Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years
Susan C. Weller, John W. Davis, Laura Porterfield, Lu Chen, Gregg S. Wilkinson
Abstract
Background: Menopausal hormone therapy (MHT) can elevate venous thromboembolism (VTE) risk, but less is known about formulations and routes of exposures. Objective: To estimate hormone-associated VTE risk by route and formulation in exposed and unexposed women aged 50 to 64 years in the US. Methods: codes identified risk factors and comorbidities. Results: Odds ratios (ORs) were estimated with conditional logistic regression controlling for differences between cases (n = 20,359) and controls (n = 203,590) in comorbidities and VTE risk factors. For exposures within 60 days, oral MHT risk was almost twice as high as transdermal MHT (OR = 1.92; 95% CI, 1.43-2.60); transdermal MHT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96). Risk was highest for MHT combinations with ethinyl estradiol, followed by conjugated equine estrogen (CEE) (ethinyl estradiol-CEE: OR = 1.55; 95% CI, 1.07-2.25), and lowest for estradiol (CEE-estradiol: OR = 1.33; 95% CI, 1.02-1.72). Combined hormonal contraceptives elevated risk 5 times higher than no exposure (OR = 5.22; 95% CI, 4.67-5.84) and 3 times higher than oral MHT (OR = 3.65; 95% CI, 3.09-4.31). Conclusion: The risk of VTE is much lower with MHT than combined hormone contraceptives and varies by hormone formulation and route of exposure. Transdermal MHT did not elevate risk. Oral MHT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal MHT.