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Experience the Difference of Natural Bioidentical Hormones

“New Analysis Uncovers Safer, More Effective Way Of Delivering Hormone Replacement Therapy For Postmenopausal Women”
Comprehensive review of clinical literature reveals bioidentical hormones provide improved symptomatic and cardiovascular benefits over synthetic HRT while reducing the risk of breast cancer
(click for abstract)

Experience the Difference of Natural Bio-identical Hormones

We specialize in natural prescription bio-identical hormone replacement. Dr. Holtorf has been using and preaching the superiority and safety of natural hormones verses synthetic for many years (long before the Women’s Health Initiative Study). There are many doctors that now claim to specialize in natural hormones but our expert knowledge and experience can make the difference between feeling great and so so.

Get Off Premarin,
Provera, Prempro and
other Synthetic Hormones

And get on to the safe and natural pharmaceutical hormones.

Kent Holtorf, M.D. can help you actually obtain the health benefits you have been striving for without compromising your health with the side effects of the synthetic hormones you have heard about on the news.

Side Effects of Synthetic Hormones:

  • Increased Risk of Stroke & Heart Attack
  • Increased Risk of Certain Cancers
  • Negates Positive Effects of other Hormones
  • Weight Gain
  • Depression
  • Fatigue
  • Non-effective

Breast Cancer and BHRT
Aging and Estrogen Levels
Review of Suzanne Somers Book, "The Sexy Years"
Is Hormone Replacement Right for You?

  (Bioidentical vs. Synthetic)
WHI Study Confusion
Scientific Review of Natural vs. Synthetic Hormones







Breast Cancer and BHRT

Bioidentical hormones are again shown be superior to synthetic hormones, and this is continuing proof that bioidentical hormones are not associated with breast cancer while synthetic versions significantly increase the risk of breast cancer.

Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Fournier A, Berrino F, Clavel-Chapelon F. Breast Cancer Research and Treatment 2007

One of the largest studies to date comparing the risk of breast cancer with the use of natural bioidentical hormones and synthetic hormone replacement therapy demonstrates that the natural hormones have significantly less associated risk of breast cancer. This study published a 2007 issue of Breast Cancer Research reported the association between various forms of HRT and the incidence of breast cancer in over 80,000 postmenopausal women who were followed for over 8 postmenopausal years. This study found that, compared to women who never used any hormone replacement therapy, women who used estrogen only (different preparations analyzed together) had an increased risk of breast cancer that was 1.29 times those who never used estrogen. If a synthetic progestin was used in combination with estrogen, there was a significant increase in the risk of breast cancer compared to those on the estrogen only that was 1.69 times the risk of those who never used estrogen.

If, however, a woman used natural progesterone in combination with estrogen, the increased risk of breast cancer was eliminated, having no increase risk o f breast cancer as compared to those who never used estrogen. In addition, estriol containing products was found to have a further protective effect against breast cancer, resulting in a lower risk of breast cancer than even those who did not use any hormone replacement.

This study adds to the mass of previous medical literature that demonstrates the superior safety of bioidentical hormone replacement as compared to synthetic hormones.







“New Analysis Uncovers Safer, More Effective Way Of Delivering Hormone Replacement Therapy For Postmenopausal Women”
Comprehensive review of clinical literature reveals bioidentical hormones provide improved symptomatic and cardiovascular benefits over synthetic HRT while reducing the risk of breast cancer

The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy?

By Kent Holtorf, MD
Published in © Postgraduate Medicine, Volume 121, Issue 1, January 2009, ISN – 0032-5481,

Abstract

Background: The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. Objective: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease.

Methods: Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected.

Results: Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone. Conclusion: Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly. (full article available at http://www.postgradmed.com)




Aging and Estrogen Levels



Women with Low estrogen look significantly older than women the same age with more optimal levels of estrogen
THE LANCET
  • Low estrogen levels are associated with accelerated aging, including the loss of collagen and moisture content of skin as well increased facial wrinkling. Conversely, natural estrogen replacement has been shown to improve collagen levels and moisture content of the skin and reduce wrinkles.
    .
  • A panel of independent reviewers estimated the ages of 100 women on their first office visit to a gynecology practice. The women’s estimated age was then compared to their real age and the level of estrogen.
    .
  • The women ranged 35-55 and it was as found that women with low estrogen levels looked significantly older than their age and those with more optimal levels looked much younger than their age.
    .
  • There was a direct correlation with the level of estrogen and looking older or younger than one’s real age. Those with the lowest level of estrogen looked 8 years older than their age and those with the most optimal levels looked 8 years younger than their age (16 year differential).
    .
  • The authors state, “The age of women with low estradiol serum concentrations was systematically overestimated; with increasing serum estrogen levels the reverse was the case. Women with high estrogen concentrations looked younger, women with low estradiol concentrations older than they really were. The discrepancy between estimated and real age could be as high as 8 years in either direction [16 year differential]. These data suggest that serum estrogen concentrations have a pronounced impact on the estimation of age.”

aging_chart.jpg




Review of Suzanne Somers Book, “The Sexy Years”



Review of “The Sexy Years”
by Kent Holtorf, M.D.
  • Overall an excellent book that has brought needed attention to bioidentical hormones
  • While the method described in the book is far superior to commonly used synthetic HRT, it is not the most optimal regimen currently available.
  • Following are some important points that need to be taken into account when deciding on treatment after reading the book:

1. The recommendation that oral estradiol be used.

  • Oral estradiol is superior to Premarin and other synthetic oral estrogens, but when given orally it also increases the risk of stroke, heart attack and DVT when compared to transdermal (gel) estrogen.
  • When any estrogen is given orally, it goes through the liver and stimulates binding proteins for thyroid, testosterone, adrenal hormones and growth hormone, lowering these hormones with potentially detrimental effects. This does not occur with transdermal preparations.
  • Oral estradiol will increase inflammation, including CRP, which increased the risk of heart disease. This does not occur with transdermal preparations.
  • When oral estrogen is given, it is first metabolized by the liver (called 1st pass metabolism) which breakdowns the estrogen to unwanted metabolites (you don’t get what you give)
  • Oral estrogen increases insulin resistance while transderamal does not.

