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ESTROGEN -- Fails the Heart Test
Following is an article from Life Extension Magazine regarding hormone replacement
therapy.
Life Extension Magazine June 1999 by Terri Mitchell
The bubble has burst for estrogen and heart disease. Two
studies involving thousands of women show that synthetic hormone replacement increases the
risk of heart attack in postmenopausal women.
Researchers involved in two studies have warned that women should not take synthetic
hormones to prevent heart attacks. Almost all of the women in both studies were taking
Premarin, which casts further doubt on this best-selling
drug. Coupled with its history of causing fatal blood clots and breast cancer, this new
finding should be a wake-up call to women currently taking Premarin. Safer alternatives
are readily available.
Heart disease is a serious problem. It kills more women over the age of 60 than any other
disease. At half a million deaths, it dwarfs breast cancer which will claim about 43,000
lives this year. (Between ages 40 and 60, however, cancer is the biggest killer.)
Because the incidence of heart disease rises sharply in women after menopause,
researchers have thought that female hormones are protective. They theorized that this
protection could be extended with synthetic replacement. These ideas were
strengthened when observational studies showed that women taking estrogen and
progesterone had a lower rate of heart disease. In 1995, the Postmenopausal
Estrogen/Progestin Intervention trial (PEPI) established that estrogen replacement has a
positive effect on lipids and clotting factors. Although it was questionable whether this
would translate into fewer heart attacks, it was all some doctors needed to begin
prescribing synthetic
hormones for heart disease. The warnings of Jacques Rossouw (NIH) and others went unheeded
in the belief that synthetic estrogen was the answer to heart attacks in postmenopausal
women.
In 1994, a large-scale study was begun at 20 medical centers across the U.S. Called the
Heart and Estrogen/Progestin Replacement Study (HERS), it was the second largest study of
its type ever attempted. Funded by pharmaceutical
giant Wyeth-Ayerst, every expectation was that HERS would prove that synthetic hormones
would prevent heart attacks in postmenopausal women. Two thousand women with heart disease
were put on "Prempro," a combination of
Premarin and medroxyprogesterone acetate (a synthetic progestin). By 1998, the results
were in: Prempro substantially increased heart attacks the first year and had no effect on
heart attacks in subsequent years. Blood clots were three times higher in the group that
took Prempro, and gallbladder disease was also increased.
It won't be easy to explain this study as a fluke: researchers from Duke University have
reported the same findings. In that study, 37% of women who began taking synthetic hormone
replacement after their first heart attack were hospitalized for heart problems compared
to 17% of women who did not take the drugs. Most of the women in the study were on
Premarin. In 1997, it was reported in the British Medical Journal that an analysis of 22
studies shows that synthetic hormones do not prevent heart attacks.
Another study concluded that synthetic hormones increase the risk of a blood clot
four-fold. Although the risk of blood clots appears to decline after the first year of
use, and cardiovascular benefits-if any-may increase after years of use, the overall
consensus is that women should not take synthetic hormones for heart attack prevention.
How could something so promising turn out so negatively? Scientists are scrambling for an
explanation. Maybe it would work in healthy women, they suggested. Perhaps the study was
too short. (Prempro tended to show a better effect after four or five years). The most
common argument was that the synthetic progestin cancelled out the good effects of
synthetic estrogen.
Studies show that adding progesterone to estrogen replacement dampens the lipid-lowering
effects of the estrogen. However, this argument doesn't hold up because although synthetic
progesterone does reverse some of the beneficial effects of estrogen on lipids, it doesn't
completely obliterate them. This has been confirmed in studies that show no difference in
heart attack incidence when progestin is added to synthetic estrogen. Also, it is unlikely
that its lipid effects account for estrogen's heart benefits. At least four other
mechanisms have been proposed. They include its effects on
elasticity of blood vessels, its antioxidant action, its ability to enhance vasodilation,
and its effects on clotting factors. Clearly, another explanation for the negative studies
has to be found.
One of the issues that has been consistently overlooked in estrogen/heart studies is the
type of hormones used. Studies indicate that different brands of hormones may have
different effects. The type of estrogen used in the HERS study was Premarin, which had
seemed to reduce the incidence of heart attack
in a study known as the Nurse's Health Study. (However, that study has been criticized for
not taking into account certain factors that could have been responsible for the lower
incidence of heart problems, including access to healthcare. Since the nurses were taking
homocysteine-lowering supplements, it is likely that they, too, played a role in the lower
rate of heart attacks. And, unfortunately, even if the Nurse's Health Study were to still
show benefit after statistical corrections, the women who took Premarin would still lose
because it was discovered that they had a significantly higher risk of breast cancer.)
Premarin is the brand of synthetic estrogen taken by most of the women in the two recent
studies. Known as "conjugated equine estrogens," it is made from horse urine.
This type of estrogen has performed poorly in previous heart disease studies, including
one on men that had to be stopped because of the increased number of heart attacks at the
dose of 5 mg/day, and greater mortality from other causes at 2.5 mg/day. Its manufacturer,
Wyeth-Ayerst, has been accused of animal cruelty in the production of the drug, which
involves collecting the urine of confined horses. (This type of practice
dates back to the 15th century when yellow paint was made from cow's urine.In order to
create the salts necessary for the paint, people would feed cows exclusively on mango
leaves, which killed them prematurely. The British government finally outlawed it at the
turn of the century. Other types of synthetic estrogens do not involve animals, and may
have the benefits researchers hoped to find in estrogen.
