Performance of Direct Estradiol Immunoassays with Human Male Serum Samples

Handelsman, David J.; Newman, Julie; Jimenez, Mark; McLachlan, Robert I; Sartorius, Gideon; Jones, Graham

doi:10.1373/clinchem.2013.213363

Cited by 72 publications

(47 citation statements)

References 39 publications

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“…Other previous studies have reported stable serum E 2 levels with regard to male aging using conventional RIAs (38,39,40,46) or GC-MS (43,47,48), whereas studies using direct immunoassays reported no change (49, 50) or a decline (51). Some of these discrepancies are likely due to the unreliability of E 2 immunoassays at the low circulating levels prevailing in men (24,25,26,52 The mechanism and significance of the biochemical decline in androgen status affecting aging men cannot be determined from the present observational study. Nevertheless, an important and plausible explanation is that this decline reflects the impact of the co-morbidities accumulating during aging on an otherwise healthy reproductive system.…”

Section: Discussioncontrasting

confidence: 63%

“…Furthermore, serum DHT was rarely measured in population-based studies as few in-house DHT immunoassays were available and none in multiplex or valid single-tube formats (23). Similarly, serum E 2 was usually measured by direct immunoassays, which are inaccurate at the low circulating E 2 levels prevailing in men of all ages (24,25,26). Finally, few studies reported measuring serum testosterone, DHT, and E 2 in studies of thousands of participants (21,22).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 63%

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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“…These findings are supported by an observational study showing elevated risk of stroke with high levels of E2 [36]. Previous studies have mostly relied on E2 measured using immunoassay [11,15,18,19], which has been shown to be unreliable for measurement of E2 in men [22]. Furthermore, studies assessing the association between E2 and carotid plaque in men with CAD are lacking.…”

Section: Discussionmentioning

confidence: 86%

“…These studies of T and E2 consist of heterogeneous populations of men with coronary artery disease (CAD), and are limited by the use of radioimmunoassay for assay of T and E2. More accurate assay of T, and of DHT and E2 can be undertaken using mass spectrometry [21,22]. Studies examining the association of DHT with preclinical carotid atherosclerosis are lacking.…”

Section: Assessment Of Cimt and Carotid Plaquementioning

confidence: 99%

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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“…Second, sex steroid hormones are known to vary on a diurnal basis, and the use of a single measurement for each of these biomarkers could potentially lead to non-differential misclassification bias. In addition, sex steroid hormones were measured by immunoassays and vitamin D was measured using DiaSorin(rather than mass spectrometry) which are now widely understood to be suboptimal for clinical research involving women, children or men with low serum testosterone [44,45] and especially for serum estradiol in men [46,47]. However, previous studies have indicated an association between testosterone levels and adverse events, irrespective of whether immunoassays or mass-spectrometry measurements were applied [5,14,15].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and biomarkers of sex steroid hormones are non-linearly and inversely related to all-cause mortality: results from NHANES III

Beydoun¹,

Eid²,

Jeng³

et al. 2015

Horm Stud

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Background: In men, hypovitaminosis D as well as high and low testosterone levels have been linked to adverse events, including death. A biological interaction has been previously suggested between vitamin D and androgens. In a cohort study using Third National Health and Nutrition Examination Survey data, we simultaneously investigated circulating vitamin D and biomarkers of sex steroid hormones as predictors of all-cause mortality. Methods: Age-adjusted and fully-adjusted Cox regression models were constructed to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Whereas the vitamin D sufficient group (25(OH)D 3 ≥30 ng/ml) was selected as a referent, biomarkers of sex steroid hormones (testosterone, estradiol, SHBG) were defined as Loge-transformed continuous variables. Results: Of 1,472 men with a mean age of 42.1 years at baseline, 382 died over a median of 192 months of follow-up. Estradiol levels were significantly higher among vitamin D deficient compared to vitamin D sufficient men and sex hormone binding globulin level was significantly higher in vitamin D sufficient compared to vitamin D insufficient or deficient groups. An inverse non-linear relationship was observed between all-cause mortality rate and levels of testosterone, estradiol and vitamin D, in fully-adjusted models. There were no significant interaction effects between vitamin D and sex steroid hormones in relation to all-cause mortality rate. Conclusions: Vitamin D and sex steroid hormones, but not sex hormone binding globulin, may be inversely and non-linearly related to all-cause mortality among adult men, after adjustment for baseline demographic, socioeconomic, lifestyle and clinical characteristics.

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Performance of Direct Estradiol Immunoassays with Human Male Serum Samples

Cited by 72 publications

References 39 publications

Age-specific population centiles for androgen status in men

Age-specific population centiles for androgen status in men

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

Vitamin D and biomarkers of sex steroid hormones are non-linearly and inversely related to all-cause mortality: results from NHANES III

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