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Are major risk factors for myocardial infarction the major
predictors of degree of coronary artery disease in men?
Although
numerous cross-sectional studies have reported associations of hypertension,
hypercholesterolemia, diabetes, smoking, and/or obesity with the presence of
coronary artery disease (CAD), correlations of these risk factors for myocardial
infarction (MI) with the degree or progression of CAD have been less consistent.
Nevertheless, these risk factors are generally assumed to be major determinants
not only of MI, but of the degree of CAD as well. The present study is an attempt
to evaluate the relationship of major risk factors for MI to degree of CAD.
From 182 men who underwent diagnostic coronary arteriography, the 154 with
CAD were selected for study. These 154 patients were divided into 2 groups,
those with hypertension, hypercholesterolemia, diabetes, smoking, and/or obesity
(n = 121) and those with none of these risk factors (n = 33). The mean degree
of CAD in the group with risk factors for MI (44.4%) and in the group without
(50.6%) was not significantly different (P =.15); nor was the increase in CAD
with age augmented by the presence of these risk factors. On multiple regression
analysis, none of these risk factors was associated with degree of CAD. Three
other variables that were considered in this study, age, high-density lipoprotein-cholesterol
(HDL-C), and free testosterone (FT), did show an independent association with
degree of CAD. These findings, together with the findings of previous studies
from other laboratories, raise the possibility that in men selected for coronary
arteriography, age, HDL-C, and FT may be stronger predictors of degree of CAD
than are blood pressure, cholesterol, diabetes, smoking, and body mass index
(BMI).
Metabolism. 2004 Mar;53(3):324-9
Endogenous sex hormones and progression of carotid atherosclerosis
in elderly men.
BACKGROUND: The burden of atherosclerosis
especially afflicts the increasing older segment of the population.
Recent evidence has emphasized a protective role of endogenous sex
hormones in the development of atherosclerosis in aging men. METHODS
AND RESULTS: We studied the association between endogenous sex hormones
and progression of atherosclerosis in 195 independently living elderly
men. Participants underwent measurements of carotid intima-media thickness
(IMT) at baseline in 1996 and again in 2000. At baseline, serum concentrations
of testosterone (total and free) and estradiol (total and free E2) were measured.
Serum free testosterone concentrations were inversely related to the mean progression
of IMT of the common carotid artery after adjustment for age (beta=-3.57; 95%
CI, -6.34 to -0.80). Higher serum total and free E2 levels were related to
progression of IMT of the common carotid artery after adjustment for age (beta=0.38;
95% CI, -0.11 to 0.86; and beta=0.018; 95% CI, -0.002 to 0.038, respectively).
These associations were independent of body mass index, waist-to-hip ratio,
presence of hypertension and diabetes, smoking, and serum cholesterol levels
CONCLUSIONS: Low free testosterone levels were related to IMT of the common
carotid artery in elderly men independently of cardiovascular risk factors.
Circulation. 2004 May 4;109(17):2074-9. Epub 2004 Apr 19
The associations of endogenous testosterone and sex hormone-binding
globulin with glycosylated hemoglobin levels, in community dwelling
men. The Tromso Study.
OBJECTIVES: Low levels of endogenous testosterone have been associated with
increased risk of cardiovascular disease and atherosclerosis in men. Long-term
hyperglycemia, as measured by glycosylated hemoglobin (HbA1c), is related to
cardiovascular mortality, and HbA1c across its normal range is also positively
related to coronary heart and cardiovascular disease mortality in men. We therefore
undertook an analysis of the cross-sectional associations of total testosterone
and SHBG levels with HbA1c levels, in a general population of 1419 men aged
25-84.METHODS: Total testosterone, sex hormone-binding globulin (SHBG) and
HbA1c were measured by immuno-assay. Partial correlation and multiple regression
analyses were used to estimate the associations between total testosterone
and SHBG with HbA1c. Analyses of variance and covariance were used to compare
men with or without diabetes.RESULTS: In age-adjusted partial correlation HbA1c
was inversely associated with total testosterone (p<0.01) and SHBG (p<0.001).
