More on oestrogen and breast cancer.
My medical career has always been guided by what is best and safest for my patients. I read extensively and keep very up to date with the latest information regarding health, and hormones in particular. Some of it can be very technical, and a knowledge of biochemistry, statistics and epidemiology is necessary. I do not expect the average person to be Au fait with these subjects.
I began using natural progesterone before it became popular, and now it is accepted as the safest form of progesterone. I used hormones as troches (transdermal), when most form of hormones were given as a pill. Now transdermal is recognized as the safest form of giving hormones.
I have written this blog for over 10 years, so that I can share my knowledge with you, my readers, so that you may have a credible source of information about the things that effect you.
In a previous blog, I mentioned that there are 3 oestrogens women produce: Oestrone (E1), Oestradiol(E2) and Oestriol(E3). There is actually a 4th oestrogen, estetrol (E4), which is produced in large amounts in pregnant women – which could be one of the reasons breast cancer is very rare in pregnancy, and the more pregnancies women have, the lower the risk of breast cancer.
Biest, the oestrogen used in troches, is made up of 80% Oestriol(E3), and 20% Oestradiol (E2). As you can see if you wade through the research I have published on my blogs recently, E3 counteracts any negative effects on the breasts that E2 might have. This is probably part of the reason that my statistics for the amount of breast cancer my patients get is below the national average. Those of you who are interested, and that includes the many doctors who subscribe to my blog, can wade through all the details below, and to follow. Otherwise, just take it as read.
Estriol: Its Weakness is Its Strength
August 2008
By Olivia A.M. Franks, ND and Jonathan V. Wright, MD
|
Estriol, an estrogen that has virtually been ignored by the mainstream medical community, is one
of the three principal estrogens produced by the body. Estriol was originally thought to have
little significance due to its weak estrogenic activity when compared with estrone and
estradiol. Nonetheless, research has found that its weakness may very well be its strength.
Studies suggest that when the lower-potency estrogen, estriol, is administered topically, it does
not increase the risk of hormone-dependent cancers of the breast or endometrium (uterine
lining).1-3 However, having weaker estrogenic effects
does not mean that estriol has none of the benefits that come with more potent estrogens.
Studies suggest that estriol reduces symptoms of menopause, such as hot flashes and vaginal
dryness, but with a better safety profile compared with more potent estrogens.1,4,5 This makes estriol a better choice for bioidentical
hormone-replacement treatment regimes.
That is not all this ‘weak’ hormone is good for! Research suggests that estriol has benefits for
bone density, heart health, multiple sclerosis, and postmenopausal urinary tract health.6-12 In this article, we will review the attributes of
this ‘weaker’ estrogen, and why this estrogen is currently in the news.
What you need to know
The body naturally makes three estrogen hormones—estradiol, estrone, and
estriol. Since estriol possesses the weakest estrogenic effects of the
three, it has been largely overlooked by the medical community.
Many studies show that estriol offers a wealth of potential health
benefits—without the dangers that sometimes accompany higher-potency
estrogens and synthetic or horse-derived hormones.
Studies suggest that estriol helps relieve menopausal symptoms while
benefitting bone and urinary tract health. Estriol may also help improve
cardiovascular risk factors and even shows promise in reducing the brain
lesions of multiple sclerosis.
The most reliable way to measure estriol levels is through 24-hour urine
collection.
Despite abundant evidence to the contrary, the FDA has recently claimed
that estriol is not safe. You can act now to help preserve consumers’
access to bioidentical hormones such as estriol by visiting
http://www.anh-usa.org/home-coalition-redirect/.
Fear of cancer prevents many women from restoring youthful hormone
levels. When applied through the topical (transdermal) route, estriol is
not associated with increased cancer risk. Other methods women can use
to prevent hormone-related cancers include consuming abundant vitamin D,
cruciferous vegetables, soy, D-glucarate, and lignans, while minimizing
meat and high-fat dairy intake.
