Robert A.

Wascher, MD, FACS

Breast Cancer Recurrence & Hormone Replacement Therapy (HRT); Carotid Artery
Disease: Surgery vs. Stents?; Statin Drugs & Cancer Prevention

2008-04-13 at 12:48 pm · Filed under Culture, Family, Health, North America, Science &
Nature, Society, VOA, Vox Populi

The information in this column is intended for informational purposes only, and
does not constitute medical advice or recommendations by the author. Please
consult with your physician before making any lifestyle or medication changes, or if
you have any other concerns regarding your health.

BREAST CANCER RECURRENCE & HORMONE REPLACEMENT THERAPY

(HRT)

Regular readers of this column are already well informed about the known risks
associated with taking hormone replacement therapy (HRT) to relieve the symptoms of
menopause. With the results of the landmark Women’s Health Initiative Study (WHIS),
and similar studies, clearly implicating combination HRT with an increased risk of breast
cancer, heart disease, stroke, dementia, and other serious illnesses, physicians and their
patients are, increasingly, taking a more conservative approach to dealing with the
unpleasant symptoms that often accompany the onset of menopause.

Among women who have previously been diagnosed with breast cancer, the risk of
developing a recurrence of their cancer, and new breast cancers as well, is known to be
higher than for women of otherwise average breast cancer risk, and with no prior history
of breast cancer.

Up until now, there has not been a great deal of research data looking specifically at the
added risk, if any, of taking HRT after a prior diagnosis of breast cancer, although most
experts believe that HRT is almost certainly a risk factor for breast cancer recurrence
(i.e., in addition to the development of new cancers in the breast). Now, a new study,
from multiple university medical centers in Europe, looks at the impact of HRT in breast
cancer recurrence among women with a prior history of this form of cancer. This new
research study, just published in the Journal of the National Cancer Institute, is part of a
prospective study, called the HABIT Study, which consisted of 442 Scandinavian breast
cancer survivors. A total of 221 women were randomized to receive HRT, while the
remaining 221 women were randomized to no HRT at all.

The results of this study were quite striking. Among the 221 women taking HRT, just
over 22% of these women were estimated to develop recurrent breast cancer after an
average of 5 years of follow-up. Among the 221 women who did not take HRT, only 8%
went on to develop a recurrence of their previous breast cancer at 5 years. This
represents a nearly two-and-a-half fold increase in the risk of breast cancer associated
with the use of HRT and, with respect to the natural history of breast cancer recurrence,
within a rather short period of time as well. In fact, because the risk of recurrent breast
cancer appeared to be so high in the group of women taking HRT, this research study was
prematurely halted in 2004 (just as the WHIS was prematurely terminated in 2002) , and
the women taking HRT were warned about the apparent increased risk of breast cancer
recurrence associated with taking HRT.

As multiple other previous studies have shown, and as I and other breast cancer experts
have warned for years, the use of HRT (and combination HRT in particular) appears to
have significantly contributed to the decades-old gradual rise in the annual number of
breast cancer cases diagnosed in the United States since the mid-1960s, when HRT
became especially popular in the U.S. and in other western countries around the world.
The striking and unprecedented recent decline in the annual incidence of breast cancer in
the United States, and in other western countries, following the publication of the
preliminary results of the WHIS in 2002, has paralleled the declining number of
prescriptions written for HRT since this landmark study was published in the Journal of
the American Medical Association. Ironically, I wrote a book on this very topic
(including the shameful history of misrepresentation, and the covert financial and
marketing support provided to pro-HRT physicians, by the dominant pharmaceutical
manufacturer of HRT drugs in the mid-1960s, and thereafter) in 2004. However, the
majority of senior publishing house editors who reviewed the manuscript (most of whom
were women, it must be said) dismissively accused me of being “biased” against HRT;
and several opined that, as a man, I simply could not understand the ravages of
menopause and, hence, the quality-of-life improvement brought about by HRT
medications (notwithstanding decades of clinical research showing that only 2-5% of
women experience profoundly disabling symptoms associated with menopause, and in
the majority of all women passing through menopause, these symptoms significantly and
spontaneously abate within 3-5 years).

