PROS AND CONS OF ESTROGEN REPLACEMENT IN POSTMENOPAUSAL WOMEN: WHAT THE
CURRENT EVIDENCE MEANS
Jan Shifren, M.D.*
Harvard Medical School
Massachusetts General Hospital, Boston, MA 02114
Menopause, the permanent cessation of menstruation, occurs at a mean
age of 51 years. Despite a great increase in female life expectancy,
the age at menopause has remained remarkably constant. A woman in the
United States today will live approximately 30 years, or greater than a
third of her life, beyond menopause. The menopausal ovary ceases to
produce significant amounts of estrogen therefore symptoms and diseases
associated with estrogen deficiency are of increasing importance in
women's health.
Options for caring for menopausal women have increased greatly since
estrogen replacement therapy (ERT) was first introduced in the 1960's.
With respect to hormone use, there are many choices of hormone type,
dose, and method of administration. Not only have new forms of
estrogens and progestins been introduced, but novel ways of combining
the two hormones are available. Androgen replacement therapy for older
women currently is being studied as well. In addition to hormones,
selective estrogen receptor modulators are available, as are
bisphosphonates. Women also are requesting more information on
alternative and complementary therapies. The many options now available
make caring for the postmenopausal woman more rewarding, but also a
greater challenge.
Estrogen replacement therapy may play a role in several important
health concerns of postmenopausal women including vasomotor symptoms
and genitourinary atrophy, osteoporosis, cardiovascular disease,
Alzheimer's disease, breast cancer, colon cancer, and sexual
dysfunction. Randomized controlled trials demonstrate that ERT
effectively treats hot flashes and night sweats as well as vaginal
dryness and dyspareunia associated with genital atrophy. Strong
evidence also supports a role for ERT in the prevention and treatment
of osteoporosis, with changes in bone mineral density often used as an
intermediate marker for reduced fracture risk. Observational data
demonstrate a significant reduction in cardiovascular disease and
overall mortality in ERT users, but these findings may be confounded by
healthy user and compliance bias. Favorable changes in lipids and
lipoproteins, as well as effects on vascular reactivity provide
potential biological mechanisms for heart disease risk reduction in ERT
users. With respect to the secondary prevention of heart disease in
postmenopausal women with established disease, randomized controlled
trials of combination estrogen/progestin hormone replacement therapy
(HRT) or ERT alone have not shown a benefit for therapy. Whether there
is a role for HRT or ERT in the primary prevention of heart disease
currently is being studied as part of the Women's Health Initiative.
Although several small observational and controlled studies suggest
that ERT may reduce the risk and slow the progression of Alzheimer's
disease, a large randomized controlled trial of ERT in women with
established disease did not demonstrate any benefit. Whether there is a
role for HRT in the primary prevention of Alzheimer's disease currently
is being studied as part of the Women's Health Initiative Memory
study.
The risks of ERT include an increased risk of endometrial cancer in
women with a uterus who do not use concurrent progestin, an increase in
venous thromboembolic events, gallbladder disease, and a probable small
increased risk of breast cancer in long term ERT/HRT users.
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