Estriol and Hormone Replacement Therapy
If you are on hormone-replacement therapy (HRT) and have never heard of estriol, you might be
wondering why not? Before the 1970s, estriol was thought to have significance only during
pregnancy. Levels of estriol are elevated in pregnancy up to 1,000 times compared with normal
non-pregnant levels.
In the 1960s, we saw the beginning of hormone-replacement therapy with patented equine estrogens
such as Premarin® and synthetic progestins as found in Provera®. By the 1990s, one-third of
menopausal women were taking Premarin®. Research uncovered the increased incidence of breast
cancer, increased risk of blood clotting, and increased cardiovascular risk associated with the
use of these horse-derived and synthetic hormones (used in combination in the patented
medication Prempro®).13 The medical community began to
wonder if using hormones from pregnant horses was such a good idea. In an effort to find a safer
alternative, many patients and practitioners began looking into ‘natural’ hormone-replacement
treatment using bioidentical hormones, which are identical to those produced naturally within
the body. Bioidentical-hormone replacement was pioneered in the 1980s as a treatment for
menopause by Dr. Jonathan Wright in Washington state.
Interest in estriol increased as it was discovered that estriol was safer than horse-derived and
synthetic hormones in relation to cardiovascular health and potentially cancer risk.
Unfortunately, many doctors have not adopted its use, and many bioidentical hormone-replacement
regimes use only estradiol, a more potent estrogen with increased associated risks.
The benefits of estriol may, in part, be explained by the mixed pro-estrogenic and
anti-estrogenic effects of this interesting estrogen hormone. Scientists Melamed et al.
investigated the mixture of stimulating and non-stimulating effects posed by estriol upon
estrogen receptors. When estriol is given together with estradiol, the estradiol-specific
stimulation to cells is decreased. This little-appreciated scientific fact helps to explain how
estriol can reduce pro-carcinogenic effects of more powerful estrogens like estradiol. However,
when estriol is given alone over a long period of time, it can produce a more complete
pro-estrogenic effect, explaining why symptom relief is achieved when menopausal women take
estriol.2 Experimental studies suggest that both
estriol and tamoxifen (a synthetic anti-estrogen) have protective effects against
radiation-induced cancer of the breast.14
Safety Concerns
Most of the research cited in this article used oral estrogen as the route of
administration. However, for enhanced safety, topical estriol would be a better
choice. Several studies have shown that transdermal estrogen confers less health
risk as a route of administration than oral estrogen.3,21-25 Clinical experience of many
doctors over the past 20-30 years suggests that transdermal estrogen is also
more effective for some women. This is largely thought to be due to the
‘first-pass effect’—meaning that orally ingested drugs are often first
metabolized in the liver, before having any activity in the body. Orally
ingested estrogen hormones are among these drugs that are first metabolized in
the liver before exerting their effects in the body. Physicians experienced in
hormone replacement often observe that women treated with oral estrogens show
high levels of estrogen metabolites in 24-hour urine specimens, suggesting that
most of the orally ingested hormones are being excreted.
In addition, several studies suggest that bioidentical estrogen has less health
risk when given with low doses of bioidentical progesterone.26,27
In a prospective study funded by the US Army and performed at the Public Health Institute,
Berkeley, California, researchers compared estriol levels during pregnancy with breast cancer
incidence 40 years later. Results revealed that of the 15,000 women entered in the study, those
with the highest levels of estriol relative to other estrogens during pregnancy had the lowest
cancer risk. In other words, as the relative level of estriol increased during pregnancy, risk
of breast cancer decreased 40 years later. In fact, women with the highest level of estriol
during pregnancy had 58% lower risk for breast cancer compared with women who had the lowest
serum estriol levels. The authors also noted that Asian and Hispanic women had higher estriol
levels compared with other racial groups. Interestingly, Asian and Hispanic women have the
lowest breast cancer rates. The authors concluded, “If confirmed, these results could lead
to breast cancer prevention or treatment regimens that seek to block estradiol estrogen action
using estriol, similar to treatment based on the synthetic anti-estrogen tamoxifen.”15
In another study, Takahashi et al. studied the safety of estriol treatment for menopausal
symptoms. Fifty-three women with either surgically induced or natural menopause were given 2 mg
of oral estriol/day for 12 months. Endometrial and breast assessments done with endometrial
biopsy and breast ultrasound, respectively, found normal results in all women. The authors
concluded that over a 12-month period, “estriol appeared to be safe and effective in
relieving symptoms of menopausal women.”1
In one investigation, 52 postmenopausal women were given 2 mg, 4 mg, 6 mg, or 8 mg/day of oral
estriol for six months. In all patients, vasomotor symptoms of menopause (such as hot flashes)
were decreased. The most improvement was experienced by women taking the highest dose of 8 mg.