The results of this new study are completely consistent with what we now know about the
molecular biology of estrogen and progesterone (the primary female sex hormones), and
their stimulatory effects on the proliferation of breast cancer cells (the overwhelming
majority of breast cancers, especially in women aged 50 and older, have chemical
receptors for these sex hormones, which stimulate these cancer cells to grow and divide).
My advice to all women, and especially to women with a prior history of breast cancer, is
to avoid HRT drugs, period. This has been my consistent recommendation for the past
20 years, based upon clinical research and observations dating back to the 1930s. With
the enormous amount of confirmatory data that has been subsequently published since
2004, I don’t appear to be the one with significant biases in this area….

CAROTID ARTERY DISEASE: SURGERY VS. STENTS?

A relatively common manifestation of peripheral arterial atherosclerotic disease

(“hardening of the arteries”) is carotid artery stenosis. The carotid arteries supply most of
the blood to the brain, and when they become clogged with atherosclerotic plaque and
blood clots, bits of these materials can break off (or embolize) and lodge in the smaller
arteries that feed the brain, causing temporary or permanent damage to the brain. These
embolic complications of carotid artery disease are referred to as, respectively, transient
ischemic attacks and strokes (the same vascular disease process occurs in the coronary
arteries, and leads to heart attacks, or myocardial infarctions).

Nearly 150,000 operations for carotid artery stenosis are currently performed each year in
the United States, as there is abundant research evidence supporting surgical over
medical treatment in patients with significant narrowing of their carotid arteries (the
primary risk of untreated carotid artery stenosis is stroke). In this operation, the clogged-
up, narrowed artery is surgically opened, and the surgeon then carefully peels the
thickened, diseased lining away from the wall of the artery, leaving a clean surface
behind. The artery is then sewn shut (often, a synthetic patch is also used to reconstruct
the artery, to prevent narrowing of the artery). This operation, referred to as carotid
endarterectomy, is not without risk (as with any operation), however, and is associated
with a 0.5-2% risk of postoperative stroke, as well as a small risk of bleeding, infection
and death.

A relatively recent innovation in the management of arterial atherosclerotic disease has

involved the use of shunts, most of which can be placed through small, superficial
incisions in the groin or arm, much as cardiologists and interventional radiologists have
been doing for decades in order to perform x-rays studies of the arterial system
(“angiography”), and more recently, to treat diseased coronary arteries with balloon
catheters and stents. This minimally-invasive approach to atherosclerotic vascular
disease has revolutionized the management of not only coronary artery disease, but also
for aneurysms (abnormal dilation of atherosclerotic arteries) of the aorta (the largest
artery in the body), and the large branch arteries that arise from the aorta to supply the
lower extremities (the iliac and femoral arteries). However, given the potentially
catastrophic complications (including death) associated with strokes, the use of balloon
catheters and stents to treat narrowed areas of the carotid arteries has not advanced as
rapidly as it has for other diseased arteries in the body.

A new study from Harvard University, and several other collaborating U.S. medical
centers, and just published in this week’s New England Journal of Medicine, provides
important clinical data to suggest that minimally invasive carotid artery stenting may
finally have become at least the equal of carotid endarterectomy, at least in highly
selected patients. In this prospective randomized clinical study, a total of 334 patients
with narrowed carotid arteries were randomized to either standard surgical treatment (i.e.,
carotid endarterectomy) vs. carotid artery stenting. The average follow-up of these
patients was 3 years.

Altogether, almost 80% of the patients participating in this clinical trial were available for
follow-up evaluation after 3 years. The bottom line: patients in both treatment groups
experienced a statistically equivalent incidence of stroke, myocardial infarction and death
(the average incidence of any of these three complications in both groups of patients, at 3
years, was 27%).

This study will likely be considered a landmark research trial regarding the optimal
management of severe carotid artery stenosis, especially in patients who are considered to
be at very high risk of complications following traditional surgical intervention. The use,
in this study, of a special device designed to catch errant bits of clot and plaque that
might be dislodged during placement of the stent very likely helped to achieve the
excellent results reported in this high-quality research trial, and sets this study apart from
some earlier studies that did not use such “anti-embolization” devices (and which often
reported prohibitive stroke rates associated with carotid artery ballooning and stenting).

As a reminder to my readers, the risk factors most commonly associated with carotid
artery atherosclerosis (and, indeed, with atherosclerosis throughout the body) include
smoking, elevated cholesterol and fat levels in the blood, obesity, a sedentary lifestyle
and high blood pressure. Given that an ounce of prevention is worth far more than a
pound of cure when it comes to your health, if you currently have any of these risk
factors, then please see your physician soon, and modify your lifestyle to eliminate (or
control) these risk factors.

