Hormone Therapy and Risk of Venous Thrombosis in the Women’s Health Initiative Trial of Estrogen Plus Progestin

October 2004

Findings Summary

Venous thrombosis (VT) occurs when a blood clot or clots form in a vein of a limb (usually in the leg) and produces redness, pain, and swelling in the overlying skin. While it is already known that postmenopausal hormone therapy increases the risk of VT, WHI researchers investigated whether other factors increased this risk. These results were published in the medical journal, JAMA (October 6, 2004).
VT, also called thromboembolic disease, includes deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is the development of a blood clot (thrombus) in the deep veins of the legs, pelvis, or arms. This is also referred to as phlebitis. A PE occurs when clots break free from the vein, travel and lodge in the pulmonary arteries. The clots block blood flow to parts of the lungs, keeping blood from the lung tissue and damaging the tissue. This leads to a decrease in the lungs’ capacity to get oxygen into the blood, which can cause damage to other vital organs and even lead to death. The earliest results from the WHI Hormone Program (reported in July 2002) revealed that during one year, for every 10,000 women taking estrogen plus progestin (E + P), we would expect 18 more women (compared to those taking the placebo) to have blood clots.
The updated results show that after an average of 5.6 years, 167 of the women taking E + P (3.5 per 1000 person years) and 76 (1.7 per 1000 person years) taking placebo pills developed VT, or 18 additional women with VT per year among 10,000 women using E + P. Hormone treatment added to the known risks associated with age, being overweight/obese, and having factor V Leiden*. Based on these findings, careful consideration of the use of E + P in women with these added risk factors is advised. While thinner and younger women (ages 50-59) were at lower risk of VT while using E + P, their risk was still two-fold higher with E + P compared to placebo. In another finding from this paper, regular use of aspirin did not protect women from developing E + P-related venous blood clots.
Women in this trial were randomly assigned to either placebo or estrogen plus progestin (conjugated equine estrogens 0.625 mg and medroxyprogesterone acetate (2.5 mg), also known as Prempro). When the WHI study first began, this was the most commonly prescribed menopausal hormone therapy in the United States for women with a uterus. Because of the overall findings of health risks exceeding benefits, use of these hormones is now generally recommended only for short-term relief of menopausal symptoms.
*Factor V Leiden (factor V mutation) is the most common genetic disorder related to developing VT, and is found in about 5% of persons, mainly those of European descent. In the presence of this particular gene disorder, blood has an increased tendency to clot. People carrying the factor V Leiden gene have a five times greater risk of developing a blood clot than the rest of the population. However, most people with this gene problem will never suffer from blood clots.