An interview with Rowan Chlebowski, MD, a lead investigator
of the Women�s Health Initiative.
Rosenberg: The Women�s
Health Initiative findings about hormone therapy (HT) were definitive enough
that both the estrogen and estrogen plus progestin arms of the study were
terminated. Yet claims of heart and memory benefits for women, if HT is started
early enough, continue in the media. Is there new information that has changed
the risk/benefit ratio?
new information was a secondary analysis of WHI data which ran in JAMA in 2007
and found HT may not be as detrimental for coronary heart disease as previously
thought, if started in early menopause. Risk for stroke did not change,
however, and there are indications that breast cancers appeared earlier, when
hormones were started earlier.
Rosenberg: Why are
some doctors and continuing medical education courses presenting HT as cardioprotective?
claim is heard more from the gynecological community which had been the biggest
HT prescribers rather than from the general medicine or the oncology community.
The FDA has not changed the prescribing label on the basis of the WHI secondary
analysis. HT is still not a desirable chronic disease risk reduction agent
though for short term relief of vasomotor systems like hot flashes no other
therapy comes close.
Rosenberg: Do you
believe the �timing theory� -- that HT has greater benefits than WHI revealed
because women began therapy too late -- will be found to have merit?
course, the timing theory is just a theory. It would require a very expensive
study to investigate. So far, on the basis of secondary analysis from WHI at
seven years, the National Institutes of Health has not indicated an interest in
a new study about timing.
Rosenberg: What about
memory and cognition benefits and the claim that HT could prevent dementia?
Women�s Health Initiative Memory Study which was a sub-study of women 65 or
older found, after four years of HT, all types of dementia doubled in women.
Some of these findings could be related to the increase in stroke that was seen
in this group.
Rosenberg: Why do doctors
still promote HT despite its cancer, heart disease, stroke and blood clot
risks? Are they influenced by drug companies?
Certainly the estrogen drug used in the trials, Premarin, and the estrogen plus
progestin drug Prempro are best selling products of Pfizer, previously Wyeth.
These companies are also big supporters of the gynecology community. It is
reasonable for companies to support groups who use their products so it becomes
a chicken and the egg question. The gynecology community tends to focus more on
heart problems than the data about breast or lung cancer that is increasingly
emerging from WHI.
Rosenberg: Why is WHI
billed as a landmark study? Haven�t a lot of studies looked at these issues
like the PEPI, HERS, the Million Women Study and the Nurses� Health studies?
PEPI study[Postmenopausal Estrogen/Progestin Interventions Trial] largely
investigated estrogen�s effect on the uterus and led to WHI�s addition of a
progestin to estrogen to prevent endometrial cancers. The HERS study[Hormone
Therapy Estrogen Cardiovascular Protection Clinical Trials] looked at women
with established coronary heat disease and found no beneficial effect of HT
looking at cardiovascular end-points. The Million Women Study in the UK is an
observational study and the Nurses� Health Study also is an observational study
at Harvard of younger women. The WHI trial is the only fully powered
randomized, placebo controlled trial able to address the most frequent causes
of death and disability in postmenopausal women -- cardiovascular disease,
cancer, and osteoporosis.
Rosenberg: Critics of
WHI say the large numbers of women who stopped taking estrogen and progestin or
who took them when assigned placebo invalidate its status as a random
adherence rates were similar to those seen in other prevention large trials. When
the intervention ended, after five and a half years, about 60 percent of women
were still adhering to their study medication.
delivered an abstract at the annual San Antonio Breast Cancer Symposium in
December about the bisphosphonate bone drugs some women now take in lieu of
long-term HT to prevent osteoporosis. What about HT�s other clear benefit -- reduction
of the risk of colon cancer?
data do demonstrate that HT lowers the risk of colon cancer. However those
colon cancers that do develop tend to be more advanced and we are exploring
why. This is why you haven�t heard the colon cancer figures emphasized much.
Rosenberg: The New
York Times reporter Tara Parker-Pope reported that there was internal discord
at WHI over stopping the trials. Is that true?
was no disagreement with the estrogen plus progestin discontinuation but there
was a difference of opinion about the decision to stop the estrogen alone trial
because the risks appeared less. Of course these decisions are not made by the
investigators but by data safety panels and external advisory committees.
Rosenberg: WHI has 40
centers and hundreds of researchers. How did you become first author on so many
used to think you had to be the meanest of the bunch to be first author, but
evidently not. (laughs) First authorship decisions are made from
recommendations by a WHI Publication and Presentation Committee of those able
-- and willing -- to do it. I believe the reason I have been asked to lead
several cancer papers is that I am a medical oncologist and have published
quite extensively about breast cancer and hormones. I�m grateful to the entire
WHI team of investigators for their support.
Rosenberg: So as an
oncologist and the �face� of WHI for several years, do you tell women to not
take HT -- except for very short-term use?
Unless you have limiting climacteric symptoms (hot flashes, sexual difficulty),
when you look at the emerging cancer data, is this really something you want to
Martha Rosenberg is a Chicago
columnist/cartoonist who writes about public health. She may be reached at firstname.lastname@example.org.