Reference ranges and determinants of testosterone, dihydrotestosterone and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. — ASN Events
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Reference ranges and determinants of testosterone, dihydrotestosterone and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. (#157)

Bu B Yeap 1 2 , Helman Alfonso 3 , Paul Chubb 4 , David J Handelsman 5 , Graeme J Hankey 1 , Paul E Norman 6 , Leon Flicker 1 3
  1. School of Medicine, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Fremantle Hospital, Fremantle, WA, Australia
  3. School of Medicine, University of Western Australia, Perth, WA, Australia
  4. PathWest Laboratory Medicine, Fremantle and Royal Perth Hospitals, Perth, WA, Australia
  5. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
  6. School of Surgery, University of Western Australia, Perth, WA, Australia

Context
In men, testosterone (T) levels decline with increasing age, while the prevalence of ill-health increases. Controversy exists over the appropriate threshold for classifying T as low rather than normal in older men. The relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) to define hormonal status in this context remains unclear.

Objective
We assessed distributions and associations of T, DHT and E2 in men aged ≥70 years, and established reference ranges for these in healthy older men.

Participants
Community-dwelling men aged 70-89 years resident in Perth, Western Australia.

Main outcome measures
Demographic, medical and physical characteristics of the cohort were collated. Plasma T, DHT and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples from 3,690 men.

Results
In the cohort as a whole, mean±SD for T was 13.1±4.9 nmol/L, DHT 1.4±0.7 nmol/L and E2 73.4±29.1 pmol/L. Increasing age, higher body mass index, waist:hip ratio, dyslipidemia, diabetes and higher luteinising hormone (LH) were independently associated with T and DHT in the lowest quartile. Increasing age, diabetes and higher LH were associated with lower E2. In a reference group of 394 men aged 74.2±3.8 years reporting excellent or very good health with no history of smoking, diabetes, cardiovascular disease (CVD), cancer, depression or dementia, the 2.5th percentile for T was 6.4 nmol/L, DHT 0.49 nmol/L and E2 28 pmol/L. Applying these cut-offs to all 3,690 men, those with low T or low DHT had increased odds ratio (OR) for frailty, diabetes and CVD. Men with both low T and low DHT had higher OR for these outcomes.

Conclusions
The 2.5th percentile in a reference group of healthy older men provides age-appropriate thresholds for defining low T, DHT and E2. Additional studies are needed to test their potential applicability and clinical utility in older men.