A retrospective analysis of data from the Women’s Health Initiative (WHI) published in the Annals of Internal Medicine suggests that combination hormone therapy (HT) increases risk for coronary heart disease (CHD) in healthy postmenopausal women during the first 2 years of use and offers no cardioprotection during the first 8 years of use. The increased risk was statistically significant only among women who began the therapy more than 10 years after menopause, and the results do not apply to women who take estrogen-only hormones following hysterectomy.

The WHI was a double-blind, placebo-controlled, multicenter, primary prevention trial that randomly assigned 16,608 postmenopausal women to once-daily conjugated estrogen 0.625 mg plus progesterone 2.5 mg (n=8506) or placebo (n=8102). In this current analysis, the researchers used WHI data to assess the effect of continuous combination HT on the risk of CHD based on years since menopause. The analysis was adjusted for approximately the 40% of women who stopped use of at least 80% of the assigned treatment by year 6.

Overall, 188 women on continuous combination HT developed CHD, with 80 cases diagnosed during the first 2 years of follow-up. In the placebo group, 147 women developed CHD, with 51 cases in the first 2 years. When compared with women assigned to placebo, the women on continuous HT were approximately 2.4 times more likely to develop CHD during the first 2 years of use (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.55 to 3.62). A trend toward an increased risk for CHD was noted among women receiving HT versus placebo during the first 8 years of use (HR, 1.69; 95% CI, 0.98 to 2.89), indicating that HT did not significantly increase the risk for CHD but also did not protect against it.

Among a subpopulation (n=5494) of women who were within 10 years of menopause at randomization, there were 31 case of CHD (14 in the first 2 years) in the HT group and 34 cases (12 in the first 2 years) in the placebo group. The estimated average HR was 1.29 (95% CI, 0.52 to 3.18) during the first 2 years of follow-up and 0.64 (95% CI, 0.21 to 1.99) during the first 8 years of follow-up. These results demonstrate no statistically significant difference in risk for CHD between the HT and placebo groups. An analysis of CHD-free survival in this subpopulation, however, suggests a significant difference favoring HT after 6 years of use.

The findings of this study are consistent with those from the larger Nurses Health Study, and support current recommendations for women to take hormone replacement therapy as necessary to relieve the symptoms of menopause at the lowest dose and shortest amount of time possible. These findings strengthen the support for the Food and Drug Administration (FDA) recommendations that postmenopausal HT should not be used for the prevention of heart disease.

The WHI is a 15-year research program designed to assess cardiovascular disease, cancer, and osteoporosis in postmenopausal women. The principal findings from the two WHI HT trials found that the overall risks of long-term use of HT outweigh the benefits. Both of these trials were stopped early due to the increased health risks and failure to prevent heart disease, a key question of the studies.

1. Toh S, Hernandez-Diaz S, Logan R, Rossouw J, Hernan M. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial. Ann Intern Med. 2010;152(4):211-217. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/20157135?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=3. Accessed March 8, 2010.

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This entry was posted on Monday, March 8th, 2010 at 12:00 pm.