Exogenous estrogens, a heterogeneous group of estrogenic compounds that includes conjugated equine estrogen (CEE), estradiol (E2), and esterified estrogen (EE), are a controversial and potentially harmful pharmaceutical therapy that nonetheless continues to be used by peri- and post-menopausal women. Venous thrombosis (VT) may be one of the most serious side-effect of short-term estrogen use. It has been demonstrated that CEE, historically the most commonly prescribed estrogen, and EE, have differential effects on VT risk. Estradiol is the second most commonly prescribed oral estrogen in the US and its association with VT risk is not known. This application is a competing renewal to support novel work investigating estrogens and pharmacogenetic risk factors for VT in peri- and post-menopausal women in a population-based, case-control study at Group Health. The recent change in the preferred formulary estrogen at Group Health to E2 provides us with a unique opportunity to characterize the VT risk associated with this commonly used oral estrogen. As our primary aim in this renewal, we hypothesize that VT risk is greater in users of oral E2 compared with non-users of estrogen and, moreover, VT risk is greater in oral E2 users compared with oral CEE users or compared with oral EE users. As a secondary aim, we will use laboratory-based measures to characterize the clotting propensity of oral E2, oral CEE, and non-users of estrogen among healthy subjects. An additional aim is to determine which newly identified genetic risks of thrombosis from the growing literature are modified by estrogen use. The setting for the study is Group Health, a large integrated healthcare organization in Washington State. The study population will include peri- and post-menopausal Group Health members 30 to 89 years of age who experienced an incident VT, either deep vein thrombosis or fatal or non-fatal pulmonary embolism. This application will support the identification and the abstraction of medical record data VT cases and their matched controls that occur through 2013. Blood will be collected and DNA abstracted from those who consent. Data on the safety of oral estrogen products are limited and hinder women and their physicians from making evidence-based decisions when choosing an estrogen product to treat vasomotor symptoms of menopause. This competing renewal is designed to expand research using this unique and valuable resource that has already produced important epidemiologic information and will likely provide high-quality data to begin to address important public health questions of women's health.
Data on the safety of oral estrogen products are limited and hinder women and their physicians from making evidence-based decisions when choosing an estrogen product to treat vasomotor symptoms of menopause. Venous thrombosis may be the most serious side-effect of short-term estrogen use yet virtually nothing is known about the risks of oral estradiol, the second most commonly used estrogen. We propose an extension of our population-based, case-control study in post-menopausal women to examine risks of venous thrombosis associated with oral estradiol and other estrogens.
|Cheng, Yu-Ching; Stanne, Tara M; Giese, Anne-Katrin et al. (2016) Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2. Stroke 47:307-16|
|Harrington, Laura B; Wiggins, Kerri L; Sitlani, Colleen M et al. (2016) The association of F11 genetic variants with the risk of incident venous thrombosis among women, by statin use. Thromb Haemost 115:682-4|
|Harrington, Laura B; Marck, Brett T; Wiggins, Kerri L et al. (2016) Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women. J Thromb Haemost :|
|Harrington, Laura B; Weiss, Noel S; Wiggins, Kerri L et al. (2016) Prior hysterectomy and oophorectomy and incident venous thrombosis risk among postmenopausal women: a population-based, case-control study. Menopause 23:143-9|
|Smith, N L; Harrington, L B; Blondon, M et al. (2016) The association of statin therapy with the risk of recurrent venous thrombosis. J Thromb Haemost 14:1384-92|
|Floyd, James S; Wiggins, Kerri L; Christiansen, Mark et al. (2016) Case-control study of oral glucose-lowering drugs in combination with long-acting insulin and the risks of incident myocardial infarction and incident stroke. Pharmacoepidemiol Drug Saf 25:151-60|
|Floyd, J S; Wiggins, K L; Sitlani, C M et al. (2015) Case-control study of second-line therapies for type 2 diabetes in combination with metformin and the comparative risks of myocardial infarction and stroke. Diabetes Obes Metab 17:1194-7|
|Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S et al. (2015) Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. Neurology 84:2132-45|
|Germain, Marine; Chasman, Daniel I; de Haan, Hugoline et al. (2015) Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. Am J Hum Genet 96:532-42|
|Bis, Joshua C; Sitlani, Colleen; Irvin, Ryan et al. (2015) Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium. PLoS One 10:e0140496|
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