There were no signs of endometrial hyperplasia confirmed by endometrial biopsy over the
six-month treatment period. Mammograms were obtained on six of the patients who had mammary
hyperplasia at the study’s outset, and no further changes were seen.8
Although the oral route of administration of estriol appears relatively safe over the short-term,
the transdermal route is preferred for long-term use. For example, Weiderpass et al. found an
increased risk of endometrial atypical hyperplasia and endometrial cancer with oral use of
estriol, but not with transdermal estriol over at least a five-year period. Compared with no use
of estriol, those who took oral estriol for at least five years had a significantly greater
risk, compared with individuals who did not take any estriol. Women using topical estriol for at
least five years did not have any increased risk.3 As
you will read in the “Safety” box, several studies suggest that the use of topical
natural progesterone cream may further reduce the risk to the endometrium.16-18
Henry Lemon, MD, a women’s cancer specialist, took this research one step further and developed
the concept of the estrogen quotient—the ratio of estriol to the sum of estradiol and estrone
(estriol/estrone+estradiol). By looking at this ratio of ‘good’ estrogen to ‘bad’ estrogen, a
physician can evaluate breast cancer risk and prescribe estrogen replacement better tailored to
the individual to reduce cancer risk. The estrogen quotient can be evaluated from a 24-hour
urine hormone panel.19,20
Estriol Reduces Markers of Cardiovascular Risk
Growing evidence suggests that estriol may offer protective benefits for the cardiovascular
system. For instance, Takahashi et al. found that some women with natural menopause given 2
mg/day oral estriol for 12 months had a significant decrease in both systolic and diastolic
blood pressure.1
Another study compared the use of oral estriol at a dose of 2 mg/day for 10 months in 20
postmenopausal and 29 elderly women. Some of the elderly women had decreases in total
cholesterol and triglycerides and an increase in beneficial high-density lipoprotein (HDL).7
Estriol Improves Bone Mineral Status in Women With Osteoporosis
A Japanese study involving 75 postmenopausal women found that after 50 weeks of treatment with 2
mg/day of oral estriol cyclically and 800 mg/day of calcium lactate, women had an increase in
bone mineral density, a decrease in menopausal symptoms, and no increased risk of endometrial
hyperplasia (tissue overgrowth that may precede cancer).6
Similarly, Nishibe et al. investigated treatment of postmenopausal and elderly women with 2
mg/day of oral estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate
alone. The bone mineral density significantly increased in women who received estriol, whereas
the women who did not take estriol experienced a decrease in bone mineral density.7
Estriol Reduces Brain Lesions of Multiple Sclerosis
The high levels of estriol during pregnancy have been known to alleviate some autoimmune
conditions due to its ability to shift immune response.9 For instance, Sicotte et al. at the Reed Neurological
Research Center in Los Angeles investigated the effects of pregnancy-level doses of estriol (8
mg/day) in non-pregnant women with multiple sclerosis (MS). Cerebral MRI images showed a
significant reduction of gadolinium-enhancing cerebral lesions from multiple sclerosis. These
lesions increased when treatment stopped and decreased when treatment was restarted.28 Gadolinium is a contrast agent used in certain MRI
studies; gadolinium-enhancing lesions are associated with an increased inflammatory response
marking disease progression in patients with MS. Lowered amount of these lesions seen on MRI
with gadolinium contrast would equate to a decrease in disease progression.