The "patch" type synthetic estrogens have made a good showing in several studies
that measured lipids. And transdermal estrogen has produced good one-year results in an
Italian study-no heart attacks or blood clots. Unlike horse urine estrogen, these types of
replacement therapies contain 17b-estradiol, a synthetic form of estrogen made from
plants. 17b-estradiol improves heart function, lowers cholesterol and elevates HDL, the
"good cholesterol." 17b-estradiol estrogens also have a more favorable effect on
blood sugar than Premarin. This is important, as disruptions in glucose
tolerance have been linked to heart disease. Time will tell whether the plant-derived
forms of synthetic estrogen will reduce heart attack risk.
While data is accumulating on synthetic estrogens, natural estrogens are safe and
available. Soybeans and other plants appear to protect against heart disease without the
side effects of synthetic estrogens, which carry with them a four-fold increased risk of
blood clots and a 30% increased risk of breast cancer. Instead of creating
life-threatening conditions,
phytoestrogens and other plant substances appear to protect against them.
Phytoestrogens are part of a group of substances known as phytochemicals-beneficial
substances from plants. One of the ways phytochemicals may protect against heart
disease is by scavenging free radicals. Free radicals oxidize fat. People with heart
disease have abnormally high amounts of oxidized fat in their arteries. The antioxidant
protection of phytochemicals also decreases DNA damage to mitochondria. This is important
because mitochondria are the power source for the heart. When they break down, heart
muscle suffers. Phytochemicals are broken down into categories.
Flavonoids are a type of phytochemical that has been shown
to lower the risk of heart attack, as well as lower mortality from heart disease. This
protection is above and beyond that provided by antioxidants Cand E. Antioxidant reserves
are low after a heart attack, and should be replaced. A study in rats shows that vitamin E
supplements improve cardiac function after a heart attack. So does curcumin, a
phytochemical from a root similar to ginger. Lycopene, a carotenoid that gives tomatoes
their red color, is also heart-protective.
There are over 4,000 flavonoids. They are found in tea, grapes, onions citrus fruit, and
many other plant products. Two of them, quercetin (onions, red wine, broccoli) and
catechin (tea) greatly reduce free radicals created by diets high in poly and
monounsaturated fats. The American diet is rich in n-6 polyunsaturated fat, present in
oils such as corn and safflower. The latter fat type, when combined with a lack of
antioxidant vitamin E, has adverse effects on arteries. In Israel, where n-6
polyunsaturated fat in the diet is even higher than in the U.S., there is high incidence
of cardiovascular disease and cancer in women.
Quercetin and catechins can reverse this effect by
conserving vitamin E. Tea contains phytochemicals known as polyphenols that protect
against heart disease. In a study from Harvard Medical School, drinking one or more cups
of tea a day slashed heart attack risk in half.
It has been demonstrated that the antioxidant power of single phytochemicals such as equol
(from soy) and coumestrol (from clover and alfalfa sprouts) is as strong, or stronger,
than 17b-estradiol. Several plant substances, including a flavonoid in apples, appear to
have both the estrogenic and the antioxidant power of 17b-estradiol. Apples were a main
source of flavonoids in two studies showing that flavonoids reduce heart disease in
humans. The heart-protective effects of flavonoids are apparent in a study on doxorubicin
("dox"). Dox is used as chemotherapy in breast cancer, but it's
toxic to the heart. Researchers in the Netherlands have shown that flavonoids protect mice
from dox cardiotoxicity almost completely.
The most well-studied phytoestrogens are from soy, genistein and daidzein. Genistein
possesses strong antioxidant action, and lowers cholesterol. The best study to date on soy
and heart disease was done on monkeys. It found that soy greatly reduced atherosclerosis.
Soy also decreased lipid peroxidation, improved insulin sensitivity, and improved lipid
profiles.
When genistein and daidzein were removed from the soy, its beneficial effects were greatly
reduced. Adding 17b-estradiol to the soy diet caused weight reduction and reduced stomach
fat.
Phytoestrogens produce effects similar to what drugs offer. Dozens of studies document
genistein's calcium channel blocking action. Genistein also increases the sensitivity of
the heart to beta-blockers, inhibits blood clotting factors, and helps blood vessels
relax. We can only guess at what other benefits soy has that have not yet been discovered.
Synthetic estrogens have been promoted for maintaining strong bones. Their long-term
effects are not known, however. Soy, on the other hand, has a thousand-year track record
with proven benefits for bone. In a study from Japan, genistein improved bone strength and
density, while daidzin prevented bone loss. Daidzin also prevented atrophy of the uterus
caused by removal of the ovaries. Soy is so effective at preserving bone that it rivals
calorie restriction in its effects. It has been proven that the bone loss associated with
meat-based diets can be substantially reversed with soy. Some women
have expressed concern that phytoestrogens might increase their risk of breast cancer just
as synthetic ones do. However, the opposite appears to be true. According to Dr. Richard
St. Clair of Wake Forest University, phytoestrogens decrease, rather than increase, the
proliferation of breast and uterine cells. Dozens of studies show that phytoestrogens
actually inhibit breast cancer cell growth. St. Clair also points out that in Asia, where
soy consumption is high, breast cancer incidence is much lower than in the U.S. where soy
consumption is low.
Phytoestrogens provide estrogenic benefits without the dangerous side effects of synthetic
hormones. Coupled with the lack of benefit for heart disease, the side effects of Premarin
make it a poor choice for hormone replacement. Until more is known about the 17b-estradiol
synthetic estrogens, the best choice for heart health is a combination of flavonoids,
phytoestrogens and other natural factors proven to have a beneficial effect.
While eating a diet high in fruits and vegetables may theoretically provide enough
flavonoids and phytoestrogen for heart protection, the vast majority of women do not
consistently "eat right" day-in and day-out. Supplements ensure that beneficial
heart factors are consistently available to the body. Postmenopausal women who exercise,
eat a good diet and take supplements should feel secure that they're doing everything
possible to forego America's number one killer, heart disease-without adverse side
effects.
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