STATIN DRUGS & CANCER PREVENTION

There continues to be a great deal of debate regarding the class of cholesterol-lowering

drugs referred to as statins, and their effects (if any) on lowering the risk of developing
certain cancers. In addition to their potent ability to reduce the levels of so-called “bad
cholesterol” (LDL) in the blood, and to increase the levels of “good cholesterol” (HDL),
most statins appear to have at least mild anti-inflammatory effects as well. (Chronic
inflammation in the body has been linked both to the development of atherosclerotic
narrowing of the arteries in our bodies as well as to the development of many cancers.)
Multiple prior laboratory and clinical research trials have generated conflicting data
regarding the effects of statin drugs on cancer risk, with some studies showing a
reduction in the risk of at least certain types of cancer with prolonged statin use, and
other studies showing no apparent cancer-prevention benefit at all.

A newly published study, in The American Journal of Medicine, provides results that
suggest, as other recent studies have, that there may actually be a small, but significant,
cancer-prevention effect associated with at least some of the statin drugs. This study,
from Quebec, Canada, was based upon a large public health clinical data registry, and
looked at patients aged 45 years and greater, between 1998 and 2004, who had survived a
heart attack, and had been prescribed a statin drug as a results of their heart attack. Four
statin drugs within the so-called “lipophilic class” (atorvastatin, simvastatin, lovastatin
and fluvastatin) were specifically included in this retrospective research study. More
than 30,000 patient histories were evaluated in this large public health study, including
more than 18,000 patients who were never prescribed a statin drug, 6,015 patients who
received high-dose statin medications, and 5,323 patients who were prescribed low-dose
statin medications.

After an average of 7 years of follow-up, this study determined that the high-dose statin
users, when compared to patients not taking any statin drugs, experienced a 25%
reduction in the likelihood of admission to a hospital with a new diagnosis of cancer.
The low-dose statin users also appeared to experience a reduction in hospital admissions
related to the diagnosis of cancer, with a more modest 11% reduction in the incidence of
admissions for cancer. Unlike similar recent clinical studies that have shown that only
prolonged statin use may be associated with a reduction in the risk of developing cancer,
this particular study found that even relatively short durations of statin usage appeared to
be associated with a reduced risk of being admitted to a hospital with a new diagnosis of
cancer, especially among patients receiving higher doses of these medications.

This study offers some further encouragement to those who believe that at least some
statin drugs may be associated with the incidental benefit of reducing the risk of cancer.
However, I think that the jury is still out on this one, for now anyway. As with most
retrospective studies based upon public health databases, there are many potential sources
of bias in retrospective epidemiological studies such as this one. Unlike randomized,
prospective controlled studies, which seek to control as many potentially confounding
variables as possible up front, retrospective studies are far more prone to bias, which can
lead to erroneous conclusions.

At this time, I would not recommend that anyone take a statin drug primarily to reduce
their risk of cancer. However, if you are already taking a lipophilic statin for elevated
cholesterol levels, then there is at least the possibility that you may be receiving an
additional health benefit from your statin drug. Obviously, a prospective, randomized,
placebo-controlled study of statins would have to be done to definitively answer the
question regarding statins and cancer risk. Until such a study is performed, we cannot be
completely certain that statins really do reduce the risk of cancer.
 The HRT Titanic: Are you going down
with it?
It's not too late to jump ship!

HRT (Hormone Replacement Therapy) is a key element of modern medical wizardry. It has been
purported for several decades that many female disorders can be minimized or controlled by
supplementing two key hormones in the body. However this treatment is not all that it’s cracked
up to be!

THE EVOLUTION OF HRT

When this type of therapy was first introduced, it was called "Estrogen Replacement Therapy" in
reference to the sole use of estrogen hormones. Within a short period of time the medical
establishment realized that a serious oversight had been made. It was evident that estrogen was
not alone in its impact on female disorders such as menopause and PMS. Research had shown
unmistakably that ERT was in fact increasing the prevalence of breast, ovarian and uterine
cancers. Soon after it was realized that the hormone progesterone was linked to estrogen and it’s
effects in the body. So the medical community began packaging progestin (synthetic
progesterone) together with estrogen to become what we know today as HRT. Interestingly
enough, the same synthetic components are packaged together as the Pill, with the same side
effects.

HOW THE BODY REACTS TO DRUGS

There is an important factor to consider when examining the effectiveness of any drug treatment.
All drugs are synthetic. Naturally occurring substances such as hormones cannot be patented
and since patenting is the very foundation of the pharmaceutical industry, only synthetic versions
of natural substances are ever produced by drug companies.

