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Clinical Endocrinology

Lower plasma testosterone or dihydrotestosterone, but not estradiol, is associated with symptoms of intermittent claudication in older men

Authors

  • Bu B. Yeap,

    Corresponding author
    1. Department of Endocrinology and Diabetes, Fremantle Hospital, Fremantle, WA, Australia
    • School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
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  • Helman Alfonso,

    1. Western Australian Centre for Health and Ageing, Centre for Medical Research, University of Western Australia, Perth, WA, Australia
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  • S. A. Paul Chubb,

    1. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
    2. PathWest Laboratory Medicine, Fremantle and Royal Perth Hospitals, Perth, WA, Australia
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  • David J. Handelsman,

    1. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
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  • Graeme J. Hankey,

    1. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
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  • Jonathan Golledge,

    1. Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville, Qld, Australia
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  • Leon Flicker,

    1. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
    2. Western Australian Centre for Health and Ageing, Centre for Medical Research, University of Western Australia, Perth, WA, Australia
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  • Paul E. Norman

    1. School of Surgery, University of Western Australia, Perth, WA, Australia
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Correspondence: Bu B. Yeap, School of Medicine and Pharmacology, Fremantle Hospital, Level 2, T Block, Alma Street, Fremantle, WA 6160, Australia. Tel.: +61 (8) 9431 3229; Fax: +61 (8) 9431 2977; E-mail: byeap@cyllene.uwa.edu.au

Summary

Objective

In men, testosterone (T) levels decline with age, and lower T predicts all-cause and cardiovascular mortality. However, the associations of T and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with symptomatic peripheral arterial disease remain unclear. We assessed associations of T, DHT and E2 with lower limb intermittent claudication in older men.

Design

Cross-sectional study.

Participants

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

Measurements

Intermittent claudication was ascertained by the Edinburgh Claudication Questionnaire. Early morning, plasma T, DHT and E2 were assayed using liquid chromatography–tandem mass spectrometry.

Results

There were 268 men with intermittent claudication and 2435 without claudication or any leg pain. Men with nonspecific leg pain (n = 986) were excluded. After adjusting for age, smoking, BMI, waist/hip ratio, hypertension, dyslipidaemia, diabetes, creatinine and prevalent cardiovascular disease (CVD), higher T was associated with reduced risk of having claudication (per 1 SD increase, odds ratio [OR] = 0·80, 95% confidence interval [CI] = 0·69–0·94, P = 0·006; quartiles, Q4/Q1, OR = 0·54, 95% CI = 0·36–0·81). Higher DHT was associated with reduced risk of having claudication (per 1 SD increase, OR = 0·86, 95% CI = 0·73–1·00, P = 0·048; Q4/Q1, OR = 0·64, 95% CI = 0·43–0·95). E2 was not associated with claudication (per 1 SD increase, OR = 0·96, 95% CI = 0·83–1·11, P = 0·565; Q4/Q1, OR = 0·88, 95% CI = 0·60–1·29).

Conclusions

Lower T or DHT levels, but not E2, are associated with symptoms of intermittent claudication in older men. Reduced exposure to androgens may represent a causal factor or biomarker for symptomatic peripheral arterial disease. Further studies are needed to examine underlying mechanisms and evaluate therapeutic options in ageing men.

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