2. Dr. Schwarzbein does not mention or use estriol.

  • She makes the point that women just have to live with the increased risk of breast cancer without apparently knowing of the anti-breast cancer effects of estriol.
  • Estriol should be combined with estradiol for breast cancer prevention. As discussed, the higher level of estriol, the lower the cancer. It is unconscionable not to make women aware of this.
    “Enough presumptive and scientific evidence has been accumulated that we may say that orally administered estriol is safer…let us have the estrogen that causes the least risk .”
    JAMA 1978

3. Women should be on cyclic progesterone (only 10-14 days per month)

  • The decreased amount of progesterone in cyclic administration of progesterone to have periods increases the risk of endometrial cancer (1,2,3) and breast cancer. (4,5).
    • 1. Gynecol Oncol, 1997
    • 2. Science, 1993
    • 3. Maturitas, 1992
    • 4. Fertil Steril. 1995
    • 5. Fertil Steril 1998
    • 6. Am J Epidemiol 1981

4. Dr. Schwarzbein states that doing the combined continuous method is like pregnancy and thus increases the risk of breast cancer.

  • Combined continuous is certainly not like pregnancy and has opposite effects on the endometrium. In addition, pregnancy is a strongly associated with breast cancer protection.
  • Women with multiple pregnancies have a lifetime exposure to the estrogen and progesterone that is 1.5-3 times that of women who have never been pregnant. This increased exposure (especially in estriol and progesterone) confers a significant reduction in cancer risk. If natural hormones caused cancer, opposite findings would be expected.
  • Some factors associated with pregnancy (high estriol and progesterone) are known to reduce a woman’s chance of developing breast cancer later in life.
    • The younger a woman has her first child, the lower her risk of developing breast cancer during her lifetime.
    • A woman who has her first child after the age of 35 has approximately twice the risk of developing breast cancer as a woman who has a child before age 20.
    • Having more than one child decreases a woman’s chances of developing breast cancer. In particular, having more than one child at a younger age decreases a woman’s chances of developing breast cancer during her lifetime.
      The National Cancer Institute

5. Dr. Schwarzbein states that doing the combined continuous method (not having periods) with natural progesterone increases insulin resistance.

  • While this is certainly true with progestins, it is been demonstrated not to be the case with natural progesterone.
    University of Massachusetts, Energy Metabolism Lab, 2003 Diabetes Care January 2002
  • I have followed the insulin levels on thousands of women on combined transdermal biestrogen and continuous progesterone. I have found that there is not only no adverse effect on the insulin resistance, but rather an improvement in insulin sensitivity.
  • In fact, it has been shown that it is not the continuous progesterone that results in an increased insulin resistance, but rather the effect of oral estrogen (natural estradiol included).
  • A 1993 study found that oral estrogen increased insulin resistance while transdermal did not.
    “Oral estrogen therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response…while the transdermal regimen had relatively few effects on insulin metabolism.”
    Metabolism 1993
  • A study published 2002 in the journal Diabetes Care looked at the effect that oral estradiol and continuous progesterone had on insulin resistance. 28 postmenopausal women were given oral estradiol with or without continuous progesterone and matched with women not taking any hormones.
  • The authors conclude that postmenopausal women taking oral estrogen, with or without progesterone, show a greater degree of insulin resistance than those not taking hormone replacement therapy, even allowing for total and abdominal adiposity.
  • The culprit was the oral estradiol and not the progesterone



    Insulin resistance increased with oral estradiol and was not effected by continuous oral progesterone.







Is Hormone Replacement Right for You?
(Bioidentical vs. Synthetic)
Kent Holtorf, M.D.

Below is a review of the medical literature demonstrating how natural hormones are superior to their synthetic counterparts. The conclusion is clear that bio-identical hormones are a safe alternative to Premarin and medroxyprogesterone acetate (MPA), marketed as Provera. The natural bio-identical hormones are very different from their synthetic versions, often having completely opposite physical and cellular effects. Thus, it is critical that women be given the information that these natural hormones do not have the negative side effects of the synthetic hormones and in no way pertain to the conclusions reached by the Women’s Health Initiative (WHI) study. Natural hormones are a safe and more conservative approach to hormone replacement therapy that does not carry the risks associated with Premarin and Provera.

We have found that patients feel great on the natural hormones, but when they are on synthetic hormones, they often do not fully respond or have considerable side-effects. Medical studies confirm that women report improved satisfaction when they are changed from MPA to progesterone and have an improved quality of life (2,50). The medical studies also show that HRT with bio-identical hormones are safer (1-79) and far superior to Premarin and Provera with better outcomes and fewer risks and side effects (1-79).