The problem with synthetic substances is that the body treats them all in the same way; as an
invader. The immune system is designed to detect unnatural substances that enter the body and
attack them. For this reason, drugs can only do damage to the body. This might sound like an
extreme statement to make, however it has to be acknowledged by even the most astute doctor
that all any drug can do is deactivate a natural function in the body. The only thing that makes a
drug effective is when it is targeted against a natural function which may be regarded as
detrimental to the body. Unfortunately however, the former problem remains, that the body treats
all unnatural substances as a threat and consequently goes all out to neutralize or expel the
invader. This invariably leads to a strain on various parts of the body, typically the kidneys and
cardio-vascular system. A quick check of the documented side effects of many commonly
prescribed drugs will confirm that the most affected organs are the heart and the kidneys. It’s
ironic that by supposedly fixing one problem in the body, other equally important parts of the body
are under greater risk of breakdown from the toxic effects of drugs.

INCREASED RISK OF CANCER

Returning to the use of synthetic hormones, it doesn’t take too much intelligence to figure out that
they cannot possible have a beneficial effect in the long run. It has been proven that progestin
also increases the risk of breast, uterine and ovarian cancers whether it is taken alone or in
conjunction with estrogen as a part of HRT. How then can the medical establishment justify the
continued prescription of such dangerous drugs? Simple! They appear to alleviate some of the
symptoms of menopause. We will examine this in more detail later.
MENOPAUSE SYMPTOMS
It is widely accepted that menopause is a part of every woman’s experience, along with all the
unpleasant symptoms associated with it. Yet a quick check into the statistics will reveal that there
are many countries in which the typical symptoms of menopause are rare! In Japan for example,
menopause is rarely heard of. It is interesting to note also that in Japan breast cancer is likewise
rarely seen. What a contrast to our Western society where it is claimed that the highest risk of
breast cancer is being a woman and being over fifty years of age! The medical community still
tenders genetic predisposition as the most common factor in breast cancer, yet the statistics tell
an entirely different story. Nine out of every ten women diagnosed with breast cancer have no
prior family history of the disease! With the incidence of breast cancer on the rise, questions need
to be asked about the validity of the explanations offered by the medical community.

MEDICAL RESEARCH
In actual fact a very recent series of high profile studies at Harvard University have confirmed
what we have suspected for many years already, that HRT does increase the risk of cancer
especially in women who take it for five years or more.

One question remains to be answered then. The medical education system persists in
recommending the prescription of HRT to menopausal women for the purported reason that it can
relieve the symptoms of menopause and also protect against osteoporosis. We’ll deal with
osteoporosis later. But first we must ask, why it is that these synthetic hormones appear to
alleviate the symptoms of menopause? In answering, we must delve a little deeper into the
function of progesterone in the body.

PROGESTERONE
Progesterone is recognised as a pro-hormone, meaning that other hormones are synthesized
from it upon demand. In fact progesterone is at the very root of the hormone tree and is the
primary basis for all steroid hormones. It goes without saying that if such an important hormone is
depleted, all other dependent hormone levels will also begin to dwindle. Progesterone plays a
much more significant role than this though. It is also known as a firelighter hormone, meaning
that it activates many other hormones and allows them to do their job correctly. One of the
hormones it activates is estrogen. It shouldn’t take much to figure out that any retardation in the
function of estrogen could result from lower than normal progesterone levels. In fact this is usually
the case.

At menopause, progesterone levels in a woman’s body drop to zero, signalling the cessation of
regular cycles amongst other things. Contrary to medical opinion, estrogen levels do not fall too
low, but only drop by around 50%. However at menopause, progesterone levels do fall to zero.
With little or no progesterone then, the symptoms which commence around menopause are
understandably mistaken for a sign of low estrogen, because it is progesterone which is
responsible to activate estrogen. But that’s not the only factor. Women all over the world
experience the same hormonal changes, but not all women experience the symptoms normally
associated with menopause. So the natural change in hormone levels is not the major factor.

