In Older Men an Optimal Plasma Testosterone Is Associated With Reduced All-Cause Mortality and Higher Dihydrotestosterone With Reduced Ischemic Heart Disease Mortality, While Estradiol Levels Do Not Predict Mortality

Yeap, Bu B.; Alfonso, Helman; Chubb, S. A. Paul; Handelsman, David J.; Hankey, Graeme J.; Almeida, Osvaldo P.; Golledge, Jonathan; Norman, Paul; Flicker, Leon

doi:10.1210/jc.2013-3272

Cited by 159 publications

(140 citation statements)

References 44 publications

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“…This may reflect tissue actions of DHT, with experimental studies demonstrating attenuation of development of atherosclerosis with DHT exposure [38]. We have previously reported that higher DHT is associated with reduced mortality from ischaemic heart disease in older men [39], thus our current findings in younger men may be important for the consideration of future interventional studies. Of note, our results reinforce the importance of T, DHT and E2 rather than SHBG or LH, for risk stratification, particularly when LC-MS is available for the assay of these sex steroids.…”

Section: Discussionmentioning

confidence: 58%

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

et al. 2015

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CIRCULATING TESTOSTERONE (T) is lower in older men compared with younger men, and older men have a higher incidence and prevalence of cardiovascular disease (CVD) [1,2]. In epidemiological studies, lower T concentrations are also associated with a range of adverse health outcomes, including increased risk of CVD and all-cause mortality [3,4]. On the contrary, benefits of T supplementation have not been recipro- Abstract. Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality. Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B). Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically. In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT. In men with CAD, higher DHT or E2 are associated with less carotid plaque. T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.

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Section: Discussionmentioning

confidence: 58%

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

et al. 2015

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“…The similarity of this index of androgen status with the temporal profile of testosterone and of DHT is consistent with the relative stability of the DHT/testosterone ratio (median 0.10) across a large population of men. Nevertheless, although DHT is usually converted from testosterone by 5a reductase, the independent backdoor pathway that synthesizes DHT bypassing testosterone (54) allows for independent regulation of serum DHT levels with potentially differential effects on health outcomes such as cardiovascular disease and mortality (55,56). Hence, this novel response metameter, incorporating simultaneous measurements of both testosterone and DHT, may provide a more comprehensive metric to characterize androgen status for individual men and male populations where the impact on the two major androgens may diverge.…”

Section: Discussionmentioning

confidence: 99%

Age-specific population centiles for androgen status in men

Handelsman

Yeap

Flicker

et al. 2015

European Journal of Endocrinology

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Aim: The age-specific population profiles in men of circulating testosterone and its two bioactive metabolites dihydrotestosterone (DHT) and estradiol (E 2 ) across the adult lifespan and its determinants are not well described. Objective: Our objective was to deduce smoothed age-specific centiles of circulating testosterone, DHT, and E 2 in men using pooled data from population-based studies in three Australian cities from liquid chromatography-mass spectrometry steroid measurements in a single laboratory. Design, setting, and participants: We pooled data of 10 904 serum samples (serum testosterone, DHT, E 2 , age, height, and weight) from observational population-based studies in three major cities across Australia. Main outcome measures: Age-specific smoothed centiles for serum testosterone, DHT, and E 2 in men aged 35-100 years were deduced by large sample data analysis methods. Results: We found that serum testosterone, DHT, and E 2 decline gradually from ages 35 onwards with a more marked decline after 80 years of age. Higher weight, BMI, and body surface area as well as shorter stature are associated with reduced serum testosterone, DHT, and E 2 . Conclusions: Among Australian men, there is a gradual progressive population-wide decline in androgen status during male aging until the age of 80 years after which there is a more marked decline. Obesity and short stature are associated with reduced androgen status. Research into the age-related decline in androgen status should focus on the progressive accumulation of age-related comorbidities to better inform optimal clinical trial design.

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“…These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men. Optimal androgen levels seem to be a biomarker for survival because men with mid-range levels of testosterone and dihydro-testosterone were recently reported to have the lowest death rate from any cause (18). This was obvious also in the present study, where intermediate testosterone concentrations (9.26-14.90 nmol/l) considered as 'lownormal' were protective against CVD death in the followup of the patients, and the men with suppressed testosterone in the acute phase had increased risk of subsequent ACS in the follow-up of 6 years.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Adaptation to acute coronary syndrome-induced stress with lowering of testosterone: a possible survival factor

Pesonen

Pussinen

Huhtaniemi

2016

European Journal of Endocrinology

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Objective: The objective of this study was to explore whether circulating testosterone (T) concentration is associated with the occurrence and risk for acute coronary syndromes (ACS). Method: This case-control study included male patients with acute myocardial infarction (AMI) (nZ174) or unstable angina pectoris (UAP) (nZ90) and healthy controls (nZ238). Patients gave serum samples during the acute (nZ264) and recovery (nZ132) phases after a median of 10.5 months after the incident event. Secondary events (ACS or cardiovascular death) were registered during the following 6 years. Results: During the acute phase, AMI and UAP patients had similar significantly reduced concentrations of serum testosterone in comparison to controls. Testosterone associated inversely with weight, the degree of inflammation (i.e. C-reactive protein concentration) and signs of a chronic infection. In a multiadjusted Cox regression, when compared to testosterone concentrations considered high-normal (14.91-34.0 nmol/l), low-normal testosterone (9.26-14.90 nmol/l) in the acute phase predicted better prognosis for cardiovascular death rate with a hazard ratio (HR) of 0.17 (0.04-0.68, PZ0.012). The increased testosterone concentrations after the recovery period did not associate with future cardiovascular disease events. Conclusion: Low-normal testosterone levels in the acute phase of ACS predicted better survival. The observation may indicate better adaptation to stress in survivors and warrants further study.

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In Older Men an Optimal Plasma Testosterone Is Associated With Reduced All-Cause Mortality and Higher Dihydrotestosterone With Reduced Ischemic Heart Disease Mortality, While Estradiol Levels Do Not Predict Mortality

Cited by 159 publications

References 44 publications

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

Age-specific population centiles for androgen status in men

Adaptation to acute coronary syndrome-induced stress with lowering of testosterone: a possible survival factor

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