July 12, 2012

By:

THE NIH BILLION DOLLAR WOMEN’S HEALTH STUDY THAT HARMED WOMEN’S HEALTH

           A firestorm in women’s health
erupted on July 9th, 2002 when the NIH prematurely terminated one
arm of their Women’s Health Initiative Study (WHI) because of “increases in breast cancer, coronary heart
disease
(CHD), stroke, and pulmonary
embolism in study participants on estrogen plus progestin compared to women
taking placebo pills. There were noteworthy benefits of estrogen plus
progestin, including fewer cases of hip fractures and colon cancer, but on
balance the harm was greater than the benefit”.

WHI spokespeople cautioned against
all use of hormone therapy after menopause, citing public health concerns. The
nature of this exaggerated, misleading, and sensationalistic announcement was
recognized by an informed few, but missed completely by the media and much of
organized medicine was the fact that except for stroke in older women and blood
clots, the absolute levels of risk and benefit in all WHI outcomes were rare.

The WHI study, planned largely by
cardiologists and epidemiologists to confirm earlier research showing a heart
protective effect of PHT, but without initial input from women’s health experts,
was never designed to investigate menopause. Indeed, symptomatic women were largely
excluded to reduce the likelihood of dropouts. To ensure adequate numbers of
cardiovascular events the majority of the volunteers were women older than 60.

            At
the initiation of the WHI, clinical use of postmenopausal estrogen and
progestogen therapy (PHT) had been mostly limited to treating menopause-related
symptoms in women aged between 40 and 60, and for prevention of bone fractures.
There was a growing tendency to prescribe hormones for prevention of
cardiovascular disease.

             The title of their first report
highlights their immediate misinterpretation of their results: “Risks and benefits of estrogen and
progestin in healthy postmenopausal women”.
Their population was neither
completely healthy, nor simply postmenopausal. Women up to 79 years of age were
started on hormones, something unusual in clinical practice. Had the title been
something like “Risks and benefits of
initiation of estrogen and progestin in women aged 50 to 79 by decade of age
and time since menopause
,” and the WHI investigators strictly interpreted
their results in that way, they would not now be on the defensive. Instead,
many subsequent WHI publications demonstrated some degree of disconnect between
their study objectives and results, and their conclusions, usually embellishing
negative findings at the expense of the positive, and extrapolating findings in
older women to those at perimenopause.

These issues raise serious
questions about the credibility of the WHI writing groups and of the NIH, and
whether one billion dollars was well spent. The absolute risks in the
populations studied, broken down into age groups, are quite revealing. In women
less than age 60, estrogen compared to placebo showed fewer cases of CHD,
strokes, diabetes, breast cancers, fractures, and deaths. The only increased adverse
event was blood clots. Even more striking, their data shows a significant risk reduction
of CHD in women on EPT who were less than 10 years from menopause.

While the WHI data for early
menopausal woman clearly demonstrates that benefits outweigh risks, women
themselves remain fearful of PHT.  Even now, the key WHI investigators are behaving like
the divorced husband who murders his ex-wife, and then claims child custody
because his children have no mother. They demonstrate a persistent need to
control the indications for HT after menopause solely on the basis of their own
publications, ignoring entirely the wealth of other published evidence, their
own data, or that the WHI was never a study about menopause.

             We now face two questions – has women’s
health after menopause been helped or harmed by the way these findings were
presented, and if harmed, what needs to be done to put things right? The real
story of the WHI may turn out to be incalculable damage wrought on younger
peri- and early postmenopausal women who discontinued their therapy in millions
and are now several years beyond menopause and off hormones. Not only did they suffer
through menopause-related symptoms, but the very women who might have been
protected from heart disease, the single biggest killer of women over 50, and
osteoporosis, one of the major causes of long-term disability, are the ones potentially
most damaged by the WHI. Women who discontinued PHT have significantly
increased risk of hip fracture compared with women who continued taking HT,
with estimates of over 43,000 extra bone fractures per year in the USA. The
number of increased cardiovascular events in young women who discontinued ET
may be even more staggering. The WHI results clearly demonstrate no increase in
cardiovascular risk in women aged 50-59, and for the first time ever an
intervention, namely estrogen, has been demonstrated to actually improve the
health of the women’s coronary arteries.

            This
is a remarkable outcome. Given that almost 50% of women will die from
cardiovascular disease, the public health impact of this response could be
enormous.

 “The last nail
in the coffin of hormone therapy,” the mantra often repeated by WHI supporters,
might actually have caused the opposite outcome of what they hoped and
anticipated, an infliction of increased disease and death, and impaired quality
of life on early postmenopausal women.

            After
the entire hullabaloo created by the WHI, current recommendations for
postmenopausal use of PHT are virtually back to where we started. For example,
The North American Menopause Society (NAMS) concludes: “Recent data support the initiation of HT around the time of menopause
to treat menopause-related symptoms and to prevent osteoporosis in women at high
risk of fracture.”
  Yet the
number of prescriptions has dropped by nearly 75% compared to 2002. Many women
who rejected PHT because of fear of cancer and other problems so exaggerated by
the WHI have suffered unnecessarily. Now women with severe symptoms should be
reassured by the current state of knowledge, as should health professionals who
stopped prescribing.

            Questions
need to be raised about the WHI investigators and authors. Why did they not
present the July 2002 data in 10-year subsets? The lead WHI author told the
Wall Street Journal (WSJ) “Our main job
at the time was to turn around the prevailing notion that hormones would be
useful for long-term prevention of heart disease. That was our objective. This
was a worthy objective which we achieved”
.

             This explanation was absurd when other
research showing a protective effect of starting PHT at a younger age was the
catalyst to the initiation of the WHI study itself.

            Given
the enormous damage inflicted on the last generation, what can be done for the
current generation now traversing the perimenopause? The harsh indictment that
a project designed to benefit women’s health has boomeranged mandates urgent independent
scrutiny of key WHI publications to determine whether there was stretching of
the truth. In that case urgent public education steps must be initiated before
even more harm can be inflicted on women’s health.

            It
is too late for the WHI investigators to develop a transparent and
comprehensive summary of their own results – they have quite simply lost the
public trust.

            There
are two obvious and immediate actions to be called for:

1.  The FDA
needs to revisit the black box warnings on postmenopausal hormones.
Specifically, there needs to be a separation of the advisories for estrogen
alone from estrogen and progestogen combined usage.

2.  The
irresponsible approach taken by the NIH in reporting the data, and their
consistent failure to provide a comprehensive final analysis and overview
leaves little alternate but to call for an independent commission, free of
conflicts of interest including with the NIH itself, to do precisely that. A
comprehensive summary of the key WHI overall results should be brought together
in a single white paper.

            Women
progressing through and beyond menopause in the next decade need to be spared
the unnecessary harm inflicted on their sisters of the previous decade, as
resulted from the rush to publication of incomplete and poorly analyzed data by
the Women’s Health Initiative in July 2002.

           

           

Wulf H Utian MD, PhD, DSc, FRCOG, FACOG, FICS

Professor Emeritus, Reproductive Biology, Case Western Reserve
University.

Executive Director Emeritus, The North American Menopause Society

Honorary Past President, The International menopause Society

His latest book is “Change Your
Menopause”
(Utian Press, 2011).

 

Author’s address:

wulf@utianllc.com  

www.utianllc.com

WHO IS WULF UTIAN?

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