it is established that androgen modulates various neurotransmitters in the CNS. Testosterone decreases γ-aminobutyric acid concentration in the hypothalamus, which is blocked by flutamide, a testosterone receptor blocker (14, 15). Testosterone, probably by its conversion to estradiol, increases serotonin transporter mRNA expression in dorsal raphe nucleus (16), and it also increases the density of 5-hydroxytryptamine receptors and serotonin transporter sites in the forebrain (3, 16) of castrated male rats.
Group items matching
in title, tags, annotations or url
2More
Testosterone Treatment Enhances Regional Brain Perfusion in Hypogonadal Men: The Journa... - 0 views
press.endocrine.org/...jc.2002-020632
low T low testosterone brain cognition ED Testosterone therapy male hormones
shared by Nathan Goodyear on 09 Jan 17
- No Cached
1More
Neuroestradiol in the Hypothalamus Contributes to the Regulation of Gonadotropin Releas... - 0 views
14More
The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views
-
Sex steroid hormones are primarily responsible for sex difference in adult HPA function; androgens inhibit whereas estrogens enhance HPA axis activation after a stressor
-
the PVN contains relatively high levels of AR (Bingaman et al., 1994; Zhou et al., 1994) and ERβ (Alves et al., 1998; Hrabovszky et al., 1998; Somponpun and Sladek, 2003) but is essentially devoid of ERα
-
the nonaromatizable androgen DHT and the nonselective ER ligand E2 influence HPA reactivity by acting on neurons within or surrounding the PVN
- ...9 more annotations...
-
inhibitory action of DHT is detectable at both the level of hormone secretion as well as PVN c-fos mRNA expression
-
the inhibition can be mimicked by the DHT metabolite 3β-diol and by the subtype selective ERβ agonist DPN
-
the ability of the ER antagonist tamoxifen, but not the AR antagonist flutamide, to block the inhibitory actions of DHT, speaks to the intracellular mechanism by which this inhibitory signal might be transduced.
-
the DHT metabolite 3β-diol and the ERβ-subtype-selective agonist DPN suppressed ACTH, corticosterone, and c-fos mRNA responses to restraint stress in a manner similar to DHT
-
metabolism of DHT to 3β-diol and subsequent binding to ERβ can be inhibitory to HPA reactivity, and this is one possible mechanism for the action of DHT.
-
Our data also suggest that E2 enhances the reactivity of the HPA axis to stress by acting on or near neurons of the PVN
-
these studies suggest that ERβ, within the male hypothalamus, acts to inhibit the HPA axis and that the inhibitory effects of DHT may be, at least in part, via its intracellular conversion to 3β-diol and subsequent binding to ERβ
1More
Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regula... - 0 views
24More
Review of health risks of low testosterone and testosterone administration - 0 views
www.ncbi.nlm.nih.gov/...PMC4391003
low Testosterone low T Testosterone men male hormone hormones health
shared by Nathan Goodyear on 28 Apr 15
- No Cached
-
Hypogonadism may be defined either as serum concentration of T (either total T, bioavailable T or free T) or as low T plus symptoms of hypogonadism
-
The Baltimore Longitudinal Study on Aging reported the incidence of total serum T < 325 ng/dL to be 20% for men in their 60s, 30% for men in their 70s and 50% for men over 80
-
The Massachusetts Aging Male Study reported that 12.3% of men aged 40 to 70 had a total serum T of < 200 ng/dL with 3 or more symptoms of hypogonadism
- ...19 more annotations...
