low SHBG in post-menopausal women correlates with increased risk of metabolic syndrome. More than that, there is an inverse correlation with SHBG in women and metabolic syndrome components. Also, Increasing components of MetS was correlated with Testosterone and free androgen index.
Large, randomized, double blind, placebo controlled study of 14,641 men found that daily MVA reduced cancer risk by 8%. These were just general multivitamins. Customized would have probably provided better results as they would have met the deficiencies of the individual.
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
Testosterone therapy is complex in hypogonadism. Much of the marketing-based medicine of Low T today is in fact doping. Increasing weight is clearly associated with a declining T level in men. Testosterone therapy should be approach individually and therapies that use the one size fits all approach never work. This is the case whether the use of synthetics or natural hormones are employed. Testosterone has been shown to improve dysglycemia, MetS, reduce fat and increase muscle mass.
20alpha dihydroprogesterone, a 4 pregnene, has been shown to inhibit breast cancer cell proliferation, decrease mets through increased cell adhesion, and increased apoptosis. Here, it has been shown to inhibit aromatase activity. No longer are hormone metabolites to be viewed as waste. They are biological as active if not more so in many cases.
Post menopause women with PCOS have high CVD. PCOS is essentially metabolic syndrome separated by age. Both PCOS and MetS in women is associated with an increase in Testosterone levels.
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.
This population study finds increased risk, significantly more for women vs men, of type II Diabetes with gout. This should come as no surprise as the underlying pathophysiology is the same. Fructose increases Uric acid. Uric acid is a biomarker of MetS. Fructose increases abdominal adiposity and eventually inflammation which leads to diabetes.
Study finds that leptin, PAI-1, and hsCRP are positively associated with increasing metabolic syndrome components. Adiponectin was negative associated with increasing MetS. Not a lot of new info here.
Metabolic Syndrome is associated with CAD. No surprise here, but increase in # of metabolic syndrome parameters was associated with increasing % of Triple vessel disease. No surprise that MetS was associated with TNF-alpha, IL-6, IR, and hsCRP.
The results suggest that elderly men with MetS were more susceptible to autonomic dysfunction in association with chronic lead exposure as measured in patella. The modification by MetS is consistent with a role for oxidative stress in lead toxicity on the cardiovascular system.
Altered cognitive function found in adolescents with non-IR obesity. This worsened with MetS and type II Diabetes. The statement that there is healthy obesity is in error.
Study finds no improvement with glucose control in diabetics. This study looked at moderately controlled diabetes. Studies have previously shown that poorly controlled diabetes definitely benefits more than those with more mild glucose control problems. Additionally, the Testosterone levels in this study would not have met the definition of low T by other studies. So, the question is did these men need T? Second, did the authors design the study long enough to see changes in the insulin sensitivity and glucose control? Abstract only available and thus I don't have access to that information. Third, and this might support the 2nd point, increased lean mass and decreased fat mass was found. This points to positive metabolic change. Would this have, given more time, resulted in improved glucose control?
No change in visceral adiposity was seen. This finding, also, is not new. Testosterone therapy does not improve visceral adiposity. Though, increasing fat adiposity, low Testosterone, and associated increase in systemic inflammatory cytokine production results in visceral adiposity, Testosterone therapy does reverse the visceral adiposity.