Abstract

Essentials

Venous thrombosis is the most common vascular complication of menopausal hormone use.We studied biomarkers to predict thrombosis with hormones in the Women's Health Initiative.Lower proteins C and S, and higher D‐dimer were related to thrombosis risk.The 25% of women with high D‐dimer had a six‐times greater risk of thrombosis with hormones.

Background

Oral menopausal hormone therapy causes venous thrombosis but whether biomarkers of thrombosis risk can identify women at risk is unknown.

Methods

We completed a nested case control study in the two Women's Health Initiative hormone trials; 27 347 women aged 50‐79 were randomized to hormone therapy (conjugated equine estrogen with or without medroxyprogesterone acetate) or placebo. With 4 years follow‐up, biomarkers were measured using stored baseline samples prior to starting treatment, and one‐year later, in 215 women who developed thrombosis and 867 controls.

Results

Overall, lower protein C and free protein S, and higher D‐dimer, prothrombin fragment 1.2 and plasmin‐antiplasmin complex were associated with risk of future thrombosis with odds ratios ranging from 1.9 to 3.2. Compared to women with normal biomarkers assigned to placebo, the risk of thrombosis with hormone therapy was increased among women with abnormal biomarkers, especially elevated D‐dimer, elevated plasmin‐antiplasmin, and low free protein S; the largest association was for D‐dimer: odds ratio 6.0 (95% CI 3.6‐9.8). Differences in associations by hormone use were not significant on the multiplicative scale. Considering a multi‐marker score of eight biomarkers, women with three or more abnormal biomarkers had 15.5‐fold increased odds of VT (95% CI 6.8‐35.1). One‐year changes in biomarkers were not robustly associated with subsequent thrombosis risk.

Conclusion

Abnormal levels of biomarkers of thrombosis risk identified women at increased risk of future venous thrombosis with oral menopausal hormone therapy. Findings support the potential for clinical use of D‐dimer testing in advance of hormone therapy prescription.

Details

Title
Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative
Author
Cushman, Mary 1   VIAFID ORCID Logo  ; Larson, Joseph C 2 ; Rosendaal, Frits R 3   VIAFID ORCID Logo  ; Heckbert, Susan R 4 ; Curb, J David 5 ; Phillips, Lawrence S 6 ; Baird, Alison E 7 ; Eaton, Charles B 8 ; Stafford, Randall S 9 

1  Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA 
2  Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 
3  Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands 
4  Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA 
5  Department of Geriatric Medicine, University of Hawaii, Honolulu, HI, USA 
6  Atlanta VA Medical Center, Decatur, GA, USA; Division of Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, GA, USA 
7  Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY, USA 
8  Department of Family Medicine, Alpert Medical School, Brown University, Providence, RI, USA; Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA 
9  Program on Prevention Outcomes and Practices, Stanford Prevention Research Center, Stanford University, Palo Alto, CA, USA 
Pages
310-319
Section
ORIGINAL ARTICLES: THROMBOSIS
Publication year
2018
Publication date
Apr 2018
Publisher
Elsevier Limited
e-ISSN
24750379
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/rth2.12100
ProQuest document ID
2331417954
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.