In older men higher plasma testosterone or dihydrotestosterone are independent predictors for reduced incidence of stroke but not myocardial infarction

Bu Yeap, Helman Alfonso, Paul Chubb, Graeme Hankey, D.J. Handelsman, J. Golledge, Osvaldo Almeida, Leon Flicker, Paul Norman

Research output: Contribution to journalArticle

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Abstract


Context:

Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial.


Objective:

We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men.


Participants and Methods:

Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70–89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage.


Results:

Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66–1.28; DHT: 0.83, 95% CI 0.59–1.15; E2: 0.84, 95% CI 0.62–1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39–0.81, P = .002; DHT: 0.57, 95% CI 0.40–0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54–1.08, P = .123).


Conclusions:

Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.
Original languageEnglish
Pages (from-to)4565-4573
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number12
DOIs
Publication statusPublished - 1 Dec 2014

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Dihydrotestosterone
Testosterone
Stroke
Myocardial Infarction
Plasmas
Incidence
Confidence Intervals
Hazards
Androgens
Independent Living
Information Storage and Retrieval
Liquid chromatography
Biomarkers
Metabolites
Liquid Chromatography
Mass spectrometry
Estradiol
Mass Spectrometry
Cardiovascular Diseases
Multivariate Analysis

Cite this

@article{59d6057c1b2549fcbd4baf1800bad143,
title = "In older men higher plasma testosterone or dihydrotestosterone are independent predictors for reduced incidence of stroke but not myocardial infarction",
abstract = "Context:Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial.Objective:We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men.Participants and Methods:Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70–89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage.Results:Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95{\%} confidence interval (CI) 0.66–1.28; DHT: 0.83, 95{\%} CI 0.59–1.15; E2: 0.84, 95{\%} CI 0.62–1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95{\%} CI 0.39–0.81, P = .002; DHT: 0.57, 95{\%} CI 0.40–0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95{\%} CI 0.54–1.08, P = .123).Conclusions:Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.",
author = "Bu Yeap and Helman Alfonso and Paul Chubb and Graeme Hankey and D.J. Handelsman and J. Golledge and Osvaldo Almeida and Leon Flicker and Paul Norman",
year = "2014",
month = "12",
day = "1",
doi = "10.1210/jc.2014-2664",
language = "English",
volume = "99",
pages = "4565--4573",
journal = "Journal of Endocrinology & Metabolism",
issn = "0021-972X",
publisher = "ENDOCRINE SOC",
number = "12",

}

TY - JOUR

T1 - In older men higher plasma testosterone or dihydrotestosterone are independent predictors for reduced incidence of stroke but not myocardial infarction

AU - Yeap, Bu

AU - Alfonso, Helman

AU - Chubb, Paul

AU - Hankey, Graeme

AU - Handelsman, D.J.

AU - Golledge, J.

AU - Almeida, Osvaldo

AU - Flicker, Leon

AU - Norman, Paul

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Context:Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial.Objective:We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men.Participants and Methods:Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70–89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage.Results:Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66–1.28; DHT: 0.83, 95% CI 0.59–1.15; E2: 0.84, 95% CI 0.62–1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39–0.81, P = .002; DHT: 0.57, 95% CI 0.40–0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54–1.08, P = .123).Conclusions:Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.

AB - Context:Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial.Objective:We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men.Participants and Methods:Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70–89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage.Results:Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66–1.28; DHT: 0.83, 95% CI 0.59–1.15; E2: 0.84, 95% CI 0.62–1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39–0.81, P = .002; DHT: 0.57, 95% CI 0.40–0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54–1.08, P = .123).Conclusions:Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.

U2 - 10.1210/jc.2014-2664

DO - 10.1210/jc.2014-2664

M3 - Article

VL - 99

SP - 4565

EP - 4573

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 12

ER -