ESTROGEN MIMICS
Enter a new problem! Estrogen mimics. Otherwise known as xeno-estrogens, these are by-
products of the petro-chemicals used so extensively in our western society. Perhaps the greatest
use of such petro-chemicals is in plastics. Name one person who can survive without the use of
plastics on a day to day basis. The problem is that xeno-estrogens find their way inevitably into
the body and act similarly to natural estrogen. In order for the body’s natural hormones to remain
balanced and functioning correctly, progesterone is needed as we’ve already mentioned. If then
progesterone levels become comparatively lower than estrogen (natural or synthetic), all the
negative effects of estrogen kick in, including weight gain, water retention, cancer risk, dramatic
mood swings, hot flushes and so the list goes on. Sounds like a typical woman’s experience of
menopause doesn’t it! Pity, because it shouldn’t be. Menopause is a time of change, not a
disease. The symptoms popularly associated with menopause are in fact symptoms of estrogen
dominance and can be minimized by ensuring that estrogen levels remain in balance with
progesterone.

OSTEOPOROSIS
We mentioned osteoporosis earlier in relation to claims by the medical community that HRT
protects women against this debilitating disorder. Osteoporosis is where the bones become brittle
and fragile, more easily broken and fractured. It is common to hear of elderly women having to
undergo a traumatic hip replacement because of osteoporosis. The tragedy here is that again the
cause of osteoporosis is not well enough understood. Contrary to popular advertising,
osteoporosis is not a calcium deficiency in the vast majority of cases. Also, contrary to popular
medical opinion, estrogen is not related to the maintenance of bones in any way. The vital link is
actually progesterone again. Surprise, surprise! Progesterone in its firelighting role activates
osteoclast cells and osteoblast cells which are responsible for the removal of old bone and the
formation of new bone respectively. Low progesterone levels are an open invitation for
osteoporosis. The only way in which estrogen can have any bearing on osteoporosis is when it is
comparatively dominant, in which circumstance neither the osteoclast or osteoblast cells do their
job and the progression of osteoporosis may be slowed somewhat. In the long run more damage
is being done.

THE SOLUTION
Due to the prevalence of xeno-estrogens in our environment and food chain, it is improbable that
any of us can escape estrogen dominance entirely. However we can limit it by ensuring our diet
is rich in phyto-estrogens (found in many plants), avoiding the use of synthetic hormones (HRT
and the Pill) and if necessary, consider taking a natural or precursor hormone supplement. By
supplying the body with specific nutrients we can rest assured that our hormones are less likely to
become imbalanced and consequently afford ourselves the greatest protection against hormone
related disorders including osteoporosis and estrogen dominance. One of the most potent and
successful supplements for combating the curse of estrogen dominance is found in the humble
yam of which a considerable deal has been written lately. But more of that in another article.
Bio Identical Hormone Replacement Therapy
"We Age Because Our Hormones Decline.
Our Hormones Don’t Decline Because We Age."

Aging is Directly Related Explaining the Research

to AHDS on HRT

An Introduction to Who is a candidate

BioIdentical HRT for HRT?

The History Assess your risk: Submit a Free

of HRT on-line risk stratification profile

Research Supporting What does Human Growth Hormone

HGH (HGH) do ?

Press Release: Endocrine Society shows no excess risk with HRT

Listen to Age Management expert, Dr. Seema Patel on Sky Radio

Aging is Directly Related to AHDS

Adult Hormone Deficiency Syndrome [AHDS]
comprises the symptom complex routinely
associated with the aging process including
diminished sex drive, mood swings, fat
accumulation, muscle reduction, memory loss,
tiredness, bone degradation, undesirable
changes in skin elasticity, collagen
accumulation and joint flexibility, and
conditions related to an aging immune system.
The positive effects of Bio Identical Hormone
Replacement Therapy [HRT] on the symptom
complex of AHDS has been documented in the
traditional medical literature including Harvard
University, Mayo Clinic, and many other
prestigious research institutions.

Hormone imbalances can cause hot flashes, weight gain, night sweats, etc. Many
hormone creams, pills, and potions on the market are purchased and used
indiscriminately. A more scientific way to deal with the regulation of hormones,
however, is to measure their levels by lab testing and then design a nutrition and hormone
replacement program to bring the levels to normal. The hormones measured include all
the ovarian, adrenal, thyroid, and pituitary hormones, including growth hormone. Those
needing hormone replacement are given bioidentical formulations that can be filled by a
compounding pharmacy. Both women and men can be tested and treated.Natural or Bio
Identical Hormone Replacement Therapy can replace the hormones your body normally
losses with identical hormones at levels when you were in your twenties.

Bioidentical hormones exactly mimic the structure and function of the hormones inside
your body. Bioidentical hormones come from plant sources, and help patients rebalance
hormone levels in their bodies in a natural way.