The WHI study demonstrated that when MPA was added to Premarin, there was a substantial increase in the risk of heart attack and stroke. This was an expected outcome with MPA, as it has clearly been shown to not only negate any cardioprotective effects of estrogen, but also to actually promote cardiovascular disease and increase the risk of heart attack and stroke (12,13,14,15,16,17,34,35,36,49,50,51,53,54,65,70,71,72,73). Natural estrogen and progesterone, on the other hand, have an opposite effect. They maintain and augment the cardioprotective effects of estrogen and decrease the risk of heart attack and stroke (49,50,61,67,70,71,72,76,77).

A number of other medical studies have shown that coronary artery spasm, which increases the risk of heart attack and stroke, can be reduced with estrogen and progesterone (13,14,15,68,69), but the addition of MPA to estrogen has the opposite effect and results in vasoconstriction (13,14,15,69), increasing the risk of heart attack and stroke in postmenopausal women. In a study where 18 monkeys had their ovaries removed to simulate menopause, they were then put on estradiol plus either Provera or natural progesterone. After 4 weeks, the researchers injected a substance that causes the coronary arteries to constrict, cutting off the flow of blood to the heart muscle. The researchers reported that the animals receiving Provera would have died within minutes had they not received protective drug treatment. Those on the natural progesterone required no such treatment. The researchers summarized, “We conclude that medroxyprogesterone (Provera) in contrast to progesterone increases the risk of coronary vasospasm (13).” This coronary spasm induced by MPA acetate, but not progesterone, results in an increased risk of heart attack and stroke with MPA use but not with natural progesterone use.

Researchers compared the effects of estrogen and progesterone with estrogen and medroxyprogesterone on exercise induced myocardial ischemia (lowered blood flow) in postmenopausal women with coronary artery disease. This was a blinded randomized crossover study. Women were placed on estradiol for four weeks. They were then randomized to receive either natural progesterone or Provera along with the estradiol. After 10 days on the combined treatment the patients then underwent a treadmill test. The patients then crossed over to the opposite treatment and repeated the treadmill. It was found that exercise time to myocardial ischemia was increased with natural progesterone (decreased risk of heart attack) vs. Provera. They state, “These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration. Provera is expected to increase the risk of heart attack and stroke while progesterone is not (14).” This coronary dilatation, produced by natural progesterone, but not MPA, increases blood flow to the heart and decreases the risk of heart attack and stroke.

In a series of studies, Adams (51,61), studied the cardioprotective effects of estrogen and progesterone verses estrogen and MPA. The estrogen and progesterone combination resulted in a 50% reduction in athrosclerotic plaque in the coronary arteries (61). This effect was independent of changes in lipid concentrations. However, when MPA was combined with estrogen, almost all of the cardioprotective effect (athrosclerotic plaque reduction) was reversed and negated (51). MPA was also shown to increase insulin and glucose levels, further increasing the risk of heart disease, heart attack and stroke (51). A number of additional studies have also shown that progesterone by itself (76,77) or in combination with estrogen (51,61 and 15) will inhibit athrosclerotic plaque formation. Synthetic progestins, on the other hand, have a completely opposite effect. They promote athrosclerotic plaque formation and inhibit any plaque inhibiting action of estrogen (51,15,53,54). This anti-athrogenic (inhibits plaque formation) effect of progesterone is directly opposite to the effects of synthetic progestins, which is pro-athrogenic (promotes plaque formation). In addition, MPA is unique in that it is shown to increase the amount of collagen in vascular plaques, which promotes thrombus (clot) formation (54,15). This increases the risk of heart attack, stroke and blood clots. Again, there are significant differences in natural progesterone and synthetic progestins, with the former reducing the risk of heart disease, heart attacks, and strokes, while the latter increases the risk of heart disease, heart attack, and stroke.

A review paper by Clarkson, published in the Journal of Reproductive Medicine and entitled Progestogens [term for all progesterone like compounds including progesterone and progestins] and Cardiovascular Disease-A Critical Review, the negative effects of MPA in comparison to progesterone were discussed. The authors summarize, “Of particular interest is the attenuating effect medroxyprogesterone acetate (MPA) has on the cardiovascular benefits of postmenopausal estrogen treatment. MPA reduces the dilatory effect of estrogens on coronary arteries, increases the progression of coronary artery arteriosclerosis, accelerates low-density lipoprotein uptake in plaque, increases the thrombogenic potential of atherosclerotic plaques and promotes insulin resistance and its consequent hyperglycemia. These effects may be largely limited to MPA and not shared with other progestogens.” They boldly display in the middle of the page a summary stating, “The data strongly suggests caution in the use of MPA…” and list as their summary of findings that “These studies, taken together, provide a basis for concern, not about all progestogens, but specifically about MPA(15).” Again, after a review of the literature, it is of no surprise, rather it was expected that the MPA arm of the WHI study would show an increased risk of coronary and cerebral vascular events.