This effect may also apply to men with autoimmune conditions. Another team of researchers from
the Reed Neurological Research Center in Los Angeles found that estriol treatment ameliorates
experimental autoimmune encephalomyelitis (EAE) in males, compared with placebo treatment.29 EAE is an experimental demyelinating inflammatory
disease that shares numerous characteristics with MS. Estriol treatment also resulted in a
decrease of proinflammatory immune markers. This is very promising news for patients and their
doctors who are struggling to treat challenging neurological conditions associated with
inflammation.
Estriol Protects Urinary Health in Postmenopausal Women
Postmenopausal women who suffer from incontinence or recurrent urinary tract infections will be
pleased to know that estriol offers benefit in the context of these troublesome conditions. In a
prospective, randomized, placebo-controlled study, 88 women were given 2 mg intravaginal estriol
suppositories (once daily for two weeks, then twice weekly for six months) or placebo. Of the
women in the estriol group, 68% reported improvement in symptoms of incontinence. In addition,
measurements of mean maximal urethral pressure and mean urethral closure pressure were
significantly improved.10
In another randomized, double-blind, placebo-controlled trial, women with recurrent urinary tract
infections (UTI) were given either intravaginal estriol cream (containing 0.5 mg estriol, once
daily for two weeks, then twice weekly for eight months) or placebo. The incidence of urinary
tract infection was dramatically reduced in the estriol group compared with placebo (0.5 versus
5.9 episodes per year).11
Measurement of Estriol
Hormones produced by the body are secreted in pulses, while hormones taken transdermally or
orally will initially be very high and slowly decline over the course of the day. This
scientific reality makes testing for estriol at a single point in time—as would be the case for
saliva or serum testing—very inaccurate. There are too many variables: When did your body last
put out a pulse of the hormone under investigation? When did you take your hormone-replacement
therapy? Estriol in particular does not last very long in the blood. In fact, the half-life of
estriol has been shown to be between 3.6 and 64 minutes.30
The more accurate way to assess estriol is by collecting what is excreted during a 24-hour urine
collection. This form of testing ensures that we have an accurate value that is not affected by
the fluctuations of the day, because we are measuring 24 hours’ worth of hormone production.
Estriol in the News
Recently, the FDA made claims that estriol—a hormone naturally produced by women’s bodies—is not
safe, even though the FDA did admit at a press conference that no adverse effects from estriol
have ever been reported. After reading about the benefits of estriol that research has
uncovered, it is hard to understand why the FDA would want to take this more protective estrogen
off the market and out of reach of the many thousands of women seeking relief from menopausal
and postmenopausal symptoms.
This recent attack on estriol also includes all bioidentical hormones produced by compounding
pharmacies. Why are these substances such a threat? This is not the first time the FDA has made
attacks on unpatented natural substances. Bioidentical and therefore unpatentable hormones are a
threat to the income of big drug companies. The fees paid by these big drug companies are a
large portion of FDA income. Would you not say that there is a conflict of interest here? Why
would any woman want to take horse estrogen or chemically imprecise, yet patentable estrogen
rather than estrogen that is identical to that produced by women’s own bodies? This is even more
questionable in the light of all the negative research showing increased health risks from these
FDA-approved substances. And is it not the job of the FDA to make sure that women get safe and
effective medicine? It seems the FDA has largely lost sight of its original goals. For more
information on this and to take action, please visit the HOME (Hands Off My Estrogen!) Coalition
website at http://www.homecoalition.org.
Summary
Estriol, once thought of as insignificant and weak, actually has protective effects against
stronger estrogens. For this reason, it is a relatively safer choice for bioidentical
hormone-replacement therapy. We have learned that safety is also increased by using topical
administration instead of oral administration, and by balancing estrogen with progesterone.
Estriol has benefits beyond treating typical postmenopausal symptoms. Estriol offers potential
benefit for people with MS, postmenopausal women prone to urinary tract infection or
incontinence, and menopausal/ postmenopausal women with osteoporosis. It would be a great shame
to lose this wonderful tool before it was ever fully utilized.
If you have any questions on the scientific content of this article, please call a Life Extension
Health Advisor at 1-800-226-2370.