-
The Boston Area Community Health Study reported that 5.6% of men aged 30 to 70 were hypogonadal, as defined by total serum T < 300 ng/dL; or, free serum T < 5 ng/dL plus 3 or more symptoms of hypogonadism
-
In a health screening project among 819 men in Taiwan, the prevalence of hypogonadism (total serum T < 300 ng/dL) ranged from 16.5% for men in their 40s, 23.0% for men in their 50s, 28.9% for men in their 60s, and 37.2% for men older than 70 years of age
-
The prevalence of hypogonadism among men in Taiwan is higher than the prevalence reported in the Massachusetts Male Aging Study
-
CAG repeat sequence, within the androgen receptor (AR). Rajender et al[12] reviewed over 30 studies on the AR trinucleotide repeat and infertility
-
suggestion that CAG repeat length may determine androgen responsiveness, this issue is not clearly settled
-
Those in the hypogonadal group (n = 4269) had direct health care costs, that exceeded the eugonadal group (n = 4269) by an average of $7100 over the course of the observation window
-
Meta-analyses of clinical TRT trials as of 2010 have identified three major adverse events resulting from TRT: (1) polycythemia; (2) an increase in prostate-related events; and (3) and a slight reduction in serum high-density lipoprotein (HDL) cholesterol
-
no published analysis has reported measurable increases in prostate cancer risk or Gleason score in men undergoing TRT, or in hypogonadal men with a history of prostate cancer undergoing TRT
-
the prostate which highly expresses the type II 5α-reductase enzyme. Inhibition of this enzyme via finasteride (a type II 5α-reductase inhibitor) or dutasteride (a dual type I and II 5α-reductase inhibitor) reduces circulating DHT 50%-75% and > 90%, respectively[47], and reduces prostate mass[48] and prostate cancer risk
-
Normally estradiol partially regulates testosterone levels, at the hypothalamus, blunting LH and FSH release from the pituitary. As a selective estrogen receptor modulator, CC interrupts this pathway, and consequently there is a greater stimulation for the production of testosterone in Leydig cells
17More
Testosterone for the aging male; current evidence and recommended practice - 0 views
-
Total serum testosterone consists of free testosterone (2%–3%), testosterone bound to sex hormone binding globulin (SHBG) (45%) and testosterone bound to other proteins (mainly albumin −50%)
-
Testosterone binds only loosely to albumin and so this testosterone as well as free testosterone is available to tissues and is termed bioavailable testosterone
- ...13 more annotations...
-
Bioavailable and free testosterone are known to correlate better than total testosterone with clinical sequelae of androgenization such as bone mineral density and muscle strength
-
The reliable measurement of serum free testosterone requires equilibrium dialysis. This is not appropriate for clinical use as it is very time consuming and therefore expensive.
-
With increasing age, a greater number of men have total testosterone levels just below the normal range or in the low-normal range. In these patients total testosterone can be an unreliable indicator of hypogonadal status.
-
It is advised that at least two serum testosterone measurements, taken before 11 am on different mornings, are necessary to confirm the diagnosis.
-
Patients with serum total testosterone consistently below 8 nmol/l invariably demonstrate the clinical syndrome of hypogonadism and are likely to benefit from treatment. Patients with serum total testosterone in the range 8–12 nmol/l often have symptoms attributable to hypogonadism and it may be decided to offer either a clinical trial of testosterone treatment or to make further efforts to define serum bioavailable or free testosterone and then reconsider treatment. Patients with serum total testosterone persistently above 12 nmol/l do not have hypogonadism and symptoms are likely to be due to other disease states or ageing per se so testosterone treatment is not indicated.
-
Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year.
-
With advancing age there is also a reduction in androgen receptor concentration in some target tissues and this may contribute to the clinical syndrome of LOH
-
Gonadotrophin levels rise during aging (Feldman et al 2002) and testicular secretory responses to recombinant human chorionic gonadotrophin (hCG) are reduced
-
There are changes in the lutenising hormone (LH) production which consist of decreased LH pulse frequency and amplitude, (Veldhuis et al 1992; Pincus et al 1997) although pituitary production of LH in response to pharmacological stimulation with exogenous GnRH analogues is preserved
-
the decreases in testosterone levels with aging seem to reflect changes at all levels of the hypothalamic-pituitary-testicular axis
1More
Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pi... - 0 views
1More
Cytokines and steroidogenesis. - PubMed - NCBI - 0 views
1More
LPS-Induced Inflammation Potentiates the IL-1-Mediated Reduction of LH Secretion from t... - 0 views
www.hindawi.com/...926937
inflammation luteinizing hormone LH hypothalamus pituitary Testosterone LPS IL-1beta
shared by Nathan Goodyear on 03 Mar 15
- No Cached
1More
http://www.neuroanatomy.wisc.edu/coursebook/neuro2(2).pdf - 0 views
1More
Central Control of Body Weight and Appetite - 0 views
www.ncbi.nlm.nih.gov/...PMC2585760
adipose tissue appetite satiety Gherlin leptin adiponectin insulin glucagon
shared by Nathan Goodyear on 25 Oct 14
- No Cached
1More
Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocri... - 0 views
1More
Clomiphene citrate effects on testosterone/estroge... [J Sex Med. 2005] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...16422830
clomid HPA low T testosterone estrogen estradiol hypogonadism men male hormone hormones
shared by Nathan Goodyear on 24 Jul 14
- No Cached
-
small cohort with low serum Total Testosterone improved T:E2 ratio with clomid. Clomid restores the HPA through inhibition of the negative feedback of Estradiol on the Hypothalamus and Pituitary in men. This allows for an increase in gonadotropin production and thus increase in testosterone production. Aromatase inhibition therapy would likely still prove beneficial in this situation.
