A nationwide Danish cohort study of nearly 1.4 million women found significant variations in venous thromboembolism risk across different types of hormonal contraceptives, with combined hormonal contraceptives showing the highest risk and intrauterine devices demonstrating no increased risk compared with nonuse.
The research, published in JAMA, analyzed data from 1,397,235 women aged 15 to 49 over 8.5 million person-years, during which 2691 venous thromboembolism (VTE) events occurred.
The study found that compared with nonuse of hormonal contraception, the adjusted rate ratios for VTE were 4.6 for combined pills, 4.5 for vaginal rings, 5.0 for patches, 1.8 for progestin-only pills, and 1.0 for intrauterine devices (IUDs).
"Variation in VTE risk across products underscores the importance of personalized contraceptive counseling," the study authors emphasized.
The standardized VTE rates per 10,000 person-years varied considerably: 2.0 for nonuse, 10.0 for combined pills, 8.0 for vaginal rings, and 8.1 for patches.
Among combined pills, the excess VTE risk per 10,000 person-years ranged from 3.0 for 20-μg estrogen pills with levonorgestrel to 14.2 for formulations containing third-generation progestins. Notably, pills containing bioidentical estradiol also demonstrated increased VTE rates.
The researchers employed Danish national registers to conduct their analysis, excluding women with histories of thrombosis, cancer, thrombophilia, liver or kidney disease, infertility treatment, hormone therapy, and several other conditions. The study controlled for multiple variables, including age, calendar year, education, cardiovascular comorbidities, and chronic inflammatory disorders.
Study limitations included potential residual confounding despite extensive controls and limited external generalizability because of the study population's homogeneity and health profile. For patches and implants, the increased VTE risk remained uncertain due to limited data.
The findings remained consistent in sensitivity analyses that exclusively considered confirmed VTE diagnoses and in subcohort analyses adjusting for body mass index, smoking, and family history.
This research builds upon previous studies examining VTE risk in hormonal contraception users while providing new insights into contemporary formulations, including those containing bioidentical estrogen and newer progestins.
The study was supported by Sygeforsikringen "Danmark" (grant 2021-0128), with researchers from multiple Danish institutions including Aalborg University Hospital, Nordsjaellands Hospital, Danish Cancer Institute, and the University of Copenhagen contributing to the research.
Full disclosures can be found in the study.