E2 and the inflammatory adipocytokines tumour necrosis factor α (TNFα) and interleukin 6 (IL6) inhibit hypothalamic production
of GNRH and subsequent release of LH and FSH from the pituitary
Leptin, an adipose-derived hormone with a well-known role
in regulation of body weight and food intake, also induces LH release under normal conditions via stimulation of hypothalamic
GNRH neurons
In human obesity, whereby adipocytes are producing elevated amounts of leptin, the hypothalamic–pituitary axis becomes
leptin resistant
there is evidence from animal studies
that leptin resistance, inflammation and oestrogens inhibit neuronal release of kisspeptin
Beyond hypothalamic action, leptin also directly inhibits the stimulatory action of gonadotrophins on the Leydig cells
of the testis to decrease testosterone production; therefore, elevated leptin levels in obesity may further diminish androgen
status
increasing insulin resistance assessed by glucose tolerence test and hypoglycemic clamp was shown to be associated
with a decrease in Leydig cell testosterone secretion in men
ADT for the treatment of prostatic carcinoma in some large epidemiological studies has been shown to be associated with an
increased risk of developing MetS and T2DM
Non-diabetic men undergoing androgen ablation show increased occurrence of new-onset diabetes and demonstrate elevated
insulin levels and worsening glycaemic control
Prostate cancer patients with pre-existing T2DM show a further deterioration of insulin resistance and worsening of diabetic
control following ADT
The response to testosterone replacement of insulin sensitivity is in part dependent on the androgen receptor (AR)
Low levels of testosterone have been associated with an atherogenic lipoprotein profile, characterised by high LDL and triglyceride
levels
a positive correlation between serum testosterone and HDL has been reported in both healthy and diabetic
men
up to 70% of the body's insulin sensitivity is accounted for by muscle
Testosterone deficiency is associated with a decrease in lean body mass
relative muscle mass is inversely associated
with insulin resistance and pre-diabetes
GLUT4 and IRS1 were up-regulated in cultured adipocytes and skeletal
muscle cells following testosterone treatment at low dose and short-time incubations
local conversion of testosterone to
DHT and activation of AR may be important for glucose uptake
inverse correlation between testosterone levels and adverse mitochondrial function
orchidectomy of male Wistar rats and associated testosterone deficiency induced increased absorption of glucose
from the intestine
(Kelley & Mandarino 2000). Frederiksen et al. (2012a) recently demonstrated that testosterone may influence components of metabolic flexibility as 6 months of transdermal testosterone
treatment in aging men with low–normal bioavailable testosterone levels increased lipid oxidation and decreased glucose oxidation
during the fasting state.
Decreased lipid oxidation coupled with diet-induced chronic FA elevation is linked to increased accumulation of myocellular
lipid, in particular diacylglycerol and/or ceramide in myocytes
In
the Chang human adult liver cell line, insulin receptor mRNA expression was significantly increased following exposure to
testosterone
Testosterone deprivation via castration of male rats led to decreased expression of Glut4 in liver tissue, as well as adipose and muscle
oestrogen was found to increase the expression of insulin receptors in insulin-resistant HepG2 human liver cell
line
FFA decrease hepatic
insulin binding and extraction, increase hepatic gluconeogenesis and increase hepatic insulin resistance.
Only one, albeit large-scale,
population-based cross-sectional study reports an association between low serum testosterone concentrations and hepatic steatosis
in men (Völzke et al. 2010)
This suggests that testosterone may confer some of its beneficial effects on hepatic lipid metabolism via conversion to
E2 and subsequent activation of ERα.
