HRT drugs increase the Risk of Coronary Heart Disease
JoAnn E. Manson, M.D., Dr.P.H., Judith Hsia, M.D., Karen C. Johnson, M.D.,
M.P.H., Jacques E. Rossouw, M.D., Annlouise R. Assaf, Ph.D., Norman L.
Lasser, M.D., Ph.D., Maurizio Trevisan, M.D., Henry R. Black, M.D., Susan R.
Heckbert, M.D., Ph.D., Robert Detrano, M.D., Ph.D., Ora L. Strickland,
Ph.D., Nathan D. Wong, Ph.D., John R. Crouse, M.D., Evan Stein, M.D., Mary
Cushman, M.D., for the Women's Health Initiative Investigators
ABSTRACT
Background: Recent randomized clinical trials have suggested that estrogen
plus progestin does not confer cardiac protection and may increase the risk
of coronary heart disease (CHD). In this report, we provide the final
results with regard to estrogen plus progestin and CHD from the Women's
Health Initiative (WHI).
Methods: The WHI included a randomized primary-prevention trial of estrogen
plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age
at base line. Participants were randomly assigned to receive conjugated
equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg
per day) or placebo. The primary efficacy outcome of the trial was CHD
(nonfatal myocardial infarction or death due to CHD).
Results: After a mean follow-up of 5.2 years (planned duration, 8.5 years),
the data and safety monitoring board recommended terminating the
estrogen-plus-progestin trial because the overall risks exceeded the
benefits. Combined hormone therapy was associated with a hazard ratio for
CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95
percent confidence interval after adjustment for sequential monitoring, 0.97
to 1.60). The elevation in risk was most apparent at one year (hazard ratio,
1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher
base-line levels of low-density lipoprotein cholesterol were associated with
an excess risk of CHD among women who received hormone therapy, higher
base-line levels of C-reactive protein, other biomarkers, and other clinical
characteristics did not significantly modify the treatment-related risk of
CHD.
Conclusions: Estrogen plus progestin does not confer cardiac protection and
may increase the risk of CHD among generally healthy postmenopausal women,
especially during the first year after the initiation of hormone use. This
treatment should not be prescribed for the prevention of cardiovascular
disease.