Estrogen and progesterone are superior to estrogen and Provera in the effects on HDL cholesterol. In the large PEPI trial (11), 875 postmenopausal women were randomized to receive either placebo, Premarin, Premarin and Provera, or Premarin and natural Progesterone. This study demonstrates the superior effect of natural progesterone over Provera. HDL (good cholesterol was increased by 9% when estrogen and natural progesterone were used versus just a 3-4% increase with estrogen and Provera. The investigators were surprised by the superiority of natural progesterone over synthetic Provera (34) with Dr. Healy, a PEPI trial investigator, stating, “I think the biggest surprise certainly was the HDL effect of micronized progesterone. And I quite agree with Dr. Barrett-Connor that any ongoing trial now, whether they be the National Heart, Lung Blood Institute study on estrogen in women who have known coronary disease or the Women’s Health Initiative, should relook reexamine at the regimens being offered.” Elizabeth Connor, Cardiologist and PEPI investigator, stated, “If I were treating a women primarily because she was worried about heart disease or because she has dyslipidemia and low HDL cholesterol, I would probably see if she wanted to take micronized [natural] progesterone. I was quite impressed with the better effect (12).”

Many experts were surprised when the PEPI trial demonstrated that MPA, but not progesterone, significantly attenuated the positive effects of estrogen on lipids. The opposing effects of MPA and progesterone on this cardiovascular risk factor have previously, however, been clearly shown, with MPA and other synthetic progestins negating the positive effects of estrogen on lipids (63,64,65,70 ,72) while progesterone either maintains or augments estrogen’s positive effects on lipids (66,67,70,71,72). Thus, based on their effects on lipids, progesterone would be expected to decrease the risk of heart disease and stroke, while synthetic progestins such as Provera would be expected to increase the risk of heart attack and stroke.

Based on the results from the PEPI Trial and other studies (11,74), the President of the American Heart Association stated that, just based on this difference in the effects on HDL, a women who changes her medication from MPA to natural progesterone would significantly lower her risk for heart disease (35). The differing effects of progestins and progesterone on lipids is another risk factor that results in an increased risk for heart disease, heart attack and stroke when the synthetic is used but not natural progesterone.

MPA and synthetic progestins are also shown to significantly increase, even double (52,73,49,75) the amount of insulin resistance (Type II diabetes) when compared to estrogen alone or estrogen and progesterone (52,62,73,49). Thus, synthetic progestins are expected to promote vascular disease and increase the risk of heart attack and stroke while natural progesterone does not possess this detrimental effect.

Progesterone was compared to Provera for its ability to decrease the formation of a protein that initiates athrogenic plaques (coronary artery disease), vascular cell adhesion molecule-1. It was shown that progesterone clearly inhibited this protein, but medroxyprogetreone acetate (MPA) (Provera) did not. The authors write, “Because the expression of VCAM-1 is one of the earliest events that occur in the atherogenic process, this adhesion molecule might be the target of progesterone on vascular walls. The contrasting effects of progesterone and MPA seem clinically important, inasmuch as MPA is a widely used progestin in the regimen of hormone replacement therapy (32).” This is another process in which MPA promotes heart disease and the risk of heart attack and stroke, while progesterone reduces heart disease and the risk of heart attack and stroke.

Doctor Lignieres, from, the Necker Hospital Department of Endocrinology and Reproductive Medicine in Paris, France, reviewed the scientific literature that compared natural oral micronized progesterone and commonly used progestins and published his findings in a 1999 Journal, Clinical Therapeutics. He writes, “…most commonly used synthetic progestins, norethisterone and medroxyprogesterone acetate, have been associated with metabolic and vascular side effects (e.g., suppression of the vasodilating effect of estrogens) in both experimental and human controlled studies. All comparative studies to date conclude that the side effects of synthetic progestins can be minimized or eliminated through the use of natural progesterone…(49).”

A review of progesterone verses synthetic progestins was done by Fitzpatrick from the department of Internal Medicine at the Mayo Clinic. In this review, entitled Micronized Progesterone: Clinical Indications and Comparison with Current Treatments and was published in Fertility and Sterility, the author summarizes the study’s findings, “A large body of evidence, including the Postmenopausal Estrogen/Progestin Interventions study, suggests that the use of combination estrogen and oral micronized progesterone is optimal for long term hormone replacement therapy…However, use of progesterone-like hormones (progestins) is associated with a number of potential adverse reactions, including bleeding, amenorrhea, and, at higher doses, somnolence. There is also evidence that synthetic progestins have a teratogenic effect when administered during the first 4 months of pregnancy. Treatment with combined estrogen and progestin medication impairs glucose tolerance in some patients (62). The synthetic progestins also may attenuate the beneficial lipid and cardioprotective effects of concomitantly administered estrogen (63,64). Because of the potential adverse reactions, careful medical oversight is required if the synthetic progestins are to be used during the first trimester of pregnancy or by patients with diabetes, hyperlipidemia, or hypertension. For indications in which oral delivery of synthetic progestins currently are used, the theoretic benefits of oral delivery of the natural form of the hormone are obvious. In addition to the decreased potential for adverse effects, there are clear advantages in convenience, cost, compliance, and quality of life (50).”

Premarin, being an oral estrogen, will increase clotting factors and inflammatory proteins, increasing the risk of thromboembolism, stroke and heart attack (16,18). This does not occur with transdermal estrogens (18). In fact, it can be considered malpractice to give oral contraceptives or oral HRT to smokers because of the increased risk of stroke, but non-smokers are at increased risk, as well. When oral Premarin is taken with Provera the risk of thromboembolism, stroke and heat attack increase in a synergistic manner. Ninety percent of my patients are on transdermal natural estrogens for this reason (18).

The Nurses Health Study followed 58,000 postmenopausal women for 16 years (725,000 person-years). The study found that, compared with women who never used hormones, use of unopposed postmenopausal estrogen from ages 50 to 60 years increased the risk of breast cancer to age 70 by 23%. The addition of a progestin to the estrogen replacement resulted in a tripling of the risk of breast cancer to a 67% increase in the risk of breast cancer (78)(9).

