Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study

Introduction: Because the risk of venous thromboembolism (VTE) associated with progestin is uncertain, we tested oral contraceptives, estrogen and progestin as independent VTE risk factors. Materials and Methods: Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN women with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n = 726) and one to two Olmsted County women per case matched on age, event year and duration of prior medical history (n = 830), and reviewed their complete medical history in the community for previously-identified VTE risk factors (i.e., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, varicose veins and pregnancy/postpartum), and oral contraceptive, oral estrogen, and oral or injectable progestin exposure. Using conditional logistic regression we tested these hormone exposures as VTE risk factors, both unadjusted and after adjusting for previously-identified VTE risk factors. Results: In unadjusted models, oral contraceptives, progestin alone, and estrogen plus progestin were significantly associated with VTE. Individually adjusting for body mass index (BMI) and previously-identified VTE risk factors, these effects remained essentially unchanged except that progestin alone was not associated with VTE after adjusting for active cancer. Considering only case-control pairs without active cancer, progestin alone was positively but non-significantly associated with VTE (OR = 2.49; p = 0.16). Adjusting for BMI and previously-identified VTE risk factors including active cancer, oral contraceptives, estrogen alone, and progestin with or without estrogen were significantly associated with VTE. Conclusions: Oral contraceptives, estrogen alone, estrogen plus progestin, and progestin with or without estrogen are independent VTE risk factors.