Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates
of all‐cause and cardiovascular‐related mortality.39,41,46–47 Patients suffering from CAD,13–18 CHF,137 T2DM,25–26 and obesity27–28
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shared by Nathan Goodyear on 21 Aug 13
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Analysis of Relations between serum levels of Epitestosterone, Estradiol, Testosterone,... - 0 views
www.biomed.cas.cz/...49_S113.pdf
PSA hormone hormones BPH Prostate cancer prostate cancer Epitestosterone men male aromatase Estradiol IGF-1
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Great confusion exists in the medical profession about Testosterone and PSA and the health of the prostate. The conversion of Estrogen, whether E2 or E1, and other variables are responsible for increases in PSA while on Testosterone therapy. This study points out that Estradiol in men stimulates cell line growth of prostate cancer. In contrast, Epitestosterone, an androgen metabolite, has antiandrogen, inhibits this estrogen activity. Epitestosterone exists in an inverse relationship to Estradiol and IGF-1.
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Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Lite... - 0 views
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have all been shown to have lower levels of endogenous testosterone compared with those in healthy controls. In addition, the severity of CAD15,17,29–30 and CHF137 correlates with the degree of testosterone deficiency
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In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having no effect on LVEF
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testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration of type I muscle fibers
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Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin A1c in diabetics26,68–69 and to lower the BMI in obese patients.
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Lower levels of endogenous testosterone have been associated with longer duration of the QTc interval
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negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries, abdominal aorta, and thoracic aorta
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These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
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Current guidelines from the Endocrine Society make no recommendations on whether patients with heart disease should be screened for hypogonadism and do not recommend supplementing patients with heart disease to improve survival.
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The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age group
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since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
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Testosterone levels are lower in patients with chronic illnesses such as end‐stage renal disease, human immunodeficiency virus, chronic obstructive pulmonary disease, type 2 diabetes mellitus (T2DM), obesity, and several genetic conditions such as Klinefelter syndrome
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A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during their lifetimes
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There are 2 major potential confounding factors that the older studies generally failed to account for. These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD.
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The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
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The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
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The biologically active subfraction of testosterone, also referred to as bioavailable testosterone, is either loosely bound to albumin or circulates freely in the blood, the latter referred to as free testosterone
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It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free testosterone
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it can be argued that using the biologically active form of testosterone to evaluate the association with CAD will produce the most reliable results
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English et al14 found statistically significant lower levels of bioavailable testosterone, free testosterone, and free androgen index in patients with catheterization‐proven CAD compared with controls with normal coronary arteries
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patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable testosterone
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In conclusion, existing evidence suggests that men with CAD have lower levels of endogenous testosterone,13–18 and more specifically lower levels of bioavailable testosterone
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In a meta‐analysis of these 7 population‐based studies, Araujo et al41 showed a trend toward increased cardiovascular mortality associated with lower levels of total testosterone, but statistical significance was not achieved (RR, 1.25
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the authors showed that a decrease of 2.1 standard deviations in levels of total testosterone was associated with a 25% increase in the risk of cardiovascular mortality
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the relative risk of all‐cause mortality in men with lower levels of total testosterone was calculated to be 1.35
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higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
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Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause mortality and cardiovascular mortality
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studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates of all‐cause and cardiovascular mortality
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It may be possible that using bioavailable testosterone to perform mortality analysis will yield more accurate results because it prevents the biologically inactive subfraction of testosterone from playing a potential confounding role in the analysis
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In more recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial ischemia in men with CAD
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The improvement in myocardial ischemia was shown to occur in response to both acute and chronic testosterone therapy and seemed to be independent of whether an intravenous or transdermal formulation of testosterone was used.
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There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells
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Experimental studies suggest that the most likely mechanism of action for testosterone on vascular smooth muscle cells is via modulation of action of non‐ATP‐sensitive potassium ion channels, calcium‐activated potassium ion channels, voltage‐sensitive potassium ion channels, and finally L‐type calcium ion channels
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Corona et al confirmed those results by demonstrating that not only total testosterone levels are lower among diabetics, but also the levels of free testosterone and SHBG are lower in diabetic patients
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Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome.