hypogonadal men exhibiting a reduced lean body mass and an increased fat mass, abdominal or central obesity
visceral adipose tissue was inversely correlated with
bioavailable testosterone
there was no change in visceral fat mass in aged men with low testosterone levels
following 6 months of transdermal TRT, yet subcutaneous fat mass was significantly reduced in both the thigh and the abdominal
areas when analysed by MRI (Frederiksen et al. 2012b)
ADT of prostate cancer patients increased both visceral and subcutaneous abdominal fat in a 12-month prospective
observational study (Hamilton et al. 2011)
Catecholamines are the major lipolysis regulating hormones in man and
regulate adipocyte lipolysis through activation of adenylate cyclase to produce cAMP
deficiency of androgen action decreases lipolysis and is primarily
responsible for the induction of obesity (Yanase et al. 2008)
may be some regional differences in the action of testosterone on
subcutaneous and visceral adipose function
proinflammatory adipocytokines IL1, IL6 and TNFα are increased in obesity with a downstream effect that stimulates
liver production of CRP
observational evidence suggests that
IL1β, IL6, TNFα and CRP are inversely associated with serum testosterone levels in patients
TRT has been reported to significantly reduce these proinflammatory mediators
This suggests a role for AR in the metabolic actions of testosterone on fat accumulation and adipose tissue inflammatory
response
testosterone treatment may have beneficial effects on preventing the pathogenesis of obesity by inhibiting adipogenesis,
decreasing triglyceride uptake and storage, increasing lipolysis, influencing lipoprotein content and function and may directly
reduce fat mass and increase muscle mass
Early interventional
studies suggest that TRT in hypogonadal men with T2DM and/or MetS has beneficial effects on lipids, adiposity and parameters
of insulin sensitivity and glucose control
Evidence that whole-body insulin sensitivity is reduced in testosterone deficiency and increases with testosterone replacement
supports a key role of this hormone in glucose and lipid metabolism
Impaired insulin sensitivity in these three tissues is
characterised by defects in insulin-stimulated glucose transport activity, in particular into skeletal muscle, impaired insulin-mediated
inhibition of hepatic glucose production and stimulation of glycogen synthesis in liver, and a reduced ability of insulin
to inhibit lipolysis in adipose tissue
Increased aromatase activity in men increases testosterone to estrogen production, which causes increase in SHBG and thus a reduction in the bioavailability of free testosterone.
Testosterone levels, measured as total, bioavailable and free, found to be associated with age and central (not visceral) obesity in those men with type I and II Diabetes. Weakly with symptoms of low T and ED.
I think the authors missed the points to be taken from their research:prostate cancer patients had "lower concentrations of total Testosterone, free Testosterone, and bioavailable Testosterone" versus controls that were prostate cancer free. This provides additional support that prostate cancer is not a androgen driven disease.
Men with type II diabetes have lower Testosterone levels when compared to none diabetics. This study found an increased mortality with low T in those with type II Diabetes. The main association was found with bioavailable Testosterone. Total Testosterone is proving useless as a functional tool. Additionally, Testosterone therapy reduced mortality in those with Diabetes.
low T (total, free, and bioavailable) associated with advanced cancer, decreased survival, increased systemic inflammation (CRP), and weight loss in male patients.
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
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
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.
Meta-analysis finds that for every oral daily intake of 100 mg vitamin C, the risk of total mortality was decreased by 27% and the breast cancer specific mortality was decreased by 22%. A lot of potential variables that can play into this equation. However, oral vitamin C is poorly bioavailable, yet according to this meta-analysis, does provide significant health benefits and even prevention. If health and breast cancer prevention is a goal, then vitamin C needs to play a role in your daily intake.
Study finds that low Total T and "bioavailable", also known as free, Testosterone is associated with an increase in carotid intima-media thickness, which is a marker of CVD. Higher CRP increased the IMT in those with low T.
Older men, 70-89, Testosterone in the middle range of normal and higher DHT was associated with the lowest death rates. Estradiol was not found to be associated. This study only looked at Total levels, free bioavailable levels were not assessed. This study also highlights the basic thought, that more is not always better as it pertains to Testosterone. It also highlights the importance of DHT. Testosterone is a pro hormone.
Interesting finding in this study. They looked at Total Testosterone and bioavailable Testosterone and found that antidepressant therapy increased both values post treatment. This is counter to what has been readably seen in men--with a decline. The abstract here does not point disclose the actual Testosterone numbers. I wonder if the well known disruption of the CYP enzymes by antidepressants slowed clearance and increased Testosterone levels. This study did not look at other hormones or inflammatory cytokines. Very tunneled vision study. Nothing can be drawn from this study.
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.
review of activity of garlic against H.pylori. Most of the studies are in vitro. Most of the activity against H.pylori is via allicin, though studies have have shown poor bioavailability with allicin.
increased abdominal and visceral adipose tissue (VAT) – found in women and marked by low sex hormone binding globulin (SHBG) and high bioavailable testosterone (BT) – is related to the metabolic risk profile
In men, increased BT is related to decreased abdominal obesity and a decrease in the metabolic risk profile
Only abstract available here. Race (black vs white) is associated with changes in obesity effects on adrogenicity, particularly in women. One wonders if this is a result of other variables i.e.vitamin D.