Is Fear of Cancer a
Reason to Be Deprived of Hormones?
As women enter their menopausal years, they face a difficult decision. The body’s
natural production of estrogen, progesterone, dehydroepiandrosterone, and other
critical hormones needed to maintain health and vigor rapidly declines.31,32 While individual effects of
menopause vary widely, most women suffer because their glands no longer produce
the hormones needed to regulate critical physiological processes. Depression,
irritability, and short-term memory lapses are common menopausal complaints,
along with hot flashes, night sweats, and insomnia.31
Concern about cancer is the primary reason why women do not restore their
hormones to more youthful levels. Like much of what we eat, estrogen and
testosterone affect cell proliferation. Does that mean we should shrivel up,
degenerate, and die from these sex hormone deficiencies we all face as a part of
“normal” aging?
Based on the data showing how people may reduce their rate of cancer and
favorably affect estrogen metabolism in a way that points to cancer prevention
(by consuming lots of cruciferous vegetables, for example), it is difficult to
buy into the argument that natural sex hormones should only be enjoyed by the
young.
Large human population studies show huge reductions in cancer risk and specific
protective mechanisms against estrogen’s negative pathways when vitamin D,32-36 cruciferous vegetables (a source of
indole-3-carbinol, or I3C),37-42
soy,43-48 D-glucarate,49-52 and lignans53-55 are consumed. Dramatic cancer rate
reductions also occur when red meat, high-fat dairy, and other deleterious foods
are reduced or eliminated from the diet.43,55-58
Misconceptions generated by conflicting studies and media hype have created an
environment in which aging people suffer the agonies and shortened life spans
caused by sex hormone imbalances, yet do nothing to correct this due to fear of
cancer. When one looks at what the real cancer risk factors are, it would appear
that altering one’s lifestyle at any age would result in significant reductions
in malignant disease, including those who properly restore their natural hormone
balance to reflect a more youthful range.
The Real Cause of Breast Cancer
To enable members to fully understand the carcinogenic effects of aging, we have
reprinted on this page a chart showing women’s breast cancer risk by age.59 A quick look at this chart clearly
documents that aging is the primary cause of breast cancer. The good news is
that the gene expression changes involved in the development of breast cancer
can be favorably altered by taking low-cost nutrients like vitamin
D60 in the dose of 1,000 IU to 10,000 IU/day, based on individual
need.
Risk of Developing
Breast Cancer by Age59
By age 25: 1 in 19,608 By age 30: 1 in 2,525 By age 40: 1 in 217 By age 45: 1 in 93 By age 50: 1 in 50 By age 55: 1 in 33 By age 60: 1 in 24 By age 65: 1 in 17 By age 70: 1 in 14 By age 75: 1 in 11 By age 80: 1 in 10 By age 85: 1 in 9 During the younger years, when breast cancer is virtually non-existent, we enjoy high levels of our sex hormones (estrogen, progesterone, dehydroepiandrosterone, and testosterone). As we age and hormone levels decline, breast cancer risks increase. The reason “aging” causes cancer is that the genes in our cells that regulate cell proliferation become increasingly mutated. The accumulation of mutations to our cells’ regulatory genes is the underlying cause of cancer.61 It is encouraging to know that there are low-cost nutrients that favorably restore healthy gene function and reduce our risk of cancer in the process. A newly published study cites evidence that vitamin D can exert its cancer-preventing effect by counteracting the growth-promoting effect of estrogens.62 Vitamin D also exerts its cancer-preventive influence by helping to control cell differentiation and inducing normal programmed cell disposal (apoptosis).62 Based on the enormity of these data, it would appear that aging humans can restore many of the hormones they need to sustain life—without encountering adverse effects. Having said this, we have to remind readers that there are still no long-term safety data on the safety of even weak exogenously administered estrogens like estriol. Based on the totality of evidence that exists to date, it would appear that the estriol confers many benefits, while definitive protective measures against breast and other cancers can easily be incorporated into a healthy lifestyle. —William Faloon |
| References |
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Dr Colin Holloway 