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Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM
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authors demonstrated a statistically significant increase in the incidence of T2DM in subjects receiving gonadotropin‐releasing hormone antagonist therapy. In addition, a significant increase in the rate of myocardial infarction, stroke, sudden cardiac death, and development of cardiovascular disease was noted in patients receiving antiandrogen therapy.67
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Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose
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Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared with those in nondiabetics
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insulin seems to be acting as a stimulant for the hypothalamus to secret gonadotropin‐releasing hormone, which consequently results in increased testosterone production. It can be argued that decreased stimulation of the hypothalamus in diabetics secondary to insulin deficiency could result in hypogonadotropic hypogonadism
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This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. On the other hand, given that adipose tissue has a higher concentration of the enzyme aromatase, it could be that increased adipose tissue results in more testosterone being converted to estrogen, thereby causing hypogonadism. Third, increased abdominal obesity may cause reduced testosterone secretion by negatively affecting the hypothalamus‐pituitary‐testicular axis. Finally, testosterone may be the key factor in activating the enzyme 11‐hydroxysteroid dehydrogenase in adipose tissue, which transforms glucocorticoids into their inactive form.
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increasing age may alter the association between testosterone and CRP. Another possible explanation for the association between testosterone level and CRP is central obesity and waist circumference
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Bai et al have provided convincing evidence that testosterone might be able to shorten the QTc interval by augmenting the activity of slowly activating delayed rectifier potassium channels while simultaneously slowing the activity of L‐type calcium channels
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Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
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Studies have shown that levels of endogenous testosterone are inversely associated with IMT of the carotid artery,126–128,32,129–130 as well as both the thoracic134 and the abdominal aorta
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1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression of carotid artery IMT
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another study has reported that decreased levels of total and bioavailable testosterone are associated with progression of atherosclerosis in the abdominal aorta
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These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
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Czesla et al successfully demonstrated that the muscle specimens that were exposed to metenolone had a significant shift in their composition toward type I muscle fibers
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Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are associated with enhanced strength and physical capability
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It has been shown that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
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Studies have shown that men with CHF suffer from reduced levels of total and free testosterone.137 It has also been shown that reduced testosterone levels in men with CHF portends a poor prognosis and is associated with increased CHF mortality.138 Reduced testosterone has also been shown to correlate negatively with exercise capacity in CHF patients.
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Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
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the results of the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not cause an increase in the rate of adverse cardiovascular events
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Data from 3 meta‐analyses seem to contradict the commonly held belief that testosterone administration may increase the risk of developing prostate cancer
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One meta‐analysis reported an increase in all prostate‐related adverse events with testosterone administration.146 However, when each prostate‐related event, including prostate cancer and a rise in PSA, was analyzed separately, no differences were observed between the testosterone group and the placebo group
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the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase the risk of adverse cardiovascular events
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the authors correctly point out the weaknesses of their study which include retrospective study design and lack of randomization, small sample size at extremes of follow‐up, lack of outcome validation by chart review and poor generalizability of the results given that only male veterans with CAD were included in this study
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the studies that failed to find an association between testosterone and CRP used an older population group
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low testosterone may influence the severity of CAD by adversely affecting the mediators of the inflammatory response such as high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor–α
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Good review of Testosterone and CHD. Low T is associated with increased all cause mortality and cardiovascular mortality, CAD, CHF, type II diabetes, obesity, increased IMT, increased severity of CAD and CHF. Testosterone replacement in men with low T has been shown to improve exercise tolerance in CHF, improve insulin resistance, improve HgbA1c and lower BMI in the obese.
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Net Neutrality: Battle to 'save the Internet' - 0 views
onlywheelchair.blogspot.in/...y-battle-to-save-internet.html
Net Neutrality: Battle to 'save the Internet' Internet service providers Net Neutrality KP 80 power standing wheelchair control the traffic
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Net neutrality is one of the biggest issue debated globally by the telecom regulators and it is also in the process of finalising what will be a landmark recommendation for Indian telecom. The important aspects of Net neutrality are: Internet service providers should enable access to all content and applications regardless of the source. The Internet service provider from whom buy internet pack, should not under any circumstance be able to control how exactly use it and it's upto how you use the data. All websites can co-exist without hampering others and all websites are accessible at the same speed and no particular website of application is favoured. All web sites and content creators are treated equal, and it don't have to pay extra for faster Internet speed to a particular site/service. The concept of net neutrality doesn't exist legally but most companies have Net Neutrality is simply the Internet Freedom - Free, Fast and Open Internet for all. Net Neutrality is the principle that Internet service providers (ISPs) should give consumers access to all and every contents and application on an equal basis, treating all Internet traffic equally. Today, if there's something that makes everyone across the world "Equal" is nothing but the Internet. Equality over the Internet means, the richest man in the world has the same rights to access the Internet as the poorer. And this is what "Net Neutrality" aims at adhered to it until now. With the Internet taking the world into its folds, Internet Service Providers across the world are trying to encash this potent commodity and trying to control the traffic. Karma Healthcare KP-80 Standing Wheelchair is a compact and fully powered wheelchair designed for budget. The front-wheel drive provides agile control for the chair to negotiate various indoors and out. It comes with the innovative seat and wide range of power backrest angle adjustment (80~120 degree).
