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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of metabolic syndrome is increasing globally and is an important risk factor for the development of cardiovascular disease. Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid and aortic atherosclerosis. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity, insulin sensitivity, glycaemic control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. The effect of testosterone therapy on atherogenesis in men is unknown; however, animal studies have shown that testosterone is atheroprotective and can ameliorate the degree of atherosclerosis. Testosterone is an arterial vasodilator and has been shown to improve myocardial ischaemia in men with coronary artery disease. This review discusses the role that testosterone may play in the pathogenesis of metabolic syndrome in men and also examines the potential role of testosterone replacement therapy in this condition.
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PMID:Androgen deficiency as a predictor of metabolic syndrome in aging men: an opportunity for intervention? 1844 1

The traditional lipid profile differs by sex hormone levels. However, associations of sex hormones with lipoprotein subfractions, which may more accurately represent metabolic pathways to atherosclerosis, are not well studied. We quantified the cross-sectional associations of endogenous sex hormones with lipoprotein subfractions in 3143 men and 2038 postmenopausal women who were not on hormone replacement therapy, aged 45 to 84 years, in the Multi-Ethnic Study of Atherosclerosis baseline examination. Particle sizes and numbers of very low-density (VLDL), low-density (LDL), and high-density (HDL) lipoproteins were measured by nuclear magnetic resonance. In both men and women, after multivariable adjustment, higher sex hormone binding globulin (SHBG) levels are associated with smaller, fewer VLDL; larger, fewer LDL; and larger, more numerous HDL particles, whereas higher endogenous estradiol levels are associated with smaller VLDL and smaller, more numerous HDL and LDL particles (all P < .05). Testosterone (adjusted for SHBG) is associated with smaller VLDL particles in men but not women (sex difference P = .040). Higher dehydroepiandrosterone levels are associated with more numerous, smaller VLDL particles only in women (sex difference P = .030, .004, respectively). In conclusion, we found sex differences in the association of endogenous androgens with lipoprotein particle sizes and numbers. Higher endogenous estradiol, but lower SHBG, is associated with a more atherogenic lipoprotein particle profile. These findings highlight the potential to improve the lipoprotein profile with sex hormones, but emphasize the intricacies of the interactions.
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PMID:The association of endogenous sex hormones with lipoprotein subfraction profile in the Multi-Ethnic Study of Atherosclerosis. 1850 60

Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women. Changes in endothelial function play an important role in the pathophysiology of atherosclerosis, and evidence suggests that interventions to improve endothelial function could modify the rates of progression and the risk of cardiovascular events. In addition, a positive association between markers of endothelial dysfunction and androgenicity has been described in women with polycystic ovary syndrome, suggesting a correlation with the early-onset endothelial dysfunction found in these patients. We performed a cross-sectional study to verify whether endogenous testosterone levels are correlated with markers of inflammation and endothelial function and with anthropometric and metabolic profile in 53 postmenopausal women. Serum testosterone, sex hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1 (ET-1) were determined. Patients were stratified into 2 groups (higher or lower than the mean testosterone levels of the studied sample). Mean age was 55 years (+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8 years). Body mass index and waist circumference were significantly higher in the group with testosterone levels >or=0.49 ng/mL. Median CRP levels were greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17 [0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P = .023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed. This association was dependent on homeostasis model assessment index for ET-1 but not CRP. Testosterone was also associated with waist circumference and blood pressure (P = .001). These data suggest that endogenous testosterone levels in recently postmenopausal women may be part of a proatherogenic profile. Longitudinal studies are needed to assess if androgenicity represents a risk factor for cardiovascular disease and the clinical relevance of its association with ET-1 and CRP in this population.
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PMID:Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women. 1855 38

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter-dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.
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PMID:Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone. 1960 30

The strongest independent risk factors for coronary artery disease (CAD) are increasing age and male gender. Whilst a wide variation in CAD mortality exists between countries, a male to female ratio of approximately 2:1 is consistently observed. These observations have led to the assumption that testosterone may exert a detrimental influence on the cardiovascular system. Despite this, coronary atherosclerosis increases with age, whilst a marked fall in serum bioavailable testosterone levels is observed. Similarly, low testosterone levels are also associated with other cardiovascular risk factors and increased expression of mediators of the atherosclerotic process. This in itself suggests that testosterone does not promote atheroma formation. Moreover, epidemiological studies show an inverse relationship between testosterone levels and surrogate markers of atherosclerosis, which suggests that it may be a testosterone deficient state, rather than male sex which is associated with CAD. In cholesterol-fed animal models, atherosclerosis is accelerated by castration and reduced after testosterone replacement therapy. Testosterone has also been shown to improve myocardial ischemia in men with angina pectoris. Consequently, increasing evidence suggests that the process of atherosclerosis is beneficially modulated by testosterone. These studies are the focus of this chapter.
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PMID:Testosterone and coronary artery disease. 1901 Dec 91

Although animal studies support the hypothesis that androgenic biological actions may affect experimental atherosclerosis progression, evidence for a relationship between androgen effects and peripheral arterial disease (PAD), a common clinical form of atherosclerosis, is weak or contradictory. Testosterone, the main androgen hormone, is converted in a 5alpha-reduced form by enzymatic activities in the target cells and some specific actions are mediated by such metabolites. Steroid 5-alpha reductase isoenzymes (SRD5A1 and SRD5A2) catalyze the conversion to the bioactive potent androgen dihydrotestosterone and other reduced metabolites and represent relevant regulators of local hormonal actions. In the present study we tested for the association of selected single nucleotide polymorphisms (SNP) of SRD5A1 and SRD5A2 with symptomatic PAD patients. Two different SNP in the SRD5A1 were significantly associated which the PAD phenotype (p<0.03, odds ratio 1.73), while no association was found between PAD phenotypes and SRD5A2. Since the examined SRDA1 gene variant was previously associated with a low enzymatic activity, we suggest that a decreased local enzymatic conversion of testosterone may contribute to PAD genetic susceptibility.
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PMID:Polymorphisms of steroid 5-alpha-reductase type I (SRD5A1) gene are associated to peripheral arterial disease. 1924 76

Over the last three decades it has become apparent that testosterone plays a significant role in the maintenance of bone and muscle mass, in erythropoiesis, and in mental functions. But testosterone is also a key player in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to late onset diabetes mellitus, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, glucose intolerance, raised blood pressure and dyslipidaemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol),and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin(SHBG) predict a higher incidence of the metabolic syndrome. There is now evidence to argue that hypotestosteronaemia should be an element in the definition of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses the unfavorable risk profile for the development of diabetes and atherosclerosis. Testosterone should be regarded as a pivotal hormone for men's health.
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PMID:The role of testosterone in the metabolic syndrome: a review. 1944 34

Obesity has become a major health problem. Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a proinflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.
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PMID:The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. 2084 93

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.
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PMID:Androgen receptor-dependent and independent atheroprotection by testosterone in male mice. 2086 Dec 31

The role of sex steroid hormones in modulating vascular function in men is of great importance, given that androgen deficiency is strongly associated with common medical conditions including metabolic syndrome, obesity, diabetes, hypertension and atherosclerosis. Testosterone deficiency afflicts approximately 30% of men ages 40-79 years. Testosterone replacement in deficient men with such co-morbidities ameliorates or partially reverses their progression. Studies in animal and humans suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Emerging evidence indicates that androgens may provide a protective effect against the development and/or progression of atherosclerosis in men.
Atherosclerosis 2011 Feb
PMID:Testosterone and cardiovascular disease: an old idea with modern clinical implications. 2086 58


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