A large study compared the risk of breast cancer in 1897 women on combined estrogen and progestin versus 1637 controls that had never used any HRT. It was found that the use of progestin increased the risk of breast cancer by 38%. The authors conclude, “This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone (10).” Again, natural progesterone is documented to reduce the risk of breast cancer.

Premarin is made from pregnant horses’ urine, hence its name Pre (pregnant)-mar (horse)- in (urine). It consists of a combination of conjugated equine (horse) estrogens that are more potent and more carcinogenic than other natural estrogens such as estradiol and especially estriol. 4-hydroxyequilenin, a component of Premarin, is especially potent, 100 times the potency of natural estrogen, and carcinogenic.(20,21,22,80). One author summarizes, “These results suggest that 4-hydroxyequilenin has the potential to be a potent carcinogen through the formation of variety of DNA lesions in vivo (22).” Natural estrogens have no such carcinogenic metabolites.

The natural estrogen, estriol, is shown to cause much less breast cell proliferation and is felt to be a much safer form of estrogen than even estradiol and especially Premarin (23,24,39,25,26,27). Estriol is shown to decrease the incidence and inhibit breast cancer in rats (24,39,26), while the levels of estriol in a women are inversely correlated with the risk of breast cancer, with low levels being associated with cancer while high levels are protective (25,26,56,57,59,60). An analysis of 6 epidemiologic studies of estrogen levels in women found that there are higher estriol levels in populations with lower risks for breast cancer (26).

Dr. Follingstad published an article in the Journal of the American Medical association, titled, Estriol, the forgotten estrogen? He reviewed a study in which estriol was given to postmenopausal women with breast cancer. Thirty-seven percent of the patients demonstrated remission or arrest of the disease. He concluded that estriol should be given to all women who need estrogen replacement therapy but are at risk for breast cancer. A case can be made that all women are at risk and estriol should be part of all HRT regimens. He writes, “Enough presumptive and scientific evidence has been accumulated that we may say that orally administered estriol is safer than estrone or estradiol…let us have the estrogen that causes the least risk (27).”

In a large study that looked at the effect of estrogens on breast cancer in rats, it was shown that estriol was protective. The authors felt that “The superior protective action of estriol may be partly related to its greater solubility in plasma and decreased binding to plasma-albumin, compared to oestrone [estrone] or 17B-oestradiol [estradiol] (58.)” Premarin on the contrary increases the risk of breast cancer (20,21,22,80).

There has been considerable research in estrogen metabolism and its relation to breast cancer. Estradiol can be metabolized to either a potent carcinogenic compound, 16-hydroxyestrone, or to a noncarcinogenic compound, 2-hydroxyestrone. Women who metabolize estradiol to 16-hydroxyestrone have a significantly increased risk for breast cancer, and it is being realized that these metabolites likely play a major role in the incidence of breast cancer (40-48). In a study by Kabat et al, entitled Urinary Estrogen Metabolites and Breast Cancer: A Case Controlled Study, it was found that postmenopausal women with the highest levels of 16-hydroxyestrone compared to 2-hydroxyestrone were shown to have a risk factor for breast cancer that was 32 times that of controls. I routinely check these levels in women and determine the ratios because they have a profound effect on breast cancer risk. Interestingly, women with family histories of breast cancer will usually have elevated 16-hydroxyestrone. If an increased level of the carcinogenic estrone is present, measures are taken to reverse this metabolization pattern and then the levels are re-checked. Estriol, however, does not convert to the carcinogenic 2-hydroxyestrone, making it a much a safer form of estrogen.

Estriol also improves multiple sclerosis while other estrogens make it worse; another indication of its profoundly different effects. (28,29)

A number of studies demonstrate that synthetic progestins, such as Provera, increase breast cell proliferation (4,5,7,9,33,79,19,81), making it pro-carcinogenic and increases the risk of breast cancer (6,7,8,9,10,55,19). This cell proliferation with Provera has been shown to be particularly bad (7). This increased cell proliferation, as expected, translates into an increased risk of breast cancer with medroxyprogesterone use. Natural progesterone, as opposed to medroxyprogsterone, has a strong anti-proliferate effect on breast tissue (1,8,81). This is the opposite effect of Provera and results in a strong anti-breast cancer effect of natural progesterone (30,31,1,8), again opposite of Provera.

A double blind placebo controlled study looked at the effects of estrogen and progesterone on women prior to breast surgery. Patients were given either a placebo, estrogen, or estrogen and progesterone for 10-13 days prior to breast surgery. Estradiol increased cell proliferation rates by 230%, but progesterone decreased cell proliferation rates by 400%. The progesterone, when given with estradiol, inhibited and prevented any breast proliferation (cancer preventive). (1) Progestins do not have this beneficial effect.

In a double blind randomized study, Foidart et al also showed that progesterone eliminated estrogen produced breast cell proliferation (8), demonstrating the strong anti-proliferative and anti-cancer effect of natural progesterone. This effect is opposite of that of synthetic progestins, which increase proliferation and increase the risk of breast cancer (4,5,7,9,33,78,79,19).

