The Heart and Estrogen/progestin Replacement Study (HERS) followed postmenopausal women who had taken estrogen and progestin to evaluate the effects of the hormones. Participants in the randomized, blinded, placebo-controlled trial were followed for 4.1 years before the study was halted. Women who chose to participate in a second study, HERS II, were followed for an additional 2.7 years. Hulley and associates review the noncardiovascular outcomes in women who continued taking hormones during HERS II.
The analyzed outcomes included fracture, cancer, and total mortality. Postmenopausal women younger than 80 years who had coronary artery disease participated in the study. Researchers reviewed hospital records to determine the occurrence of pulmonary embolism (PE), deep venous thrombosis (DVT), biliary-tract surgery, clinical fractures, and cancer.
There were 1,383 women in the HERS placebo group and 1,380 women in the hormone replacement group. Of these, 1,165 women in the placebo group and 1,156 in the hormone replacement group enrolled in HERS II. During HERS, the hormone replacement group had a two- to threefold increase in DVT and PE. During HERS II, there was no longer a statistically significant increased risk of DVT. With any venous thromboembolism, the event rate per 1,000 person-years was 5.9 in women taking hormones and 2.8 in women taking placebo. During HERS, there was a slightly higher relative hazard (1.48) for biliary-tract surgery in the hormone replacement group. The overall rate of surgery was 6.2 per 1,000 person-years higher in the hormone replacement group. Cancer rates were not significantly different in the hormone and placebo groups. The relative hazard for hip fracture was not significantly different between HERS and HERS II, with an overall relative hazard of 1.61 and no decreased fracture risk.
The authors conclude that there was an increased risk of biliary-tract surgery and thromboembolism in women who received hormone replacement therapy. There might be a slight decrease in thromboembolism after the second year of hormone replacement therapy. Other noncardiovascular outcomes were not affected.