Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses

Haya N Holmegard; Børge G Nordestgaard; Gorm B Jensen; Anne Tybjærg-Hansen; Marianne Benn

doi:10.1210/jc.2015-2687

Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses

Haya N Holmegard, Børge G Nordestgaard, Gorm B Jensen, Anne Tybjærg-Hansen, Marianne Benn

Department of Clinical Medicine

35 Citations (Scopus)

Abstract

Context and Objective: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear.Wetested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. Design, Setting, and Participants: Adultmen(n=4615) andwomen(n=4724) with measurements of endogenous sex hormones during the 1981â€"1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses. Main Outcome Measures: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists. Results: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations =10th percentile compared to the 11thâ€"90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05â€"1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09 â€"1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21â€"1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women. Conclusions: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.

Original language	English
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	101
Issue number	1
Pages (from-to)	69-78
Number of pages	10
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2015-2687
Publication status	Published - Jan 2016

Keywords

Adult
Age Factors
Aged
Body Mass Index
Brain Ischemia
Cohort Studies
Denmark
Estradiol
Female
Follow-Up Studies
Gonadal Steroid Hormones
Humans
Male
Middle Aged
Prospective Studies
Risk Assessment
Sex Factors
Stroke
Testosterone
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

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title = "Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses",

abstract = "Context and Objective: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear.Wetested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. Design, Setting, and Participants: Adultmen(n=4615) andwomen(n=4724) with measurements of endogenous sex hormones during the 1981{\^a}€{"}1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses. Main Outcome Measures: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists. Results: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations =10th percentile compared to the 11th{\^a}€{"}90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05{\^a}€{"}1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09 {\^a}€{"}1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21{\^a}€{"}1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women. Conclusions: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.",

keywords = "Adult, Age Factors, Aged, Body Mass Index, Brain Ischemia, Cohort Studies, Denmark, Estradiol, Female, Follow-Up Studies, Gonadal Steroid Hormones, Humans, Male, Middle Aged, Prospective Studies, Risk Assessment, Sex Factors, Stroke, Testosterone, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't",

author = "Holmegard, {Haya N} and Nordestgaard, {B{\o}rge G} and Jensen, {Gorm B} and Anne Tybj{\ae}rg-Hansen and Marianne Benn",

year = "2016",

month = jan,

doi = "10.1210/jc.2015-2687",

language = "English",

volume = "101",

pages = "69--78",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

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T1 - Sex Hormones and Ischemic Stroke

T2 - A Prospective Cohort Study and Meta-Analyses

AU - Holmegard, Haya N

AU - Nordestgaard, Børge G

AU - Jensen, Gorm B

AU - Tybjærg-Hansen, Anne

AU - Benn, Marianne

PY - 2016/1

Y1 - 2016/1

N2 - Context and Objective: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear.Wetested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. Design, Setting, and Participants: Adultmen(n=4615) andwomen(n=4724) with measurements of endogenous sex hormones during the 1981â€"1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses. Main Outcome Measures: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists. Results: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations =10th percentile compared to the 11thâ€"90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05â€"1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09 â€"1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21â€"1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women. Conclusions: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.

AB - Context and Objective: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear.Wetested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. Design, Setting, and Participants: Adultmen(n=4615) andwomen(n=4724) with measurements of endogenous sex hormones during the 1981â€"1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses. Main Outcome Measures: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists. Results: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations =10th percentile compared to the 11thâ€"90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05â€"1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09 â€"1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21â€"1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women. Conclusions: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.

KW - Adult

KW - Age Factors

KW - Aged

KW - Body Mass Index

KW - Brain Ischemia

KW - Cohort Studies

KW - Denmark

KW - Estradiol

KW - Female

KW - Follow-Up Studies

KW - Gonadal Steroid Hormones

KW - Humans

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Risk Assessment

KW - Sex Factors

KW - Stroke

KW - Testosterone

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, Non-U.S. Gov't

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DO - 10.1210/jc.2015-2687

M3 - Journal article

C2 - 26509870

SN - 0021-972X

VL - 101

SP - 69

EP - 78

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 1

ER -

Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses

Abstract

Keywords

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