Open AccessBiomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative
Author(s) -
Cushman Mary,
Larson Joseph C.,
Rosendaal Frits R.,
Heckbert Susan R.,
Curb J. David,
Phillips Lawrence S.,
Baird Alison E.,
Eaton Charles B.,
Stafford Randall S.
Publication year - 2018
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12100
Subject(s) - medicine , thrombosis , venous thrombosis , hormone therapy , placebo , odds ratio , estrogen , hormone replacement therapy (female to male) , medroxyprogesterone acetate , breast cancer , cancer , pathology , testosterone (patch) , alternative medicine
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.