Endogenous sex hormones and risk of venous thromboembolism in women and men

Haya N Holmegard; B G Nordestgaard; P Schnohr; A Tybjaerg-Hansen; M Benn

doi:10.1111/jth.12484

Endogenous sex hormones and risk of venous thromboembolism in women and men

Haya N Holmegard, B G Nordestgaard, P Schnohr, A Tybjaerg-Hansen, M Benn

Department of Clinical Medicine

33 Citations (Scopus)

Abstract

BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown.

OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population.

METHODS: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias.

RESULTS: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE.

CONCLUSION: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.

Original language	English
Journal	Journal of Thrombosis and Haemostasis
Volume	12
Issue number	3
Pages (from-to)	297-305
Number of pages	9
ISSN	1538-7933
DOIs	https://doi.org/10.1111/jth.12484
Publication status	Published - Mar 2014

Keywords

Adult
Aged
Aged, 80 and over
Contraceptives, Oral
Denmark
Estradiol
Female
Hormone Replacement Therapy
Humans
Male
Middle Aged
Prospective Studies
Pulmonary Embolism
Recurrence
Risk Factors
Testosterone
Time Factors
Venous Thromboembolism
Young Adult

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10.1111/jth.12484

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Cite this

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title = "Endogenous sex hormones and risk of venous thromboembolism in women and men",

abstract = "BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown.OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population.METHODS: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias.RESULTS: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE.CONCLUSION: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.",

keywords = "Adult, Aged, Aged, 80 and over, Contraceptives, Oral, Denmark, Estradiol, Female, Hormone Replacement Therapy, Humans, Male, Middle Aged, Prospective Studies, Pulmonary Embolism, Recurrence, Risk Factors, Testosterone, Time Factors, Venous Thromboembolism, Young Adult",

author = "Holmegard, {Haya N} and Nordestgaard, {B G} and P Schnohr and A Tybjaerg-Hansen and M Benn",

note = "{\textcopyright} 2013 International Society on Thrombosis and Haemostasis.",

year = "2014",

month = mar,

doi = "10.1111/jth.12484",

language = "English",

volume = "12",

pages = "297--305",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Endogenous sex hormones and risk of venous thromboembolism in women and men

AU - Holmegard, Haya N

AU - Nordestgaard, B G

AU - Schnohr, P

AU - Tybjaerg-Hansen, A

AU - Benn, M

PY - 2014/3

Y1 - 2014/3

N2 - BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown.OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population.METHODS: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias.RESULTS: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE.CONCLUSION: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.

AB - BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown.OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population.METHODS: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias.RESULTS: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE.CONCLUSION: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Contraceptives, Oral

KW - Denmark

KW - Estradiol

KW - Female

KW - Hormone Replacement Therapy

KW - Humans

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Pulmonary Embolism

KW - Recurrence

KW - Risk Factors

KW - Testosterone

KW - Time Factors

KW - Venous Thromboembolism

KW - Young Adult

U2 - 10.1111/jth.12484

DO - 10.1111/jth.12484

M3 - Journal article

C2 - 24329981

SN - 1538-7933

VL - 12

SP - 297

EP - 305

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

IS - 3

ER -

Endogenous sex hormones and risk of venous thromboembolism in women and men

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