Long-Term
HRT Does Not Protect the Heart
Long-term
follow-up of HERS II does not support the cardiovascular benefit once
attributed to hormone replacement therapy (HRT).
Long-term
follow-up of the Heart and Estrogen/Progesterone Replacement Study
(HERS II) reported in the July 3 issue of The Journal of the
American Medical Association does not support the
cardiovascular benefit once attributed to hormone replacement therapy
(HRT). Furthermore, HRT was linked to increased risk of venous
thromboembolism and biliary tract surgery.
"This
follow-up study found no reduction in risk of heart attacks or death
for women with heart disease during up to seven years of hormone
therapy," lead author Deborah Grady, MD, MPH, from the University
of California, San Francisco, says in a news release. "Not only
was there no cardiovascular benefit, there were adverse affects,
including blood clots and gallbladder disease."
HERS
was a randomized, blinded, placebo-controlled trial of estrogen plus
progestin in older postmenopausal women with heart disease. Contrary
to expectation, risk of myocardial infarction (MI) increased during
the first year of HRT, although risk seemed to decrease during the
remainder of the study, which lasted 4.1 years. The HERS II follow-up
open-label study, lasting 2.7 years, was therefore designed to
evaluate the effects of longer-duration HRT.
In
HERS, 2763 postmenopausal women with coronary heart disease, average
age 67 years, received either 0.625 mg/d conjugated estrogen plus 2.5
mg medroxyprogesterone acetate, or placebo. During the HERS II
follow-up, the women chose whether to take hormones based on advice
from their personal physicians.
The
initial trend from HERS suggesting a reduced risk of MI with longer
duration of HRT did not persist with additional follow-up. Combining
HERS and HERS II, there was no risk reduction from HRT during almost
seven years.
In
fact, HRT doubled the risk of thromboembolism in the legs and lungs,
with most of the increased risk in the early years of treatment, and
increased the risk of gallbladder disease requiring surgery by 48%.
There was no benefit of HRT for any other major disease outcome
including overall risk of death.
"These
observations confirm the wisdom of 'evidence-based medicine,' basing
treatment decisions on the balance of benefits and harms established
in randomized clinical trials," says co-author Stephen Hulley,
MD, MPH. "Our study indicates that for older women with heart
disease, estrogen plus progestin therapy is not beneficial and does
have some harmful effects."
Funding
for these studies was provided by Wyeth-Ayerst Research.
In
an accompanying editorial, Diana B. Petitti, MD, from Kaiser
Permanente Southern California in Pasadena, agrees that pessimism for
HRT is appropriate but should not cause pessimism for disease
prevention in postmenopausal women. Although other observational
studies touting benefits for HRT are unconfirmed, the focus should
shift to other modalities of demonstrated benefit, such as angiotensin-converting
enzyme inhibitors, aspirin, and blood pressure control to reduce
cardiovascular risk.
"An
appropriately pessimistic view of HRT as an omnibus agent to prevent
disease in postmenopausal women should focus more attention on these
preventive interventions, which have a strong evidence base," she
writes. JAMA.
2002;288(1):49-57, 58-66, 99-101