A prospective epidemiological study conducted at Johns Hopkins demonstrated the profound anti-breast cancer action and protective role of natural progesterone against breast cancer. In that study, 1083 women who had been evaluated and treated for infertility were followed for 13 to 33 years. The results showed that the risk of breast cancer was 5.4 times in subjects who had a low progesterone level when compared to those with a normal level. This was particularly striking because the result was so significant despite the fact that the high progesterone group actually had significantly more risk factors for breast cancer than the low progesterone group, indicating that the progesterone level is a far more important parameter. Additionally, women in the low progesterone group experienced 10 times more deaths from neoplasm (cancer) when compared to those with normal progesterone (30).

In another study, the protective effect of progesterone or Tamoxifen, a potent estrogen antagonist, was investigated in estrogen-induced breast cancer in rats. Results of the study indicated that the induction rate, multiplicity, and size of estrogen induced mammary tumors were reduced by simultaneous administration of either Tamoxifen or progesterone. (31) Natural progesterone is also shown to reduce the number of estrogen receptors in breast tissue (anti-cancer effect).(3)

These studies indicate that, with respect to the risk of breast cancer, heart disease, heart attacks and stroke, natural hormones offer a safe and more conservative approach to HRT. The large amount of scientific evidence that overwhelmingly demonstrates that natural hormones are safer than the study drugs of the WHI, Premarin and Provera. Unfortunately, the overwhelming majority of women do not know that there are safe alternatives to their current HRT or to the one they stopped after the results of the WHI were released. As you can see, it is clear that the negative outcome of the WHI study with the use of MPA is certainly of no surprise, given its clear history of having a negative impact on almost every risk factor for heart disease. Natural progesterone has just an opposite effect of MPA on almost every cardiac risk factor, with MPA increasing the risk of heart attack and stroke, while progesterone decreases the risk. If progesterone was used in the trial, the results would assuredly have been different and their results in no way pertain to natural hormones, which are a safe choice with significantly less risk.

The same is true of the increased incidence of breast cancer demonstrated in the study with the use of Premarin and MPA. This in no way pertains to the use of the natural hormones; estriol and progesterone, which both decrease the risk of breast cancer. The public, and also doctors, need to be told that there is a safer alternative to Premarin and Provera and that HRT should not be abandoned based on the results of a known toxic drug combination. It is the utmost importance for women to understand that they have alternatives to Premarin and Provera that are scientifically shown to be safer and healthier.




WHI Study Confusion



WHI Study Confusion
Kent Holtorf, M.D.

There is a lot of confusion about the meaning of the recent study known as the Women’s Health Initiative, which was testing the effects of the most prescribed drug combination hormone replacement therapy for menopausal women, Premarin (conjugated equine estrogens) and Provera (medroxyprogesterone acetate). This study was halted because the use of the study drugs, Premarin and Provera (also in PremPro), increased the risk of breast cancer, heart attack, blood clots, and stroke. This was actually an expected outcome for this particular medication, which combines an oral horse estrogen and a synthetic progestin, because this combination has been shown on numerous occasions to have precisely these problems. For years, many doctors have been discouraging patients from taking synthetic hormones and encouraging them to switch to natural prescription hormones that are shown to be more beneficial and to not have the risks associated with the synthetic hormones. I have discouraged the use of this combination for many years and have gotten my patients off this combination and onto prescription natural estrogen and progesterone that are bioidentical to a woman’s natural hormones. These natural hormones do not have the negative side-effects or carry any of the risks demonstrated in the recent and past studies. The natural combinations have been shown to decrease the risk of stroke and heart attack by 50% (Premarin and Provera increase it) and reduce the risk of breast cancer by 80% (Premarin and Provera increase it). The natural hormones also reduce the risk of osteoporosis by 50%, reduce the risk of Alzheimer’s by 80%, reduce the risk of osteoarthritis by 40%, and reduce the risk of colon cancer by 40%.

There is a long history of studies showing that when a synthetic progestin (Provera) is used, there will be an increase in breast cancer, while the use of natural prescription progesterone will have a powerful protective effect against breast and other cancers. Studies show that women with low levels of progesterone are up to 10 times more likely to develop cancer and 5 times more likely to develop breast cancer. Natural progesterone has strong anti-cancer effects while synthetic progestins are carcinogenic. In fact, women taking natural estrogen and natural progesterone are provided protection against breast cancer and are at less risk of developing cancer when compared to women who are not on any hormone replacement therapy.

Progesterone is naturally produced by a woman, but because the drug companies cannot patent this natural hormone, they must first alter the molecule so they can patent it to make it financially worth while to market and sell. When this was done, some of progesterone’s effects were retained, while other effects were opposite of those produced by natural progesterone. For instance, progesterone is secreted in high doses by women during pregnancy to promote fetal growth. On the contrary, progestin during pregnancy will kill the fetus. The main ingredient in The Morning After Pill to terminate pregnancy is progestin. It was shown that Provera could protect the uterus from cancer from unopposed estrogen, and this is how it was approved. It was not known at that time, however, that it would not protect the breast from cancer like natural progesterone does. In fact, synthetic progestins such as Provera promote cancer. The alteration of the natural progesterone also changed the vasodilator effect of natural progesterone, which decreases the risk of heart attack and stroke, to a compound that constricts coronary arteries and other vessels, significantly increasing the risk for heart attack and stroke. It is also clear from numerous studies that taking synthetic progestins, such as Provera, will increase a woman’s risk for heart disease and will negate many potential positive benefits of estrogens. On the contrary, natural progesterone will augment the positive benefits. Provera has also been associated with increased fatigue, weight gain, and decreased exercise tolerance, while natural progesterone demonstrates none of these problems. Over the past 10 years there has been so much evidence that the synthetic progestins, such as Provera, are harmful that it would never have been approved by the FDA if the drug companies had sought approval in more recent years.

