study looked at androgen deprivation therapy in non-metastatic prostate cancer. This study found that the elimination of ADR post 5 years was associated with low recurrence. Relapse of increased PSA was associated with increasing Testosterone off of ADR. This study did not look at estrogens or androgen metabolites. Too short sided in its design.
Small study of young men, average age 24.5, found a 10-15% reduction in Testosterone levels with 1 week of sleep deprivation. Sleep was reduced to 5 hours per night for just 1 week.
Sleep deprivation, defined as 1 night of no sleep, changed epigenetic expression of BMAL via increased methylation. Other findings: decreased cortisol, increased glucose...
The process of androgen deprivation therapy needs to be re-evaluated. Why? First, the CVD side effects associated with the androgen depletion. Second, the depletion of 3 beta androstanediol that has been shown to bind to ER beta and inhibit growth. As in this study that finds that ER beta activity slows prostate cancer through destabilizing of HIF-1 alpha and by inhibiting VEGF.
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
The presence of symptoms was more closely linked to increasing age than to testosterone levels
Findings similar to type 2 diabetes were reported for men with the metabolic syndrome, which were associated with reductions
in total testosterone of −2.2 nmol/l (95% CI −2.41 to 1.94) and in free testosterone
low testosterone is more predictive of the metabolic syndrome in lean men
Cross-sectional studies uniformly show that 30–50% of men with
type 2 diabetes have lowered circulating testosterone levels, relative to references based on healthy young men
In a recent cross-sectional study of 240 middle-aged men (mean age 54 years) with either type 2 diabetes, type 1 diabetes
or without diabetes (Ng Tang Fui et al. 2013b), increasing BMI and age were dominant drivers of low total and free testosterone respectively.
both diabetes and the metabolic syndrome are associated with a modest reduction in testosterone, in magnitude comparable
with the effect of 10 years of ageing
In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone
with anaemia
In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
probably the most important point made in this article
low testosterone identifies men with an adverse metabolic phenotype
Diabetic men with low testosterone are significantly more likely to be obese or insulin resistant
increased inflammation, evidenced by higher CRP levels
Bioavailable
but not free testosterone was independently predictive of mortality
It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker,
co-existing because of in-common risk factors.
In prospective studies, reviewed in detail elsewhere (Grossmann et al. 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone
compared with total testosterone
In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident
metabolic syndrome
low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
In cross-sectional studies of men with (Grossmann et al. 2008) and without (Bonnet et al. 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control
SHBG may have biological actions
beyond serving as a carrier protein for and regulator of circulating sex steroids
In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
expensive, laborious process filled with variables
Low free testosterone remains inversely associated with insulin resistance, independent of SHBG (Grossmann et al. 2008). This suggests that the low testosterone–dysglycaemia association is not solely a consequence of low SHBG.
Experimental evidence reviewed below suggests that visceral adipose tissue is an important intermediate (rather than a
confounder) in the inverse association of testosterone with insulin resistance and metabolic disorders.
testosterone promotes the commitment of
pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
testosterone regulates the metabolic functions
of mature adipocytes (Xu et al. 1991, Marin et al. 1995) and myocytes (Pitteloud et al. 2005) in ways that reduce insulin resistance.
Pre-clinical evidence (reviewed in Rao et al. (2013)) suggests that at the cellular level, testosterone may improve glucose metabolism by modulating the expression of the glucose-transported
Glut4 and the insulin receptor, as well as by regulating key enzymes involved in glycolysis.
More recently testosterone has
been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
Interestingly, a reciprocal feedback also appears to exist, given that not only chronic (Cameron et al. 1990, Allan 2013) but also, as shown more recently (Iranmanesh et al. 2012, Caronia et al. 2013), acute hyperglycaemia can lower testosterone levels.
There is
also evidence that testosterone regulates insulin sensitivity directly and acutely
In men with prostate cancer commencing androgen deprivation therapy, both total as well as, although not in all studies (Smith 2004), visceral fat mass increases (Hamilton et al. 2011) within 3 months
More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several
large observational registry studies
Testosterone has also been shown to reduce the concentration of pro-inflammatory cytokines in some, but not all studies, reviewed
recently in Kelly & Jones (2013). It is not know whether this effect is independent of testosterone-induced changes in body composition.
the observations discussed in this section suggest that it is the decrease in testosterone that causes insulin
resistance and diabetes. One important caveat remains: the strongest evidence that low testosterone is the cause rather than
consequence of insulin resistance comes from men with prostate cancer (Grossmann & Zajac 2011a) or biochemical castration, and from mice lacking the androgen receptor.
Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the
age-related decline in testosterone levels
there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in
testosterone
Circulating testosterone, on an average 30%, is lower in obese compared with lean men
increased visceral fat is an important component in the association of low testosterone and insulin resistance
The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone
levels
obesity is a dominant
risk factor
men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat
mass is already present before puberty
Only 5% of men with type 2 diabetes have elevated LH levels
inhibition of the gonadal axis predominantly takes place in the hypothalamus,
especially with more severe obesity
Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin
are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH)
secretion from GNRH neurons situated in the preoptic area
kisspeptin has emerged as one of the
most potent secretagogues of GNRH release
hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression
of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility,
LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity
independent of body weight, whereas oestradiol withdrawal had no effects
suppression of the diabesity-associated HPT axis is functional, and may hence be
reversible
Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
weight gain and development
of diabetes accelerate the age-related decline in testosterone
Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone
levels than age alone
55% of symptomatic androgen deficiency reverted to a normal testosterone or an asymptomatic state after 8-year follow-up,
suggesting that androgen deficiency is not a stable state
Weight loss can reactivate the hypothalamic–pituitary–testicular axis
Leptin treatment resolves hypogonadism in leptin-deficient men
The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen
receptor modulators in obese men
Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men
with type 2 diabetes
change in BMI was associated with the change in testosterone (Corona et al. 2013a,b).
weight loss can lead to genuine reactivation
of the gonadal axis by reversal of obesity-associated hypothalamic suppression
There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
in men who improved their glycaemic control over time, testosterone levels increased. By
contrast, in those men in whom glycaemic control worsened, testosterone decreased
testosterone levels should be measured after successful weight loss to identify men with an insufficient rise
in their testosterone levels. Such men may have HPT axis pathology unrelated to their obesity, which will require appropriate
evaluation and management.
Article discusses the the conversion of 3-alpha-diol back to DHT and this role in prostate cancer in androgen deprivation therapy. What we now know is that this metabolite interacts with ER alpha receptor to promote proliferation. Carcinogenesis appears to be primarily an estrogen driven process and her in prostate cancer, the androgen metabolites are promoting proliferation through estrogen receptors.
Chemical castration as seen in androgen deprivation therapy resulted in precipitous decline in Testosterone and Estradiol in men. Associated increased in beta-amylloid found.
Androgen deprivation therapy leads to insulin resistance, metabolic syndrome, and type II diabetes in men. Testosterone therapy in men with IR, obesity, metabolic syndrome, and type II Diabetes will result in improved cardiovascular risk.
This article focus' more on the risks of colorectal cancer in men. It does perform a mini-review on risks for women. It appears progesterone is important in prevention of colorectal cancer in women. Post-menopause, women with HRT have a reduced risk. In contrast, men with androgen deprivation therapy, there is an increase risk of colorectal cancer.
Sometimes I think medicine has lost its mind. Or at least, it is not thinking things through. To give IV estrogen to decrease Testosteorne in men with prostate cancer is devoid of the pathophysiology of prostate cancer and cardiovascular disease in men. Elevated Estradiol in men increases CRP, IL-1beta, and TNF-alpha to name a few cytokines. The proported purpose of the IV estrogen is to prevent the cardiovascular complications associated with ADT. Yet, elevated aromatase activity and low T in men are both shown to be associated with increased CVD in men.
We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
RAS, PI3K, TP53 and MYC
The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure (Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure (Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
glutamine consumption associated with parallel increases in glutamate and aspartate (Figure (Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
these metabolic disturbances would be expected to remain extant after therapeutic interventions
accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
The switch may also involve down-regulation of endogenous inhibitors of angiogenesis such as endostatin, angiostatin or thrombospondin (reviewed in [5]) and has thus been regarded as the result of tipping the net balance between positive and negative regulators
There is a complex interrelationship between tumor hypoxia and tumor angiogenesis
Environmental stress as a result of low oxygen and proper nutrient deprivation, such as glucose deprivation, are capable of inducing VEGF mRNA stabilization resulting in increased levels of the secreted ligand and angiogenic growth
HIFalpha subunits accumulate in the cytoplasm where they bind HIFbeta to form a heterodimer that subsequently translocates to the nucleus to activate transcription of target genes, including genes important for various processes such as metabolism (glucose transporter (GLUT)-1, hexokinase (HK)-1), cell growth (cyclin (CCN)-D1 [23]) and also angiogenesis, such as erythropoietin, VEGF and PDGF [24] (summarized in Fig. 1)
When oxygen levels are low (hypoxia; red arrow) PHDs cannot hydroxylate HIFalphas thereby allowing them to escape pVHL-mediated degradation. HIFalpha subunits accumulate and bind to their heterodimeric partner, HIFbeta, translocate into the nucleus and activate a cascade of hypoxic signaling first by the transcription of various target genes including microRNAs that are important for tumor promoting pathways
c-Src is also capable of activating HIFs by indirectly inhibiting PHD activity via the NADPH oxidase/Rac pathway.
