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Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.

ABSTRACT: Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men.Cohort study.Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010.Adjudicated ischaemic stroke.Among 1032 men (mean age 76, range 66-97), followed for a median of 10 years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P = 0·006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75 ng/dl, with greater risk of stroke at DHT levels above 75 ng/dl or below 50 ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0·77 (95% CI, 0·61, 0·98) per standard deviation in analyses adjusted for stroke risk factors.Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.

SUBMITTER: Shores MM

PROVIDER: S-EPMC4169352 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.

Shores Molly M MM Arnold Alice M AM Biggs Mary L ML Longstreth W T WT Smith Nicholas L NL Kizer Jorge R JR Cappola Anne R AR Hirsch Calvin H CH Marck Brett T BT Matsumoto Alvin M AM

Clinical endocrinology 20140505 5

<h4>Objective</h4>Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men.<h4>Design</h4>Cohort study.<h4>Participants</h4>Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010.<h4>Measurements</h4>Adjudicated ischaemic strok ...[more]

PMID: 24645738

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Project description:Erythrocytosis is the most common dose limiting adverse effect of testosterone therapy but the mechanisms of testosterone mediated erythropoiesis remain unclear. In this study we examine risk factors for erythrocytosis associated with testosterone therapy.A retrospective review was performed of 179 hypogonadal men on testosterone therapy at a single andrology clinic. Demographic data, testosterone therapy formulation and duration of treatment, and 5?-reductase inhibitor use were assessed. Serum dihydrotestosterone, total testosterone, free testosterone, follicle-stimulating hormone, luteinizing hormone, hematocrit and lipid levels were extracted, and changes during treatment were determined. Spearman's rank correlation was used to identify relationships between change in hematocrit and study variables.Of 179 patients 49 (27%) experienced a 10% or greater change in hematocrit and erythrocytosis (hematocrit 50% or greater) developed in 36 (20.1%) at a median followup of 7 months. Topical gels were used by 41.3% of patients, injectable testosterone by 52.5% and subcutaneous pellets by 6.1%. More men who experienced a change in hematocrit of 10% or greater used injectable testosterone than men with a change in hematocrit of less than 10% (65% vs 48%, p=0.035), and were less likely to be on a 5?-reductase inhibitor (2% vs 15%, p=0.017). Men with a change in hematocrit of 10% or greater had higher posttreatment dihydrotestosterone levels (605.0 vs 436.0 ng/dl, p=0.017) and lower luteinizing hormone and follicle-stimulating hormone levels than men with a change in hematocrit of less than 10%. Spearman's rank correlations yielded relationships between change in hematocrit and posttreatment dihydrotestosterone ?=0.258, p=0.001) and total testosterone (?=0.171, p=0.023).Dihydrotestosterone may have a role in testosterone therapy related erythrocytosis and monitoring dihydrotestosterone levels during testosterone therapy should be considered. In men in whom erythrocytosis develops, 5?-reductase inhibitors may be therapeutic.

Dataset Information

Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.

Publications

Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.

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