The Premarin used in the study added fuel to Provera’s toxic fire. Premarin, the most popular estrogen replacement therapy (ERT,) is derived from pregnant horses and contains mostly estrone and a number of equine (horse) estrogens that are not natural to humans. Many of these foreign estrogens bind very tightly to the human estrogen receptors, making them highly stimulating and carcinogenic. A combination of the natural estrogens, estriol and estridiol have been shown to actually protect against breast cancer and result in a reduction in breast cancer risk. When this is added to natural progesterone’s powerful breast cancer risk reduction, one would expect a significant reduction in breast cancer in women on natural hormone replacement than in women on no therapy. The hormones estriol and progesterone rise very high during pregnancy, which results in a successive decreasing risk of breast cancer the more times one is pregnant.

Also when Premarin is given orally, it passes through the liver and significantly increases clotting factors and risk for stroke and heart attack. This results in a multiplied heart attack risk when Provera is added. When estrogens are given transdermally patch or cream this problem is avoided. Synthetic progestins are toxic no matter which form is prescribed.

This study has unfortunately surprised many physicians even though this was truly an expected result of these synthetic hormones. In the many years that I have been preaching the dangers of Premarin and Provera many patients have asked me why then are so many doctors prescribing these hormones. The answer is multifactorial. First, many doctors are not aware of the studies showing the significant risks of this combination. Many people think that doctors are able to sit around and read medical journals, but unfortunately, most doctors do not have the time. Many rely on pharmaceutical representatives (the ones selling the drugs) to bring them new studies on their drugs, and obviously nothing negative is brought in. There are no pharmaceutical representatives selling natural prescription estrogens and progesterone. Secondly, drug selection by physicians is driven by insurance companies, who decide which drugs the physicians may use by deciding which drugs are on their formularies. Insurance companies encourage the use of Premarin, Provera and PremPro because they are economically priced and they have been the standard treatment for many years. They make it difficult for a doctor to choose another drug. Thirdly, many doctors are creatures of habit. Once they become comfortable with a drug it is difficult to get them to change. Many doctors also felt that the problems were not that bad and besides everyone else was using them.

In summary, this study has opened the eyes of many, but it has also closed the eyes of many. In that some will understand what this study indicates, while others will misinterpret the study and come to the wrong conclusion that women are better off not on any hormone replacement therapy. Consequently, many women will needlessly suffer and be at increased risk for heart disease, stroke and multiple cancers. There is a fast growing interest in the natural hormones, despite the fact it is not backed by a multi-billion dollar drug company because they don’t have the risks associated with their synthetic counterparts. Many more women are demanding them and many more doctors are prescribing them for their superior properties and safety. I recommend women find a doctor who is well versed in these natural bio-identical prescription hormone replacement therapies.

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Natural (Bio-identical) vs. Synthetic HRT



Natural (Bio-identical) vs. Synthetic HRT
Kent Holtorf, M.D.

Below is a review of the medical literature demonstrating how natural hormones are superior to their synthetic counterparts. The conclusion is clear that bio-identical hormones are a safe alternative to Premarin and medroxyprogesterone acetate (MPA), marketed as Provera. The natural bio-identical hormones are very different from their synthetic versions, often having completely opposite physical and cellular effects. Thus, it is critical that women be given the information that these natural hormones do not have the negative side effects of the synthetic hormones and in no way pertain to the conclusions reached by the Women’s Health Initiative (WHI) study. Natural hormones are a safe and more conservative approach to hormone replacement therapy that does not carry the risks associated with Premarin and Provera.

I have found that patients feel great on the natural hormones, but when they are on synthetic hormones, they often do not fully respond or have considerable side-effects. Medical studies confirm that women report improved satisfaction when they are changed from MPA to progesterone and have an improved quality of life (2,50). The medical studies also show that HRT with bio-identical hormones are safer (1-79) and far superior to Premarin and Provera with better outcomes and fewer risks and side effects (1-79).

The WHI study demonstrated that when MPA was added to Premarin, there was a substantial increase in the risk of heart attack and stroke. This was an expected outcome with MPA, as it has clearly been shown to not only negate any cardioprotective effects of estrogen, but also to actually promote cardiovascular disease and increase the risk of heart attack and stroke (12,13,14,15,16,17,34,35,36,49,50,51,53,54,65,70,71,72,73). Natural estrogen and progesterone, on the other hand, have an opposite effect. They maintain and augment the cardioprotective effects of estrogen and decrease the risk of heart attack and stroke (49,50,61,67,70,71,72,76,77).

A number of other medical studies have shown that coronary artery spasm, which increases the risk of heart attack and stroke, can be reduced with estrogen and progesterone (13,14,15,68,69), but the addition of MPA to estrogen has the opposite effect and results in vasoconstriction (13,14,15,69), increasing the risk of heart attack and stroke in postmenopausal women. In a study where 18 monkeys had their ovaries removed to simulate menopause, they were then put on estradiol plus either Provera or natural progesterone. After 4 weeks, the researchers injected a substance that causes the coronary arteries to constrict, cutting off the flow of blood to the heart muscle. The researchers reported that the animals receiving Provera would have died within minutes had they not received protective drug treatment. Those on the natural progesterone required no such treatment. The researchers summarized, “We conclude that medroxyprogesterone (Provera) in contrast to progesterone increases the risk of coronary vasospasm (13).” This coronary spasm induced by MPA acetate, but not progesterone, results in an increased risk of heart attack and stroke with MPA use but not with natural progesterone use.