HbA1c was positively associated with body mass index (BMI) and waist circumference
(WC) (p<0.001). In multiple regression analyses total testosterone, SHBG,
age, number of cigarettes smoked, BMI and WC were independently associated
with HbA1c levels. Men with a history of diabetes had lower levels of total
testosterone in age-adjusted analyses (p<0.05) and lower levels of SHBG
in both age- and WC-adjusted analyses (p<0.001 and p<0.01, respectively).CONCLUSION:
Lower levels of total testosterone and SHBG were associated with increased
HbA1c levels and diabetes independent of concomitant variations in obesity
and body fat distribution.
Diabetes Metab. 2004 Feb;30(1):29-34
An assessment of correlations between endogenous sex hormone
levels and the extensiveness of coronary heart disease and the ejection
fraction of the left ventricle in males.
This clinical study investigated the possible associations of male sex hormone
with the extensiveness of coronary artery lesions, coronary heart disease risk
factors and ejection fraction of the heart. Ninety six Caucasian male subjects
were recruited, 76 with positive and 20 with negative coronary angiograms.
Early morning, prior to haemodynamic examination all of them had determined
levels of total testosterone, free testosterone, free androgen index (FAI),
sex hormone-binding globulin (SHBG), oestradiol, luteinizing hormone, follicle-stimulating
hormone, plasma lipids, fibrinogen and glucose. The ejection fraction and the
extensiveness of coronary lesions of each subject was assessed on the basis
of x-ray examination results using Quantitative Coronary Angiography (QCA)
and Left Ventricular Analysis (LVA) packages on the TCS Acquisition workstation,
Medcon. Men with proven coronary heart disease had significantly lower levels
of total testosterone (11.9 vs 21.2 nmol/l), free testosterone (45.53 vs 86.10
pmol/l), free androgen index (36.7 vs 47.3 IU) and oestradiol (109.4 vs 146.4
pmol/l). The level of testosterone was negatively associated with the DUKE
Index. The most essential negative correlation was observed between SHBG and
atherogenic lipid profile (low high-density lipoprotein, high triglycerides).
Ejection fraction was substantially lower in patients (51.85 vs 61.30) (without
prior myocardial infarction) with low levels of free-testosterone (23.85 vs.
86.10 pmol/l) and FAI (28.4 vs 47.3 IU). A negative correlation was observed
between total testosterone, free testosterone, FAI and blood pressure, especially
with diastolic pressure. Men with proven coronary atherosclerosis had lower
levels of endogenous androgens than the healthy controls. For the first time
in clinical settings it has been demonstrated that low levels of free-testosterone
was characteristic for patients with low ejection fraction. Numerous hypothesies
for this action can be proposed but all require a proper evaluation process.
The main determinant of atherogenic plasma lipid was low levels of SHBG suggesting
its main role in developing atheroscerotic lesions.
J Med Invest. 2003 Aug;50(3-4):162-9
Acute haemodynamic effects of testosterone in men with chronic
heart failure.
AIMS: Anabolic therapy with testosterone may be useful in the treatment of
wasting associated with chronic heart failure but little is known about its
cardiovascular actions. The aim of this study was to determine the acute haemodynamic
effects of testosterone administration in men with heart failure. METHODS AND
RESULTS: Twelve men with stable chronic heart failure were enrolled in a double-blind,
randomised, placebo-controlled, cross-over trial. Subjects were given testosterone
60 mg or placebo via the buccal route and central haemodynamics were monitored
over 6h, using a pulmonary flotation catheter. Subjects received the second
treatment on day 2 and haemodynamic monitoring was repeated. Treatment was
well tolerated. Compared with placebo, testosterone treatment resulted in a
relative increase in cardiac output (p<0.0001, ANCOVA), with maximum treatment
effect after 180 min (10.3+/-4.6% increase from baseline, p=0.035; 95% CI 0.8-19.8).
This was accompanied by reduction in systemic vascular resistance compared
with baseline (p<0.0001, ANCOVA), with maximum treatment effect also at
180 min (-17.4+/-9.6% from baseline, p=0.085; 95% CI -37.3 to +2.6). These
maximal changes coincided with the peak elevation in serum bio-available testosterone.
There was no significant change in any other haemodynamic parameter measured.
CONCLUSIONS: Administration of testosterone increases cardiac output acutely,
apparently via reduction of left ventricular afterload.
Eur Heart J. 2003 May;24(10):909-15
Administration of testosterone is associated with a reduced
susceptibility to myocardial ischemia.
