Endogenous sex hormones and risk of venous thromboembolism in young women
the CREW consortium
(2019) Journal of Thrombosis and Haemostasis, volume 17, issue 8, pp. 1297 - 1304
(Article)
Abstract
Background: The risk of venous thromboembolism (VTE) in young women can predominantly be attributed to exogenous hormone use. The influence of (abnormalities in) endogenous sex hormones, as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI), on VTE risk is uncertain. Objectives: Th assess the association between endogenous sex
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hormone levels and VTE risk. Methods: Women aged ≤45 years from the MEGA case-control study who provided a blood sample in the absence of exogenous hormone exposure or pregnancy were included. Sex hormone–binding globulin (SHBG), estradiol, follicle-stimulating hormone (FSH) and testosterone were measured. The free androgen index (FAI) and estradiol to testosterone ratio (E:T) were calculated. VTE risk was assessed according to quartiles (Qs) of levels and clinical cut-offs as proxies for PCOS (FAI > 4.5) and POI (FSH > 40 U/L). Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: Six hundred and sixty-five women (369 cases; 296 controls) were eligible for the analyses. Testosterone and FSH levels, E:T and POI (FSH > 40 U/L vs FSH ≤ 40 U/L) were not associated with VTE risk. For estradiol, VTE risk was increased with levels in Q4 vs Q1 (OR 1.6; 95% CI 1.0-2.5). There was a dose-response relationship between SHBG levels and VTE risk, with the highest OR at Q4 vs Q1: 2.0 (95% CI 1.2-3.3). FAI > 4.5 (PCOS proxy) vs FAI ≤ 4.5 was associated with increased VTE risk (OR 3.3; 95% CI 0.9-11.8). Conclusions: Estradiol, SHBG and FAI were associated with VTE risk, suggesting a role for endogenous sex hormones in the pathophysiology of VTE in young women.
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Keywords: Adult, Age Factors, Biomarkers/blood, Case-Control Studies, Estradiol/blood, Female, Gonadal Steroid Hormones/blood, Humans, Middle Aged, Netherlands, Polycystic Ovary Syndrome/blood, Primary Ovarian Insufficiency/blood, Risk Assessment, Risk Factors, Sex Factors, Sex Hormone-Binding Globulin/analysis, Testosterone/blood, Venous Thromboembolism/blood, hormones, premature ovarian failure, polycystic ovary syndrome, venous thromboembolism, women, Research Support, Non-U.S. Gov't, Multicenter Study, Journal Article
ISSN: 1538-7933
Publisher: Wiley-Blackwell
Note: Funding Information: L. J. J. Scheres is a PhD candidate of the CREW project (2013T083) supported by the Netherlands Heart Foundation. This study was funded in part by a VIDI innovative research grant of the Netherlands Organization for Health Research and Development (ZonMw, 016.126.364) of S. Middeldorp. Publisher Copyright: © 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis
(Peer reviewed)