Prior to 1996, the use of postmenopausal estrogen was not believed to increase the risk of venous thrombosis. Subsequent studies, particularly the prospective, randomized, double-blind, clinical trial of the Women's Health Initiative, have clearly shown an increase in the incidence and risk of venous thrombosis in postmenopausal women using conjugated equine estrogens with or without medroxyprogesterone acetate. The risk of venous thrombosis in postmenopausal women is also increased by obesity and age. Oral hormone therapy has been used principally for management of menopausal symptoms. Transdermal estrogens have not been used as extensively in the United States but have a significant use in Europe. Recent observational studies have indicated no increased risk of venous thrombosis with use of transdermal estrogens. Norpregnane derivatives have been associated with an increased risk of venous thrombosis, suggesting that progestins may contribute to the increased risk in postmenopausal women using estrogen plus progestin therapy.