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shared by Nathan Goodyear on 05 Jan 16
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Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabitin... - 0 views
www.sciencedirect.com/...S0147651315301093
low T low Testosterone hormones environment EDC endocrine disruptor endocrine disruptors fish estrogen
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Is our effect on the environment and the environments, in turn, effect on us politics or science? It is science that is manipulated by politicians for political gain/power. In this study of male small/large mouth bass in NE America are found to have significant female characteristics i.e. eggs where testes should exist...where none should exist. The numbers were as high as 85% in the small mouth base compared to 27% for the large mouth bass. Is there any wonder we have a low T epidemic in men? The most likely cause are endocrine disruptors. It is a concern that the authors did not look for endocrine disruptors in the water at the time of this study of the fish.
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shared by star yu on 17 Apr 16
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En Shijiazhuang Hospital Enfermedades de Riñón, Existe una Terapia Avanzada - 0 views
www.hospitalrenal.com/...1392.html
En Shijiazhuang Hospital Enfermedades de Riñón Existe una Terapia Avanzada
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Hoy en día, hay muchas personas tiene la enfermedad renal crónica, ellos no saben qué pueden tomar. Generalmente la mayoría de los pacientes hacen la diálisis para mantener la vida normal. Sin embargo, la diálisis no es una opción adecuada. Ahora existe la terapia de las células alternatica a la diáslisis.
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shared by Nathan Goodyear on 28 Jan 14
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Progesterone metabolites regulate induction, growth, and suppression of estrogen- and p... - 0 views
www.ncbi.nlm.nih.gov/...PMC3706910
progesterone metabolites metabolite 5-alpha pregnene 5-alpha pregnenes 5alpha-dihydroprogesterone 4-pregnene 4-pregnenes 3alpha-dihydroprogesterone breast cancer ER PR hormone hormones receptors estrogen
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in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines
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Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP
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When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa
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Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors
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Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions
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The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress
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hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions.
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Our previous in vitro studies had shown that breast tissues and cell lines readily convert progesterone to 5α-pregnanes, such as 5αP, and delta-4-pregnenes, such as 3αHP (Figure (Figure1),1), and that tumorous breast tissues [15] and tumorigenic breast cell lines [16] produce higher levels of 5αP and lower levels of 3αHP than do normal breast tissues and nontumorigenic cell lines
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The progesterone metabolism studies suggested that increases in 5αP and decreases in 3αHP production accompany the shift toward breast cell neoplasia and tumorigenicity
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In vitro studies on five different human breast cell lines showed that cell proliferation and detachment are significantly increased by 5αP and decreased by 3αHP
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the prevailing theory of hormonal regulation of breast cancer, as well as hormone-based therapies, revolves around estrogen and/or progesterone and ER/PR-positive breast cells and tumors.
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Not only do these "receptor-negative" breast cancers fail to benefit from current hormonal therapies, but they also generally exhibit more-aggressive biologic behaviors and poorer prognosis than the receptor-positive ones
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The results of the studies reported here show for the first time that the progesterone metabolites, 5αP and 3αHP, act as hormones that regulate ER/PR-negative breast tumor formation, growth, and regression
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The onset of the ER/PR-negative human breast cell tumors in mice was considerably accelerated, and the growth significantly stimulated, by just one or two applications of 5αP
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In contrast, 3αHP retarded onset of tumor formation, suppressed tumor growth, and inhibited or regressed existing 5αP-induced tumors
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When both hormones were administered simultaneously, the effects of one were abrogated by the effects of the other.
