Postmenopausal women who have undergone hysterectomy had a reduced
incidence of breast cancer and cardiovascular events after treatment with
conjugated equine estrogens, according to results from the Women’s Health
However, researchers said estrogen did not have any effect on coronary
heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer or
Researchers set out to examine health outcomes associated with
randomization to treatment with conjugated equine estrogens (Premarin, Wyeth)
among women with prior hysterectomy after a mean of 10.7 years of follow-up
through August 2009. In the analysis, 3,778 women were assigned to daily 0.625
mg hormone therapy, whereas another 3,867 were assigned to placebo.
Participants were postmenopausal women aged 50 to 79 years recruited at
40 US locations from 1993 to 1998.
Rates of invasive breast cancer were similar during the intervention
(HR=0.79; 95% CI, 0.61-1.02) and postintervention phases (HR=0.75; 95% CI,
0.51-1.09) of the study. Women in the estrogen group had a statistically
significant lower cumulative incidence of breast cancer compared with the
placebo group, 0.27% vs. 0.35% (HR=0.77, 95% CI, 0.62-0.95).
Incidence of colorectal cancer did not differ between the two groups.
Although the risk for stroke, deep vein thrombosis and pulmonary
embolism were elevated during the intervention phase for women assigned to
estrogen, researchers said the increased risk factor disappeared
postintervention. For all cardiovascular events, the HR was 2.26% in the
estrogen group vs. 2.12% in the placebo group.
Writing in an accompanying editorial, Emily S. Jungheim, MD,
MSCI, and Graham A. Colditz, MD, DrPH, said although these results
show that adverse event rates are low and largely limited to current use of
unopposed estrogen, there does not appear to be a substantial benefit
associated with hormone therapy.
“There may still be a role for short-term use of unopposed estrogen
for treating some women with menopausal symptoms, but this role may be
vanishing as existing and emerging data continue to be better understood in
terms of application to patients,” they wrote. “Despite the evidence
linking unopposed estrogen [hormone therapy] use to breast cancer, many
clinicians and patients make decisions to use hormone therapy. Clinicians must
be aware of the implications of these decisions. They must interpret new and
existing data, and must understand the value and limitations of the data when
It is better to administer estrogen alone if it is necessary to treat
symptoms. Much of the negative effects associated with hormone replacement
therapy are due to the combination of estrogen and progesterone. However, the
idea that giving estrogen alone has overall health benefits for asymptomatic
women isn’t really supported by this study — these results just
suggest that estrogen alone isn’t as bad as estrogen plus progesterone.
Plus, we know estrogen is good for bone health, but there are many other
choices for bone health that have a protective effect for breast cancer, such
as tamoxifen or raloxifene. Estrogen also helps with vaginal dryness, but we
have topical combinations that are associated with less systemic risk. There
are ways other than estrogen to treat a symptom or prevent a disease that do
not carry the same risks.
– Douglas Yee, MD
Director, University of
Minnesota Cancer Center