TY - JOUR
T1 - Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years
AU - Weller, Susan
AU - Davis, John W.
AU - Porterfield, Laura
AU - Chen, Lu
AU - Wilkinson, Gregg
N1 - Funding Information:
The authors gratefully acknowledge Joel Weissfeld, MD, MPH, at the Food and Drug Administration for sharing his protocol and hormone list. They also thank the Texas Academy of Family Physicians for funding. The data were obtained with a grant to SCW from the Texas Academy of the Family Physicians Foundation. The University of Texas Medical Branch Institutional Review Board approved the study without consent. This was a records-based study without direct patient or public involvement. All analyses were conducted with de-identified patient data and results reported in aggregate form, so that individuals could not be identified. All authors reviewed, edited, and approved the final draft. SCW designed and implemented the study, obtained funding for data and principal coder, drafted the manuscript, and is the guarantor of the study. JD contributed clinical expertise, participated in writing, and conducted statistical analyses. LP contributed clinical expertise, writing, and data interpretation. LC was the primary data coder, responsible for creating the dataset and variables. GSW participated in the design, implementation, interpretation, and editing of the manuscript. JWD is a consultant for GE healthcare. SCW received book sale royalties from Sage Co and is a lecturer in Summer Institute of Research Design of National Science Foundation. There are no competing interests to disclose. Not applicable.
Funding Information:
The authors gratefully acknowledge Joel Weissfeld, MD, MPH, at the Food and Drug Administration for sharing his protocol and hormone list. They also thank the Texas Academy of Family Physicians for funding.
Publisher Copyright:
© 2023 The Authors
PY - 2023/3
Y1 - 2023/3
N2 - 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: In a nested case-control study of US commercially insured women aged 50 to 64 years (2007-2019), cases were defined as incident VTE diagnoses and matched to 10 controls by date of VTE and age, excluding prior VTE, inferior vena cava filter placement, or anticoagulants. Filled prescriptions in the prior year defined hormone exposures. International Classification of Diseases and Current Procedural Terminology 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.
AB - 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: In a nested case-control study of US commercially insured women aged 50 to 64 years (2007-2019), cases were defined as incident VTE diagnoses and matched to 10 controls by date of VTE and age, excluding prior VTE, inferior vena cava filter placement, or anticoagulants. Filled prescriptions in the prior year defined hormone exposures. International Classification of Diseases and Current Procedural Terminology 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.
KW - contraceptives
KW - estrogens
KW - female
KW - menopause
KW - progesterone
KW - progestin
KW - venous thromboembolism
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U2 - 10.1016/j.rpth.2023.100135
DO - 10.1016/j.rpth.2023.100135
M3 - Article
AN - SCOPUS:85153242167
SN - 2475-0379
VL - 7
JO - Research and Practice in Thrombosis and Haemostasis
JF - Research and Practice in Thrombosis and Haemostasis
IS - 3
M1 - 100135
ER -