Benefits
The benefits of medically supervised HRT which may include, testosterone, estrogen,
progesterone, thyroid, DHEA, melatonin, human growth hormone (hGH) and others often
include a decrease in body fat, an increase in energy, including sexual energy, and an
increase in lean muscle, thickening of the skin with decreased wrinkling, improvement in
the cholesterol profile, an increase in bone density, enhanced feeling of well being,
improvement in aerobic capacity, enhanced immune function and a decrease in the
frequency of illness.
Individuals decide to become patients to increase their energy level, including sexual
energy, reduce body fat, increase lean muscle, improve cognitive function, lower
cholesterol, enhance mood, improve ability to handle stress, and strengthen the immune
system so as to remain as disease free as possible. Medically supervised Hormonal
Replacement Therapy by trained Age Management Physicians help patients achieve their
goals.

Personalized Anti-Aging Therapy Programs

Anti Aging programs include personalized and customized recommendations for diet,
exercise, and nutritional and antioxidant supplementation in addition to HRT. The
program will also monitor your response to hormonal and nutritional augmentation and
supplement. The goal of each individualized treatment program is to improve your
overall health and well being, help you to look and feel years younger, prevent disease,
and of course, delay the aging process.
1. An HRT Trained Physician is Important
2. Your physician has also been trained at the world famous Cenegenics Institute.
He will be employing several evaluation techniques and including a complete
health evaluation designed to create your personalized Age Management
Evaluation.
The Lab Tests, your medical and family history, any recent diagnostic medical
procedures, and the results of your most recent primary health care provider physical,
combined with the Health Evaluation Process establishes your hormonal and metabolic
"baseline". This medical information is necessary to design your individualized program,
achieve your goals and enhance the quality of your life as well as to prevent premature
disability and death.
Confusing Research on HRT and the WHI Study

The findings of numerous studies on hormone replacement therapy (HRT) conflict and,
as a result, have raised serious questions regarding the appropriateness of HRT. Hormone
replacement is an approved therapy for relief from moderate to severe hot flashes and
symptoms of vulvar and vaginal atrophy. Numerous studies have confirmed that estrogen
replacement decreases the risk of colon cancer, estrogen and progesterone decrease
fracture risk, and various hormones increase energy levels and enhance libido. Reputable
sources offer conflicting reports regarding issues such as memory, Alzheimer's disease,
and stroke.

With the exception of the Postmenopausal Estrogen/Progestin Intervention (PEPI) study,

major studies have either failed to distinguish among types and dosages of HRT used in
the study, or examined only the use of synthetic HRT preparations (as in the case of the
Women's Health Initiative). The Women's Health Initiative (WHI) study was designed to
identify the potential risks and benefits of HRT. The estrogen-progestin portion of the
clinical trial was stopped in 2002 after results showed that a synthetic hormone
combination containing conjugated equine estrogens (CEE) plus medroxyprogesterone
acetate (MPA) increased the women's risks of developing invasive breast cancer, heart
disease, stroke, and pulmonary embolism. The data and safety monitoring board
concluded that the risks outweighed the evidence of benefit for fractures and colon
cancer. Utilizing data from the WHI, researchers later concluded that synthetic CEE plus
MPA does not improve mental functioning and may increase the risk of dementia in
women over age 65. They suggest these hormones increase the risk of stroke, which is
known to increase the risk of dementia. With regard to the risk of dementia, typical HRT
users are in their 50s and the WHI study focused on women aged 65 and over, who have
a higher risk for dementia. The "estrogen-only" portion of the WHI study was halted in
March 2004 after analysis of data suggested that synthetic CEE alone had no impact
either way on heart disease (the main focus of the study), but may increase the risk of
stroke.

Many patients and medical professionals are unaware of the availability of bio-identical
alternatives. In reality, women's experiences and clinical outcomes of HRT differ vastly
depending on the dose, dosage form, and route of administration, and most importantly,
whether the hormones are synthetic or bio-identical. As a result of concerns and doubts
generated by studies that use synthetic hormones, many women who could substantially
benefit from bio-identical hormone replacement may never have the opportunity.

Published research delineating the differences between natural bio-identical and synthetic
HRT is now more abundant, but studies of bio-identical HRT will probably never be as
plentiful as those dealing with patented synthetic hormones. Our pharmacy welcomes
your questions.
MAJOR RECOMMENDATIONS

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations (A, B,
C, D, or I) and the quality of the overall evidence for a service (good, fair, poor). The
definitions of these grades can be found at the end of the "Major Recommendations"
field.

