Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self‐reporting very good health: the healthy man study

Sartorius, Gideon; Spasevska, Sasa; Idan, Amanda; Turner, Leo; Forbes, Elise A; Zamojska, Anna; Allan, Carolyn; Ly, Linda; Conway, Ann J.; McLachlan, Robert I; Handelsman, David J.

doi:10.1111/j.1365-2265.2012.04432.x

Cited by 190 publications

(122 citation statements)

References 41 publications

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“…Similarly, our finding of minimal changes in serum E 2 is consistent with a comparable trend in serum E 2 with age in the community-based Framingham Offspring Study (44) and our Healthy Man Study (45). 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).…”

Section: Discussionsupporting

confidence: 77%

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: Discussionsupporting

confidence: 77%

Age-specific population centiles for androgen status in men

Handelsman

Yeap

Flicker

et al. 2015

European Journal of Endocrinology

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“…Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the age-related decline in testosterone levels (Travison et al 2007, Haring et al 2010. Indeed, there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in testosterone (Sartorius et al 2012). Circulating testosterone, on an average 30%, is lower in obese compared with lean men, which is more than the purely age-dependent decrease between 40 and 80 years of age ).…”

Section: Evidence That Low Testosterone Is a Consequence Of Dysglycaementioning

confidence: 99%

“…Several lines of evidence (Farooqi et al 2002, Zumoff et al 2003, Travison et al 2008, Grossmann 2011, Sartorius et al 2012, Camacho et al 2013, Corona et al 2013a,b, George et al 2013, summarised in Box 1, suggest that the in the majority of men, suppression of the diabesity-associated HPT axis is functional, and may hence be reversible. Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al 2012b) are important contributors to the suppression of the HPT axis.…”

Section: Testosterone and Insulin Resistance: A Bilateral Relationshipmentioning

confidence: 99%

Testosterone and glucose metabolism in men: current concepts and controversies

Grossmann¹

2013

Journal of Endocrinology

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A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic-pituitary-testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

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“…To validate the serum E 2 measurements in the LC-MS assay, 3 certified reference materials (CRMs) for serum E 2 (CRM 576, CRM 577, and CRM 578) obtained from the European Commission's Institute for Reference Materials and Measurements (23 ) were run in duplicate on consecutive days in the LC-MS assay, including 1 set run together with the samples in this study. Serum T was measured in the same sample by the same LC-MS method (22 ) and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) by immunoassays as reported previously (21 ).…”

Section: Assaysmentioning

confidence: 99%

“…A reference panel of sera was formed from a nested cohort of participants in the Healthy Man Study (21 ) who were Ͼ40 years old and reported excellent or very good health with no health symptoms including sexual dysfunction or gynecomastia. Previously unthawed aliquots of serum (n ϭ 101) collected during the study were distributed frozen to 5 laboratories, all holding accreditation to International Organization for Standardization (ISO) 15189 and participating in the national RCPAQAP (Royal College of Pathologists of Australasia Quality Assurance Programs) quality assurance program.…”

Section: Samplesmentioning

confidence: 99%

Performance of Direct Estradiol Immunoassays with Human Male Serum Samples

Handelsman

Newman²,

Jimenez

et al. 2014

Clinical Chemistry

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BACKGROUND:Steroid immunoassays originally required solvent extraction, chromatography, and structurally authentic tracers to avoid interference from steroid cross-reactivity and matrix effects. The demand for steroid assays has driven assay simplification, bypassing this triplet of validity criteria to allow use of unextracted serum, which has introduced bias and nonspecificity at low steroid concentrations. We aimed to evaluate the performance of commercial direct estradiol (E 2 ) immunoassays relative to the reference method of LC-MS and compared serum E 2 measurements from each assay with biomarkers of estrogen action.

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Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self‐reporting very good health: the healthy man study

Cited by 190 publications

References 41 publications

Age-specific population centiles for androgen status in men

Age-specific population centiles for androgen status in men

Testosterone and glucose metabolism in men: current concepts and controversies

Performance of Direct Estradiol Immunoassays with Human Male Serum Samples

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