It's been 10 years since researchers of the Women's Health Initiative, a large randomized, controlled trial on hormone therapy sponsored by the National Institutes of Health, announced their first findings:
The health risks outweighed the benefits of estrogen plus progestin hormone therapy (HT) in postmenopausal women.
Since then, additional research has advanced the understanding of the
benefits and risks. JoAnn Manson, one of the study's lead investigators
and a professor of medicine at Harvard Medical School, is the president
of the North American Menopause Society.
She spoke with USA TODAY's Janice Lloyd about what women need to know
to get through the challenging time and to protect their health.
Q: Millions of women stopped taking hormone therapy as a result of the study 10 years ago. Was that a good thing?
A: Although the pendulum may have swung too far, it
was a good thing that many women who were inappropriate candidates for
HT stopped taking the medications. For example, it was fortunate that
many women at high risk of heart attack, stroke, and breast cancer
stopped taking HT. However, even young, newly menopausal, and healthy
women with significant hot flashes and other symptoms became afraid to
seek treatment. Also, many many clinicians no longer prescribe, or know
how to prescribe. This isn't a good situation for young women who are
having severe menopausal symptoms. They're going to have trouble finding
clinicians who will help them make the most informed decision.
Q: Critics fault the Women's Health Initiative for using
mostly older women who wouldn't benefit from hormone therapy. But what
do you think was one of the biggest takeaways from that study?
A: WHI deserves credit for stopping what was
becoming common practice of starting hormone therapy in older women who
were at high risk for heart disease because we found it failed to
protect them from heart disease, stroke or dementia, and actually
increased their risk. We also learned there are major differences in the
benefit-risk profile of estrogen alone -- used by women who have had a
hysterectomy -- and estrogen plus progestin, used by women who have an
intact uterus. The balance of benefits and risk was more favorable with
Q: Was the study flawed in any way?
A: It's fortunate there was a broad range of age
groups so we could assess differences by age, but unfortunate there were
not more women in the younger age group so we'd have a clearer
understanding of the results for younger women seeking relief from
Q: What has been learned since 2002 about who is most likely to benefit from hormone replacement therapy?
A: It's become very clear that a "one size fits all"
approach is not appropriate. The WHI has pointed the way to more
individualized decision making and healthcare.
Q: Can you describe a woman likely to get the most benefit?
A: She is newly menopausal, within five years of
onset of menopause, and in generally good health and with few risk
factors for heart disease or breast cancer. For example, she would be a
nonsmoker, not obese and does not have diabetes or poorly controlled
blood pressure. That is the optimal candidate. But an optimal candidate
would also have moderate or severe hot flashes, night sweats or other menopausal symptoms, so she'd have a clear indication for treatment. From a breast
cancer standpoint, she would not have first-degree relatives (mother,
sister) with breast cancer and would not be known to have the BRCA1 or
BRCA2 gene. (Women who have inherited mutations in these genes have a
higher risk of developing breast cancer and ovarian cancer.) Even though
that's the optimal candidate, I don't want to suggest that these are
the only women who would benefit from HT or be considered for treatment.
Q: What length of time is safe for HT?
A: We usually advise women and their clinicians to
avoid more than five years of estrogen plus progestin because of the
risk of breast cancer. Estrogen alone did not increase the risk of
breast cancer in the WHI over seven years and may be used for that time
period, or even longer if needed.
Q: What if a woman has mild menopause symptoms but wants to also take it for bone protection?
A: We don't generally recommend a woman start or
continue on HT just for bone protection. The reason is, once you
discontinue estrogen there is accelerated bone loss. If a woman is
taking estrogen in her 50s by the time she gets to her 70s or 80s, when
risk of osteoporotic fracture is greatest, she'll retain only a limited
benefit (from HT). And we wouldn't recommend using estrogen plus
progestin for 20-30 years for bone benefit because that would put women
at increased risk for breast cancer and stroke. Other strategies are
available for bone protection.
Q: If a woman wants to re-evaluate her decision about HRT, how does she get started?
A: The website for the North American Menopause
Society (NAMS) provides a great deal of information for patients and
their clinicians. Finding a good clinician who is up to date on HT
research and has experience prescribing these medications can be a
challenge. The NAMS website (menopause.org) lets people know which
clinicians in their zip code area have extra training and interest in
menopausal issues and are NAMS certified menopause practitioners
Q: What important research is in the pipeline?
A: We need more information on different
formulations and doses of HT. The results of the Kronos Early Estrogen
Prevention Study will be presented at the North American Menopause
Society meeting in October. KEEPS is a study of 727 women who were
within three years of the onset of menopause (42 to 58 years old) when
they enrolled in the HT trial. KEEPS is looking at a number of outcomes,
including whether early estrogen prevents or delays atherosclerosis and
improves cognitive function or quality of life. It's also comparing
different formulations of treatment.