mTOR can also promote stabilization and HIF transcriptional activity
hypoxia inducible factors (HIFs), heterodimeric transcription factors composed from alpha and beta subunits, which can be rapidly stabilized to fluidly adapt to and overcome the effects of a hypoxic environment
Curcumin inhibits the expression of epidermal growth factor receptor (EGFR), VEGFR-1, VEGFR-2 and VEGFR-3, and the kinase activity of Src and FAK, which are responsible for the induction of angiogenic genes as well as endothelial cell polarity and migration
Curcumin also reduces the MMP-2 and MMP-9 expression, along with the suppression of growth and invasion potential of tumor cells in culture and xenograft experiments
The expression of angiogenic biomarkers COX-2 and serum levels of VEGF were significantly reduced in the curcumin-treated group
Resveratrol inhibits capillary endothelial cell growth and new blood vessel growth in animals
[155] and impeding angiogenesis by suppressing VEGF expression through down-regulation of HIF-1alpha
resveratrol was reported to inhibit cell proliferation of human ovarian cancer cells and human osteosarcoma cells by attenuating HIF-1alpha
prevents cytokine-induced vascular leakage and tumor metastasis
The underlying molecular mechanisms include: blocking VEGF- and FGF-receptor-mediated MAPK activation, inhibiting Akt- and MAPK-driven HIF-1alpha basal expression and its induction by IGF-1, stimulating the proteasomal degradation of HIF-1alpha, inhibiting phosphatidyl inositol (PI)-3K/Akt and Ras/mitogen/extracellular signal-regulated kinase (MEK)/ERK pathways, and activation of forkhead box (FOX)O transcription factors
"Cells are more responsive and sensitive to heat under oxygen-deprived and highly acidic conditions, which are common in cancer tissue due to aggressive growth and enhanced glycolysis"
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Testosterone has beneficial
effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves
cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart
failure.
testosterone is an L-calcium channel blocker and induces potassium
channel activation in vascular smooth muscle cells
Animal studies have consistently demonstrated that testosterone is atheroprotective,
whereas testosterone deficiency promotes the early stages of atherogenesis
there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes
adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
bidirectional effect between decreased testosterone
concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and
insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular
risk factors
Achieving a normal physiological testosterone concentration through the administration
of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central
adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory
profiles and vascular function
It is well known that impaired erectile function and CVD are closely
related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5
years
no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
free testosterone
levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated
brachial artery vasodilation in men with CAD
Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects
when testosterone is replaced within normal physiological limits in humans
Endothelium-independent mechanisms of testosterone
are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
Testosterone shares the same molecular binding site as nifedipine
Testosterone increases the expression of endothelial nitric oxide synthase (eNOS)
and enhances nitric oxide (NO) production
Testosterone also inhibited
the Ca2+ influx response to PGF2α
one of the major actions of testosterone is on NO and its signalling pathways
In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult
to delineate and may be dependent upon the stage of plaque development
Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate
with serum testosterone
t long-term testosterone treatment reduced CIMT in men with low testosterone levels
and angina
neither intracellular nor membrane-associated
ARs are required for the rapid vasodilator effect
acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described,
primarily in the context of vascular tone regulation via the modulation of gene transcription
Testosterone and DHT increased the expression of eNOS in HUVECs
oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase
inhibition
non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated
human umbilical vein endothelial cells
Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure
in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis
factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM
and/or hypogonadism
patients with the
highest IL1β concentrations had lower endogenous testosterone levels
TRT has been reported to significantly
reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
testosterone treatment to normalise levels in hypogonadal men with the MetS
resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly
men
Higher levels of serum adiponectin have been shown to lower cardiovascular risk
Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ
(IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types
including human endothelial cells
decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in
human endothelial cells when treated with DHT
The key to unravelling the link between testosterone
and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors
and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
testosterone
functions through the AR to modulate adhesion molecule expression
pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
DHT inhibited NFκB activation
DHT could inhibit an LPS-induced upregulation of MCP1
Both NFκB and
AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory
agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis
may reduce or alter any potentially protective effects of testosterone
DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional
level, suggesting that androgens down-regulate IFN-induced genes
(Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT
3β-derivative, 3β-Adiol
TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly
reduced by a pre-incubation with 3β-Adiol in HUVECs
3β-Adiol also reduced LPS-induced gene expression
of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory
effects that are mediated by ER activation.
The authors suggest that DHT differentially
effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and
via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated
an increased risk of adverse cardiovascular events or mortality
The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely
as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase
in either cardiovascular events or mortality in studies up to 12 months
Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse
effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect
or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors,
there may possibly be a cardioprotective action
The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen
and/or disease status.
the majority of studies suggest that testosterone may display both acute and
chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via
endothelium-dependent and -independent mechanisms