The USPSTF recommends against the routine use of combined estrogen and progestin for
the prevention of chronic conditions in postmenopausal women. D recommendation

The USPSTF found good evidence that the use of combined estrogen and progestin
results in both benefits and harms. Benefits include reduced risk for fracture (good
evidence) and colorectal cancer (fair evidence). Combined estrogen and progestin has
no beneficial effect on coronary heart disease and may even pose an increased risk (good
evidence). Other harms include increased risk for breast cancer (good evidence), venous
thromboembolism (good evidence), stroke (fair evidence), cholecystitis (fair evidence),
dementia (fair evidence), and lower global cognitive function (fair evidence).

Because of insufficient evidence, the USPSTF could not assess the effects of combined
estrogen and progestin on the incidence of ovarian cancer, mortality from breast cancer
or coronary heart disease, or all-cause mortality. The USPSTF concluded that the
harmful effects of combined estrogen and progestin are likely to exceed the chronic
disease prevention benefits in most women.

The USPSTF recommends against the routine use of unopposed estrogen for the
prevention of chronic conditions in postmenopausal women who have had a
hysterectomy. D recommendation

The USPSTF found good evidence that the use of unopposed estrogen results in both
benefits and harms. The benefits include reduced risk for fracture (good evidence).
Harms include increased risk for venous thromboembolism (fair evidence), stroke (fair
evidence), dementia (fair evidence), and lower global cognitive functioning (fair
evidence). There is fair evidence that unopposed estrogen has no beneficial effect on
coronary heart disease.

Because of insufficient evidence, the USPSTF could not assess the effects of unopposed
estrogen on the incidence of breast cancer, ovarian cancer, or colorectal cancer as well
as breast cancer mortality or all-cause mortality. The USPSTF concluded that the
harmful effects of unopposed estrogen are likely to exceed the chronic disease prevention
benefits in most women.

Clinical Considerations

• The balance of benefits and harms for a woman will be influenced by her personal
preferences, her risks for specific chronic diseases, and the presence of
menopausal symptoms. A shared decision-making approach to preventing chronic
 diseases in perimenopausal and postmenopausal women involves consideration of
individual risk factors and preferences in selecting effective interventions for
reducing the risks for fracture, heart disease, and cancer. Other USPSTF
recommendations for prevention of chronic diseases (screening for osteoporosis,
high blood pressure, lipid disorders, breast cancer, and colorectal cancer; and
counseling to prevent tobacco use) are available at
www.preventiveservices.ahrq.gov.
• The USPSTF did not consider the use of hormone therapy for the management of
menopausal symptoms, which is the subject of recommendations by other expert
groups. Women and their clinicians should discuss the balance of risks and
benefits before deciding to initiate or continue hormone therapy for menopausal
symptoms. For example, for combined estrogen and progestin, some risks (such
as the risks for venous thromboembolism, coronary heart disease [CHD], and
stroke) arise within the first 1 to 2 years of therapy, and other risks (such as the
risk for breast cancer) appear to increase with longer-term hormone therapy. The
populations of women using hormone therapy for symptom relief may differ from
those who would use hormone therapy for prevention of chronic disease (e.g., age
differences). Other expert groups have recommended that women who decide to
take hormone therapy to relieve menopausal symptoms use the lowest effective
dose for the shortest possible time.
• Although estrogen alone or in combination with progestin reduces the risk for
fractures in women, other effective medications (e.g., bisphosphonates and
calcitonin) are available for treating women with low bone density to prevent
fractures. The role of chemopreventive agents in preventing fractures in women
without low bone density is unclear. The USPSTF addressed screening for
osteoporosis in postmenopausal women in 2002.
• Unopposed estrogen increases the risk for endometrial cancer in women who have
an intact uterus. Clinicians should use a shared decision-making approach when
discussing the possibility of using unopposed estrogen in women who have not
had a hysterectomy.

Definitions:

Strength of Recommendations

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations
according to one of five classifications (A, B, C, D, or I), reflecting the strength of
evidence and magnitude of net benefit (benefits minus harms).

The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians
provide [the service] to eligible patients. The USPSTF found good evidence that [the
service] improves important health outcomes and concludes that benefits substantially
outweigh harms.
B

The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians provide
[the service] to eligible patients. The USPSTF found at least fair evidence that [the
service] improves health outcomes and concludes that benefits outweigh harms.