1More
Low testosterone is associated with disability in... [Mult Scler. 2014] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...24710799
low T Testosterone MS multiple Sclerosis hypogonadism men male hormone hormones
shared by Nathan Goodyear on 09 Apr 14
- No Cached
1More
Membrane Estrogen Receptors Stimulate Intracellular Calcium Release and Progesterone Sy... - 0 views
www.jneurosci.org/...12950.full
estradiol estrogen progesterone hypothalamus receptors ER ER-alpha ER alpha hormones CNS astrocytes brain calcium channels
shared by Nathan Goodyear on 10 Mar 14
- No Cached
64More
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...
-
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
-
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
-
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
-
-
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.
-
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
-
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
-
men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat mass is already present before puberty
-
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
-
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
-
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
-
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
-
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
-
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.
38More
Testosterone and glucose metabolism in men: current concepts and controversies - 0 views
-
-
Only 5% of men with type 2 diabetes have elevated LH levels (Dhindsa et al. 2004, 2011). This is consistent with recent findings that the 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
- ...32 more annotations...
-
Consistent with the 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
-
Interestingly, a recent 16-week study of experimentally induced hypogonadism in healthy men with graded testosterone add-back either with or without concomitant aromatase inhibitor treatment has in fact suggested that low oestradiol (but not low testosterone) may be responsible for the hypogonadism-associated increase in total body and intra-abdominal fat mass
-
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
-
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
-
This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
-
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
-
Several observational and randomised studies reviewed in Grossmann (2011) have shown that weight loss, whether by diet or surgery, leads to substantial increases in testosterone, especially in morbidly obese men
-
This suggests that 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
-
successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
-
weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
-
In part, the discrepant results may be due to the fact men in the Vigen cohort (Vigen et al. 2013) had a higher burden of comorbidities. Given that one (Basaria et al. 2010), but not all (Srinivas-Shankar et al. 2010), RCTs in men with a similarly high burden of comorbidities reported an increase in cardiovascular events in men randomised to testosterone treatment (see section on Testosterone therapy: potential risks below) (Basaria et al. 2010), testosterone should be used with caution in frail men with multiple comorbidities
-
The retrospective, non-randomised and non-blinded design of these studies (Shores et al. 2012, Muraleedharan et al. 2013, Vigen et al. 2013) leaves open the possibility for residual confounding and multiple other sources of bias. These have been elegantly summarised by Wu (2012).
-
Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
-
This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
-
it is conceivable that testosterone treatment may have more significant effects on glucose metabolism in uncontrolled diabetes, akin to what has generally been shown for conventional anti-diabetic medications.
-
the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
-
Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
-
the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
-
-
testosterone is inversely associated with total cholesterol, LDL cholesterol and triglyceride (Tg) levels, but positively associated with HDL cholesterol levels, even if adjusted for confounders
-
Although observational studies show a consistent association of low testosterone with adverse lipid profiles, whether testosterone therapy exerts beneficial effects on lipid profiles is less clear
-
Whereas testosterone-induced decreases in total cholesterol, LDL cholesterol and Lpa are expected to reduce cardiovascular risk, testosterone also decreases the levels of the cardio-protective HDL cholesterol. Therefore, the net effect of testosterone therapy on cardiovascular risk remains uncertain.
