50% of men with type 2 diabetes have lowered circulating testosterone levels, relative to references based on healthy young men
  • In a recent cross-sectional study of 240 middle-aged men (mean age 54 years) with either type 2 diabetes, type 1 diabetes or without diabetes (Ng Tang Fui et al. 2013b), increasing BMI and age were dominant drivers of low total and free testosterone respectively.
  • both diabetes and the metabolic syndrome are associated with a modest reduction in testosterone, in magnitude comparable with the effect of 10 years of ageing
  • In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone with anaemia
  • In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      probably the most important point made in this article
  • low testosterone identifies men with an adverse metabolic phenotype
  • Diabetic men with low testosterone are significantly more likely to be obese or insulin resistant
  • increased inflammation, evidenced by higher CRP levels
  • Bioavailable but not free testosterone was independently predictive of mortality
  • It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker, co-existing because of in-common risk factors.
  • In prospective studies, reviewed in detail elsewhere (Grossmann et al. 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone compared with total testosterone
  • In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident metabolic syndrome
  • low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
  • In cross-sectional studies of men with (Grossmann et al. 2008) and without (Bonnet et al. 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control
  • SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids
  • In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      expensive, laborious process filled with variables
  • Low free testosterone remains inversely associated with insulin resistance, independent of SHBG (Grossmann et al. 2008). This suggests that the low testosterone–dysglycaemia association is not solely a consequence of low SHBG.
  • Experimental evidence reviewed below suggests that visceral adipose tissue is an important intermediate (rather than a confounder) in the inverse association of testosterone with insulin resistance and metabolic disorders.
  • testosterone promotes the commitment of pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
  • testosterone regulates the metabolic functions of mature adipocytes (Xu et al. 1991, Marin et al. 1995) and myocytes (Pitteloud et al. 2005) in ways that reduce insulin resistance.
  • Pre-clinical evidence (reviewed in Rao et al. (2013)) suggests that at the cellular level, testosterone may improve glucose metabolism by modulating the expression of the glucose-transported Glut4 and the insulin receptor, as well as by regulating key enzymes involved in glycolysis.
  • More recently testosterone has been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
  • Interestingly, a reciprocal feedback also appears to exist, given that not only chronic (Cameron et al. 1990, Allan 2013) but also, as shown more recently (Iranmanesh et al. 2012, Caronia et al. 2013), acute hyperglycaemia can lower testosterone levels.
  • There is also evidence that testosterone regulates insulin sensitivity directly and acutely
  • In men with prostate cancer commencing androgen deprivation therapy, both total as well as, although not in all studies (Smith 2004), visceral fat mass increases (Hamilton et al. 2011) within 3 months
  • More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several large observational registry studies
  • Testosterone has also been shown to reduce the concentration of pro-inflammatory cytokines in some, but not all studies, reviewed recently in Kelly & Jones (2013). It is not know whether this effect is independent of testosterone-induced changes in body composition.
  • the observations discussed in this section suggest that it is the decrease in testosterone that causes insulin resistance and diabetes. One important caveat remains: the strongest evidence that low testosterone is the cause rather than consequence of insulin resistance comes from men with prostate cancer (Grossmann & Zajac 2011a) or biochemical castration, and from mice lacking the androgen receptor.
  • Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the age-related decline in testosterone levels
  • there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in testosterone
  • Circulating testosterone, on an average 30%, is lower in obese compared with lean men
  • increased visceral fat is an important component in the association of low testosterone and insulin resistance
  • The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone levels
  • obesity is a dominant risk factor
  • men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat mass is already present before puberty
  • Only 5% of men with type 2 diabetes have elevated LH levels
  • inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
  • Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion from GNRH neurons situated in the preoptic area
  • kisspeptin has emerged as one of the most potent secretagogues of GNRH release
  • hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
  • A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
  • suppression of the diabesity-associated HPT axis is functional, and may hence be reversible
  • Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
  • weight gain and development of diabetes accelerate the age-related decline in testosterone
  • Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone levels than age alone
  • 55% of symptomatic androgen deficiency reverted to a normal testosterone or an asymptomatic state after 8-year follow-up, suggesting that androgen deficiency is not a stable state
  • Weight loss can reactivate the hypothalamic–pituitary–testicular axis
  • Leptin treatment resolves hypogonadism in leptin-deficient men
  • The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
  • Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
  • change in BMI was associated with the change in testosterone (Corona et al. 2013a,b).
  • weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
  • There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
  • in men who improved their glycaemic control over time, testosterone levels increased. By contrast, in those men in whom glycaemic control worsened, testosterone decreased
  • testosterone levels should be measured after successful weight loss to identify men with an insufficient rise in their testosterone levels. Such men may have HPT axis pathology unrelated to their obesity, which will require appropriate evaluation and management.
  • Nathan Goodyear on 04 Feb 14
     
    Article discusses the expanding evidence of low T and Metabolic syndrome.
Nathan Goodyear

Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status - Ng Tang Fui - 2013 - Andrology - Wiley Online Library - 0 views

onlinelibrary.wiley.com/...B667F6B4354AE81F49E3120.f02t04

low T Testosterone obesity weight age diabetes men male hormone hormones

shared by Nathan Goodyear on 19 Feb 14 - No Cached
  • Nathan Goodyear on 19 Feb 14
     
    This study finds that BMI and age are driving forces of low Testosterone.  This study did not find that Diabetes was significantly associated with decreasing Testosterone levels.
Nathan Goodyear

Aging, Androgens, and the Metabolic Syndrome in a Longitudinal Study of Aging: The Journal of Clinical Endocrinology & Metabolism: Vol 92, No 9 - 0 views

press.endocrine.org/...jc.2006-2764

metabolic syndrome MetS metabolic syndrome total Testosterone SHBG men male hormone hormones aging

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    Study finds Total Testosterone and SHBG inversely associated with Metabolic Syndrome.  Free Testosterone and BMI were positively associated with MetS.
Nathan Goodyear

Testosterone deficiency syndrome and cardiovascular health: An assessment of beliefs, knowledge and practice patterns of general practitioners and cardiologists in Victoria, BC - 0 views

www.ncbi.nlm.nih.gov/...PMC3929476

low T Testosterone cardiovascular disease physicians men male hormone hormones

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • 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
  • ...14 more annotations...
  • 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
  • Nathan Goodyear on 03 Mar 14
     
    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

Testosterone 2% Gel Can Normalize Testosterone Con... [J Sex Med. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24283410

testosterone gel therapy treatment men map hormone hormones low T

shared by Nathan Goodyear on 29 Nov 13 - No Cached
  • Nathan Goodyear on 29 Nov 13
     
    Study finds that transdermal testosterone effective in normal and overweight men.  The dosing involved is supra physiologic, especially those with an elevated BMI.  This was likely due to the high dosing to overcome the underlying problem i.e. high aromatase activity.  These studies all need to assess estrogens and inflammatory cytokines to better follow these results
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