This study investigated the impact of testosterone on myocardial ischemia-reperfusion
injury and corresponding intracellular calcium ([Ca2+]i) metabolism. Nonorchiectomized
mature male Wistar rats were randomly assigned to placebo, a single dose of
testosterone undecanoate, or 5alpha-dihydrotestosterone. In a further series,
orchiectomized rats were treated with placebo. After 2 wk of treatment, the
hearts were removed and placed in a Langendorff setup. The isolated, buffer-perfused
hearts were subjected to 30 min of no-flow ischemia and 30 min of reperfusion.
Recovery of myocardial function was measured by analyzing pre- and postischemic
left ventricular ( LV) systolic/diastolic pressure and coronary perfusion pressure
simultaneously, together with [Ca2+]i handling (aequorin luminescence). Calcium
regulatory proteins were analyzed by Western blotting. LV weight/body weight
ratio was increased after administration of testosterone vs. orchectomized
rats. The recovery of contractile function was improved in testosterone-treated
rats: at the end of the reperfusion, LV systolic pressure was higher and end-diastolic
pressure was lower in testosterone-treated rats. End-ischemic [Ca2+]i and [Ca2+]i
overload upon reperfusion was significantly lower in testosterone vs. orchiectomized
rats, too. However, levels of calcium regulatory proteins remained unaffected.
In conclusion, administration of testosterone significantly improves recovery
from global ischemia. These beneficial effects are associated with an attenuation
of reperfusion induced [Ca2+]i overload.
Endocrinology. 2003 Oct;144(10):4478-83. Epub 2003 Jul 10
High levels of circulating testosterone are not associated
with increased prostate cancer risk: a pooled prospective study.
Androgens
stimulate prostate cancer in vitro and in vivo. However, evidence
from epidemiologic studies of an association between circulating levels
of androgens and prostate cancer risk has been inconsistent. We investigated
the association of serum levels of testosterone, the principal androgen
in circulation, and sex hormone-binding globulin (SHBG) with risk
in a case-control study nested in cohorts in Finland, Norway and Sweden
of 708 men who were diagnosed with prostate cancer after blood collection
and among 2,242 men who were not. In conditional logistic regression
analyses, modest but significant decreases in risk were seen for increasing
levels of total testosterone down to odds ratio for top vs. bottom
quintile of 0.80 (95% CI = 0.59-1.06; p(trend) = 0.05); for SHBG,
the corresponding odds ratio was 0.76 (95% CI = 0.57-1.01; p(trend)
= 0.07). For free testosterone, calculated from total testosterone
and SHBG, a bell-shaped risk pattern was seen with a decrease in odds
ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60-1.14; p(trend)
= 0.44). No support was found for the hypothesis that high levels of
circulating androgens within a physiologic range stimulate development
and growth of prostate cancer.
Int J Cancer. 2004 Jan 20;108(3):418-24
Reduced circulating androgen bioactivity in patients with
prostate cancer.
BACKGROUND: Previous studies on immunoreactive androgen levels in serum have
revealed equivocal associations with the risk of prostate cancer (CaP). The
aim of this study was to compare serum biological androgen activity between
men with newly diagnosed CaP and age-matched men with benign prostatic hyperplasia
(BPH). METHODS: Caucasian men with newly diagnosed, untreated CaP (n = 101)
and age-matched patients with BPH (n = 103) were investigated. Serum androgen
bioactivity ( ABA) levels were measured using a recently developed recombinant
cell bioassay. RESULTS: In comparison to men with BPH, CaP patients with Gleason
score >or=8 (n = 16) had lower serum ABA (P < 0.05), and patients with
Gleason score <or=5 (P < 0.05) or >or=8 (P = 0.07) displayed suppressed
ABA levels in relation to serum testosterone. As the entire group, men with
CaP (n = 101) had significantly lower serum ABA than age-matched men with BPH
(n = 103): median 3.0 nM (range, 0.8-6.4 nM) versus 3.2 nM (range, 0.8-7.9
nM) testosterone equivalents, respectively (P < 0.005). By contrast, serum
immunoreactive testosterone and SHBG concentrations and free androgen indices
did not differ significantly between the two groups. CONCLUSIONS: Patients
with CaP have lower serum ABA than controls with BPH, and men with low or high
Gleason score display suppressed circulating ABA-to-testosterone ratio. These
features may reflect interaction between variables such as the degree of tumor
differentiation and tumor volume with androgen metabolism.
Prostate. 2003 May 15;55(3):194-8
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