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The 5αPR and 3αHPR (which are associated with the plasma membranes of both ER/PR-positive [19] and ER/PR-negative [29] cells) are distinct from each other and from known ER, PR, androgen, and corticosteroid receptors, and lack affinity for other steroids, such as progesterone, estrogen, androgens, corticosteroids, and other progesterone metabolites
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Levels of 5αPR are upregulated by 5αP itself and estradiol, and downregulated by 3αHP in both ER/PR-positive and -negative cells
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ndications are that 5αP acts via the surface receptor-linked mitogen-activated protein kinase (MAPK; Erk1/2) pathway; 5αP significantly stimulates activation of Erk1/2 [30], increases the Bcl-2/Bax expression ratio [18] and actin depolymerization [31], and decreases expression of actin and adhesion plaque-associated vinculin [31], resulting in decreased apoptosis and increased mitosis and cell detachment
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3αHP appears to suppress protein kinase C (PKC), phospholipase C (PLC), Ca2+ mobilization (unpublished observations), and the Bcl-2/Bax expression ratio [18], and increases expression of the cell-cycle inhibitor p21 [18], resulting in increased apoptosis and decreased proliferation and detachment of breast cell lines.
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the tumors, which on average had about threefold higher concentrations of 5αP than the respective sera, and >10-fold higher 5αP than 3αHP levels
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Previous in vitro metabolism studies showed that human breast tumor tissues convert significantly more progesterone to 5α-pregnanes like 5αP and less to 4-pregnenes like 3αHP than do paired normal (nontumorous) tissues
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Similar differences in progesterone metabolism and enzyme gene expressions were observed between tumorigenic and nontumorigenic breast cell lines
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The current findings, along with the previous in vitro studies, suggest that the relative concentrations of 5αP and 3αHP in the breast microenvironment constitute important autocrine/paracrine determinants not only for tumorigenesis but also for potential regression of tumors and the maintenance of normalcy of ER/PR-negative breast cells/tissues.
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Evidence presented here shows that a high concentration of 5αP, relative to 3αHP in the microenvironment, promotes initiation and growth of tumors, whereas a higher concentration of 3αHP, relative to 5αP, suppresses tumorigenesis and promotes normalcy
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in the 3αHP-treated mice, the elevated 3αHP levels, relative to 5αP, in the microenvironment could have opposed progression to xenograft neoplasia by its inherent anticancer actions and the suppression of 5αP synthesis and 5αPR expression
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the opposing actions of the progesterone metabolites also appear to exert some control over the estrogen-regulated effects on breast cancer by their ability to modulate ER numbers in ER-positive cells
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because both ER/PR-negative and ER/PR-positive, as well as normal and tumorigenic human breast cell lines, have been shown to respond to 5αP and 3αHP in vitro, it is suggested that these endogenously produced progesterone metabolites may also play regulatory hormonal roles in ER/PR-positive breast cancers, as well as in the maintenance of normalcy in nontumorous breast tissues.
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The in vivo data provide further evidence that progesterone metabolites, such as 5αP and 3αHP, deserve to be considered as active hormones in their own right, rather than inactive waste products
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Cross-kingdom inhibition of breast cancer growth by plant miR159 - 0 views
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MicroRNAs (miRNAs), a major family of small RNAs, are ∼23 nt-long single strands of RNA that bind to mRNA transcripts to inhibit their translation
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The group demonstrates that the plant miRNA miR168 may be taken up through dietary intake to inhibit the expression of its target low-density lipoprotein receptor 1 in the liver21, providing the first evidence that miRNA in food may influence gene expression in mammalian organs.
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A more recent finding by the same group shows that a plant miRNA from honeysuckle is able to inhibit Influenza A replication22, indicating that plant miRNAs may be useful for treating human diseases.
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We found that plant miR159 could be detected in human sera and its levels were inversely correlated with BC incidence and progression.
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We further identified TCF7 as a mammalian target for miR159 and showed the anti-proliferative function of miR159 in BC cells using in vitro and in vivo models, demonstrating for the first time that a plant miRNA is able to influence BC cell growth.
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certain dietary miRNAs from plants and other species may serve as highly affordable and powerful means of treatment with minimal inconvenience to patients.