The U.S. Preventive Services Task Force (USPSTF) makes no recommendation for or
against routine provision of [the service]. The US Preventive Services Task Force found
at least fair evidence that [the service] can improve health outcomes but concludes that
the balance of benefits and harms it too close to justify a general recommendation.

The U.S. Preventive Services Task Force (USPSTF) recommends against routinely
providing [the service] to asymptomatic patients. The USPSTF found at least fair
evidence that [the service] is ineffective or that harms outweigh benefits.

The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is
insufficient to recommend for or against routinely providing [the service]. Evidence that
[the service] is effective is lacking, of poor quality, or conflicting and the balance of
benefits and harms cannot be determined.

Strength of Evidence

The U.S. Preventive Services Task Force (USPSTF) grades the quality of the overall
evidence for a service on a 3-point scale (good, fair, or poor).

Good

Evidence includes consistent results from well-designed, well-conducted studies in

representative populations that directly assess effects on health outcomes.

Fair

Evidence is sufficient to determine effects on health outcomes, but the strength of the
evidence is limited by the number, quality, or consistency of the individual studies;
generalizability to routine practice; or indirect nature of evidence on health outcomes.

Poor
Evidence is insufficient to assess the effects on health outcomes because of limited
number or power of studies, important flaws in their design or conduct, gaps in the chain
of evidence, or lack of information on important health outcomes.

Study offers women more complete picture of HRT risks,

benefits
Detailed results of the "estrogen-alone" study within the Women's Health Initiative
(WHI), which was terminated in early March 2004, are providing some of the first
answers to questions about the efficacy of estrogen alone to prevent chronic disease in
healthy, postmenopausal women who have had a hysterectomy. WHI researchers,
including investigators at Brigham and Women's Hospital (BWH), have shown that after
6.8 years of study on more than 10,000 women nationwide, estrogen-alone hormone
replacement therapy (HRT) in postmenopausal women increased the risk of stroke,
reduced the risk of hip fracture, and had minimal effect on the risk of heart disease and
breast cancer. In addition, the research suggests that women who start estrogen earlier in
life may receive more heart health benefits than those who start later in life. These
findings are published in the April 14 issue of the Journal of the American Medical
Association.

According to JoAnn Manson, chief of preventive medicine and principal investigator of

the WHI at BWH, "These results suggest that the risks and benefits of estrogen therapy
are fairly balanced, but these hormones should not be taken to prevent cardiovascular
disease. More research is needed to understand if the benefits outweigh the risks in
younger women beginning estrogen shortly after menopause. Estrogen therapy still has a
role in the short-term treatment of menopausal symptoms, but the lowest dose should be
used for the shortest duration of time possible."

The estrogen-alone study involved 10,739 women ages 50 to 79 years who were studied
for 6.8 years. Study participants were randomly assigned either a daily dose of hormone
replacement therapy (HRT) - 0.625 mg/day conjugated equine estrogen (CEE) - or a
placebo. The study's main goal was to determine the impact estrogen alone has on
coronary heart disease risk, but like the "estrogen plus progestin" study, which was
stopped in 2002, an increased risk of stroke was found. Specific findings related to
estrogen-alone HRT include:

 Coronary heart disease risk did not increase or decrease

 Stroke risk increased 39 percent with the most pronounced increase occurring among
women who were 60 years old and older
 Breast cancer risk decreased by 23 percent, which was not statistically significant and
indicates that further study is necessary to determine estrogen impact on breast health
 Pulmonary embolism risk increased 34 percent
 Hip fractures decreased by 39 percent
 Evidence for a small increase in dementia and mild cognitive impairment were
observed in women age 65 and older. A separate research report will be issued at a later
date on these findings.

According to Manson, who is also a professor of medicine at Harvard Medical School,

"In the early 1990s, an estimated 15 million women were taking HRT without clear
information about the health benefits or risks associated with its use. These study results
will help women and their clinicians make more informed choices about the use of
estrogen therapy."

The Women's Health Initiative involves more than 161,000 women who are either
participating in a set of clinical trials to test preventive measures for heart disease,
fractures, breast and colorectal cancer, or in a large observational study. In addition to the
trials of estrogen alone and estrogen plus progestin, other WHI trials are studying a low-
fat diet pattern and calcium/Vitamin D supplementation. These trials are continuing.