Risk of Venous Thromboembolism Associated with Local and Systemic Use of Hormone Therapy in Peri- and Postmenopausal Women and in Relation to Type and Route of Administration

Objective: The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen.

Methods: In this case-control study, conducted in Sweden between 2003 and 2009, we included 838 cases of VTE and 891 controls with a mean age of 55 years. Controls were matched by age to the cases and randomly selected from the population. We used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization.

Results: Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21). In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10).

Conclusions: The risk of VTE risk is higher in users of systemic combined estrogen-progestogen treatment than in users of estrogen only. Furthermore, the risk of VTE was lower for women who used local estrogen than among those using oral estrogen only. Transdermal estrogen only treatment and estrogen for local effect seem not to be related to an increased risk of VTE.