Low Serum Testosterone and High Serum Estradiol Associate With Lower Extremity Peripheral Arterial Disease in Elderly Men

Tivesten, Åsa; Mellström, Dan; Jutberger, Hans; Fagerberg, Björn; Lernfelt, Bodil; Orwoll, Eric; Karlsson, Magnus K.; Ljunggren, Östen; Ohlsson, Claes

doi:10.1016/j.jacc.2007.04.088

Cited by 108 publications

(73 citation statements)

References 37 publications

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“…In fact, estradiol and testosterone showed independent opposite associations with HDL-cholesterol in our analysis. These data suggest differential effects of estradiol and testosterone on lipid profile in men and are in agreement with the reported reverse trend in associations between each of the sex steroids and terminal manifestations of cardiovascular disease (11). Although testosterone is the major precursor of estradiol in men (21), the ultimate concentrations of the latter are largely dependent on interindividual variation in several endogenous [enzymatic activity of aromatase (18) and estrogen degrading catechol-Omethyltransferase (17)] as well as exogenous factors.…”

Section: Discussionsupporting

confidence: 82%

“…Circulating concentrations of LDL-cholesterol and HDL-cholesterol in adolescence are good predictors of lipid profile (25) and vascular phenotype (including arterial stiffness and subclinical atherosclerosis) in the adulthood (26)(27). Given that estradiol level shows little variation with age in men (28), its associations with lipids are likely to track into adulthood and may explain observed correlations between estrogens and the terminal manifestations of atherosclerosis in middle-age and elderly men (11,(13)(14)(15). Future long-term prospective studies on estrogens and cardiovascular risk factors are needed to provide a direct verification of our cross-sectional observations.…”

Section: Discussionmentioning

confidence: 99%

“…However, several investigations have shown protective rather than detrimental effects of endogenous testosterone on cardiovascular system, at least in elderly men (8)(9)(10). Consistently, in the majority of studies low circulating concentrations of testosterone have been associated with terminal manifestations of atherosclerosis such as peripheral arterial disease (PAD) (11), ischaemic stroke (12) and coronary artery disease (7). A large body of evidence suggests the opposite effect of estrogens on cardiovascular system in men -increased plasma levels of estradiol have been linked to coronary artery disease (13), higher risk of atherosclerosis (14), PAD (11), and stroke (15).…”

Section: Introductionmentioning

confidence: 95%

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Association between lipid profile and circulating concentrations of estrogens in young men

et al. 2009

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Objectives-Men show higher rates of cardiovascular morbidity and mortality than premenopausal women and this sexual dimorphism may be related to sex-specific effects of sex steroids on cardiovascular risk factors. Unlike androgens, estrogens were not extensively investigated in relation to cardiovascular phenotypes in men.Methods-We examined associations of estradiol and estrone and their precursors (total testosterone and androstenedione) with traditional cardiovascular risk factors (lipids, blood pressure, body mass) in 933 young (median age -19 years), apparently healthy Polish men.Results-Total estradiol was associated with total cholesterol (p=0.006) and HDL-cholesterol (p<0.001) and estrone showed the strongest associations with both total cholesterol (p<0.001) and LDL-cholesterol (p<0.001) in the unadjusted ANOVA analysis. In the multivariable adjusted models in which other independent variables were held as constant one standard deviation increase in estradiol level was associated with 6%-standard deviation increase in total cholesterol (standardized B=0.06, p=0.038) and 6%-standard deviation decrease in p=0.036). An increase in estrone levels by one standard deviation was associated with respective 12%-and 13%-standard deviation increases in total cholesterol (standardized B=0.12, p<0.001) and LDL-cholesterol levels (standardized B=0.12, p<0.001) after controlling for other predictors of lipids. Estrone correlated linearly with androstenedione (r=0.28, p<0.001) but there was no correlation between estradiol and testosterone. Estrogens retained their independent associations with lipids after adjustment for their biochemical precursors in the multivariable analysis.Conclusions-Increased levels of estrogens are associated with unfavourable lipid profile in men and that this association is apparent early in life, before cardiovascular disease manifestations.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Association between lipid profile and circulating concentrations of estrogens in young men

et al. 2009

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“…80,81,97,99 Thus, lower testosterone levels are associated with higher body mass index (BMI), and with increased prevalence and incidence of metabolic syndrome and Type II diabetes in middle-aged and older men. 10,11,13,14,19,[100][101][102][103][104][105][106][107] In addition, lower testosterone levels are associated with surrogate markers for cardiovascular disease, including less favorable carotid intima medial thickness, 108-110 ankle/brachial index as a measure of peripheral arterial disease 111 and calcific aortic atheroma. 112 Thus, Low testosterone levels and ill-health in aging men BB Yeap lower testosterone levels, erectile dysfunction and conditions associated with higher cardiovascular risk appear to be interrelated.…”

Section: Testosterone Cardiovascular Risk and Mortality In Aging Menmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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“…Lower testosterone levels are associated with surrogate markers for cardiovascular disease, including less favorable carotid intima medial thickness [38] ankle/brachial index as a measure of peripheral arterial disease [39] and calcific aortic atheroma [40]. Endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease of all causes.…”

Section: Improving Metabolic Syndrome and Diabetes Type 2 Cardiovascmentioning

confidence: 99%

Androgens and male aging: current evidence of safety and efficacy

Gooren¹

2010

Asian J Androl

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Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

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Low Serum Testosterone and High Serum Estradiol Associate With Lower Extremity Peripheral Arterial Disease in Elderly Men

Cited by 108 publications

References 37 publications

Association between lipid profile and circulating concentrations of estrogens in young men

Association between lipid profile and circulating concentrations of estrogens in young men

Are declining testosterone levels a major risk factor for ill-health in aging men?

Androgens and male aging: current evidence of safety and efficacy

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