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miR159 which (using a synthetic mimic) targets TCF7 to inhibit the proliferation of cells whose growth is dependent on TCF7 such as the BC cells MDA-MB-231
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our study using a BC model clearly indicates the anti-tumor effect of orally administered synthetic miR159 in its naturally existing form with the plant-specific 2'-O-methylation, suggesting the feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track
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shared by Nathan Goodyear on 17 Jun 13
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Glyphosate induces human breast cancer cel... [Food Chem Toxicol. 2013] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...23756170
glyphosate xenoestrogen breast cancer cancer ER alpha ER beta food human
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http://onlinelibrary.wiley.com/store/10.1002/art.11105/asset/11105_ftp.pdf;jsessionid=4... - 0 views
onlinelibrary.wiley.com/...4193903EA1042174A607429.f03t01
Lupus Testosterone DHEA Progesterone autoimmune disease
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Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age... - 0 views
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shared by Nathan Goodyear on 20 Feb 12
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Large Differences in Testosterone Excretion in Korean and Swedish Men Are Strongly Asso... - 0 views
jcem.endojournals.org/...687.full
Testosterone epi-Testosterone metabolism UGT2B17 SNP korean swedish
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men with UGT2B17 found to be poor metabolizers of endogenous Testosterone. Normally, epi-Testosterone and Testosterone exist in a relative 1:1 ratio, However, in these individuals with this SNP, they will have slightly elevated Testosterone levels due to disrupted phase II testosterone metabolism (glucuronidation). This is found in 60% of Asian men, 50% of black men, and 1% in white men.
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Urinary Cortisol and Cortisol Metabolite Excretion in Chronic Fatigue Syndrome - 0 views
www.psychosomaticmedicine.org/...578.full.pdf
CFS chronic fatigue syndrome salivary saliva cortisol metabolism metabolization
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shared by Nathan Goodyear on 17 Jul 12
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Acute Anti-Ischemic Effect of Testosterone in Men With Coronary Artery Disease - 0 views
circ.ahajournals.org/...1666.full
low T low Testosterone CAD CVD testosterone artery dilation heart myocardium myocardial ischemia cardiology men male hormone hormones
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Diabetes mellitus and the risk of dementia: The Ro... [Neurology. 1999] - PubMed - NCBI - 0 views
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JAMA Network | Archives of Internal Medicine | Statin Use and Risk of Diabetes Mellitus... - 0 views
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The metabolic syndrome and inflamm... [Nutr Metab Cardiovasc Dis. 2004] - PubMed - NCBI - 0 views
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Aluminum vaccine adjuvants appear to contribute to the rising - 0 views
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shared by Nathan Goodyear on 04 Feb 14
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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
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Around 50% of ageing, obese men presenting to the diabetes clinic have lowered testosterone levels relative to reference ranges based on healthy young men
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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.
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A key concept relates to making a distinction between replacement and pharmacological testosterone therapy
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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
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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
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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.
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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
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In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone with anaemia
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In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
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It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker, co-existing because of in-common risk factors.
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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
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In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident metabolic syndrome
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low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
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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
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SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids
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In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
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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.
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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.
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testosterone promotes the commitment of pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
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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.
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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.
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More recently testosterone has been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
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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.
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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
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More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several large observational registry studies
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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.
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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.
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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
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there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in testosterone
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increased visceral fat is an important component in the association of low testosterone and insulin resistance
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The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone levels
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men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat mass is already present before puberty
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inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
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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
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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
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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
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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
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Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone levels than age alone
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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
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The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
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Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
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weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
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There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
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in men who improved their glycaemic control over time, testosterone levels increased. By contrast, in those men in whom glycaemic control worsened, testosterone decreased
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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.
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Acute and short term chronic testost... [J Clin Endocrinol Metab. 2014] - PubMed - NCBI - 0 views
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Study finds that Testosterone regulates glucose metabolism, in part, through adiponectin production. Early state of low T will slow the use of fats as a source of fuel and this results in an increased energy balance and results in the increased adiponectin production to increase metabolism. Testosterone and adiponectin exist in an inverse relationship. This study does not mimic normal physiology. Men with low T are unhealthy with significant metabolic dysfunction. These young, "healthy" men were induced to a low T state--that is not a clear picture as the physiology of a "young healthy" man is quite different than that of one with low T. Testosterone conversion to DHT increases GLUT4 and thus glucose uptake--another mechanism of Testosterone's effect on glucose metabolism.