-
data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
-
compared with otherwise healthy young men with organic androgen deficiency, there may be increased risks in older, obese men because of comorbidities and of decreased testosterone clearance
1More
The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views
www.jneurosci.org/...1448.long
DHT metabolite metabolites 3-beta androstanediol 3-beta-diol HPA stress ER estrogen receptor ER beta ER-beta hormone hormones
shared by Nathan Goodyear on 03 Feb 14
- No Cached
70More
Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Lite... - 0 views
-
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
-
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
-
In patients with CHF, testosterone replacement therapy has been shown to significantly improve exercise tolerance while having no effect on LVEF
- ...66 more annotations...
-
testosterone therapy causes a shift in the skeletal muscle of CHF patients toward a higher concentration of type I muscle fibers
-
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.
-
Lower levels of endogenous testosterone have been associated with longer duration of the QTc interval
-
negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries, abdominal aorta, and thoracic aorta
-
These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.
-
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.
-
The Massachusetts Male Aging Study also projects ≈481 000 new cases of hypogonadism annually in US men within the same age group
-
since 1993 prescriptions for testosterone, regardless of the formulation, have increased nearly 500%
-
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
-
A growing body of evidence suggests that men with lower levels of endogenous testosterone are more prone to develop CAD during their lifetimes
-
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.
-
The biologically inactive form of testosterone is tightly bound to SHBG and is therefore unable to bind to androgen receptors
-
The biologically inactive fraction of testosterone comprises nearly 68% of the total testosterone in human serum
-
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
-
It is estimated that ≈30% of total serum testosterone is bound to albumin, whereas the remaining 1% to 3% circulates as free testosterone
-
it can be argued that using the biologically active form of testosterone to evaluate the association with CAD will produce the most reliable results
-
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
-
patients with catheterization‐proven CAD had statistically significant lower levels of bioavailable testosterone
-
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
-
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
-
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
-
the relative risk of all‐cause mortality in men with lower levels of total testosterone was calculated to be 1.35
-
higher risk of cardiovascular mortality is associated with lower levels of bioavailable testosterone
-
Existing evidence seems to suggest that lower levels of endogenous testosterone are associated with higher rates of all‐cause mortality and cardiovascular mortality
-
studies have shown that lower levels of endogenous bioavailable testosterone are associated with higher rates of all‐cause and cardiovascular mortality
-
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
-
In more recent studies, 3 randomized, placebo‐controlled trials demonstrated that administration of testosterone improves myocardial ischemia in men with CAD
-
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.
-
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
-
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
-
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
-
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.
-
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
-
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
-
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
-
Existing evidence strongly suggests that the levels of total and free testosterone are lower among diabetic patients compared with those in nondiabetics
-
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
-
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.
-
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
-
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
-
Intima‐media thickness (IMT) of the carotid artery is considered a marker for preclinical atherosclerosis
-
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
-
1 study has demonstrated that lower levels of free testosterone are associated with accelerated progression of carotid artery IMT
-
another study has reported that decreased levels of total and bioavailable testosterone are associated with progression of atherosclerosis in the abdominal aorta
-
These findings suggest that normal physiologic testosterone levels may help to protect men from the development of atherosclerosis
-
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
-
Type I muscle fibers, also known as slow‐twitch or oxidative fibers, are associated with enhanced strength and physical capability
-
It has been shown that those with advanced CHF have a higher percentage of type II muscle fibers, based on muscle biopsy
-
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.
-
Testosterone replacement therapy has been shown to significantly improve exercise capacity, without affecting LVEF
-
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
-
Data from 3 meta‐analyses seem to contradict the commonly held belief that testosterone administration may increase the risk of developing prostate cancer
-
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
-
the existing data from the 3 meta‐analyses seem to indicate that testosterone replacement therapy does not increase the risk of adverse cardiovascular events
-
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
-
-
-
the studies that failed to find an association between testosterone and CRP used an older population group
-
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
-
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.