Researchers compared the effects of estrogen and progesterone with estrogen and medroxyprogesterone on exercise induced myocardial ischemia (lowered blood flow) in postmenopausal women with coronary artery disease. This was a blinded randomized crossover study. Women were placed on estradiol for four weeks. They were then randomized to receive either natural progesterone or Provera along with the estradiol. After 10 days on the combined treatment the patients then underwent a treadmill test. The patients then crossed over to the opposite treatment and repeated the treadmill. It was found that exercise time to myocardial ischemia was increased with natural progesterone (decreased risk of heart attack) vs. Provera. They state, “These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.” Provera is expected to increase the risk of heart attack and stroke while progesterone is not (14).” This coronary dilatation, produced by natural progesterone, but not MPA, increases blood flow to the heart and decreases the risk of heart attack and stroke.

In a series of studies, Adams (51,61), studied the cardioprotective effects of estrogen and progesterone verses estrogen and MPA. The estrogen and progesterone combination resulted in a 50% reduction in athrosclerotic plaque in the coronary arteries (61). This effect was independent of changes in lipid concentrations. However, when MPA was combined with estrogen, almost all of the cardioprotective effect (athrosclerotic plaque reduction) was reversed and negated (51). MPA was also shown to increase insulin and glucose levels, further increasing the risk of heart disease, heart attack and stroke (51). A number of additional studies have also shown that progesterone by itself (76,77) or in combination with estrogen (51,61 and 15) will inhibit athrosclerotic plaque formation. Synthetic progestins, on the other hand, have a completely opposite effect. They promote athrosclerotic plaque formation and inhibit any plaque inhibiting action of estrogen (51,15,53,54). This anti-athrogenic (inhibits plaque formation) effect of progesterone is directly opposite to the effects of synthetic progestins, which is pro-athrogenic (promotes plaque formation). In addition, MPA is unique in that it is shown to increase the amount of collagen in vascular plaques, which promotes thrombus (clot) formation (54,15). This increases the risk of heart attack, stroke and blood clots. Again, there are significant differences in natural progesterone and synthetic progestins, with the former reducing the risk of heart disease, heart attacks, and strokes, while the latter increases the risk of heart disease, heart attack, and stroke.

A review paper by Clarkson, published in the Journal of Reproductive Medicine and entitled Progestogens [term for all progesterone like compounds including progesterone and progestins] and Cardiovascular Disease-A Critical Review, the negative effects of MPA in comparison to progesterone were discussed. The authors summarize, “Of particular interest is the attenuating effect medroxyprogesterone acetate (MPA) has on the cardiovascular benefits of postmenopausal estrogen treatment. MPA reduces the dilatory effect of estrogens on coronary arteries, increases the progression of coronary artery arteriosclerosis, accelerates low-density lipoprotein uptake in plaque, increases the thrombogenic potential of atherosclerotic plaques and promotes insulin resistance and its consequent hyperglycemia. These effects may be largely limited to MPA and not shared with other progestogens.” They boldly display in the middle of the page a summary stating, “The data strongly suggests caution in the use of MPA…” and list as their summary of findings that “These studies, taken together, provide a basis for concern, not about all progestogens, but specifically about MPA.”(15). Again, after a review of the literature, it is of no surprise, rather it was expected that the MPA arm of the WHI study would show an increased risk of coronary and cerebral vascular events.

Estrogen and progesterone are superior to estrogen and Provera in the effects on HDL cholesterol. In the large PEPI trial (11), 875 postmenopausal women were randomized to receive either placebo, Premarin, Premarin and Provera, or Premarin and natural Progesterone. This study demonstrates the superior effect of natural progesterone over Provera. HDL (good cholesterol was increased by 9% when estrogen and natural progesterone were used versus just a 3-4% increase with estrogen and Provera. The investigators were surprised by the superiority of natural progesterone over synthetic Provera (34) with Dr. Healy, a PEPI trial investigator, stating, “I think the biggest surprise certainly was the HDL effect of micronized progesterone. And I quite agree with Dr. Barrett-Connor that any ongoing trial now, whether they be the National Heart, Lung Blood Institute study on estrogen in women who have known coronary disease or the Women’s Health Initiative, should relook reexamine at the regimens being offered.” Elizabeth Connor, Cardiologist and PEPI investigator, stated, “If I were treating a women primarily because she was worried about heart disease or because she has dyslipidemia and low HDL cholesterol, I would probably see if she wanted to take micronized [natural] progesterone. I was quite impressed with the better effect (12).”

Many experts were surprised when the PEPI trial demonstrated that MPA, but not progesterone, significantly attenuated the positive effects of estrogen on lipids. The opposing effects of MPA and progesterone on this cardiovascular risk factor have previously, however, been clearly shown, with MPA and other synthetic progestins negating the positive effects of estrogen on lipids (63,64,65,70 ,72) while progesterone either maintains or augments estrogen’s positive effects on lipids (66,67,70,71,72). Thus, based on their effects on lipids, progesterone would be expected to decrease the risk of heart disease and stroke, while synthetic progestins such as Provera would be expected to increase the risk of heart attack and stroke.

Based on the results from the PEPI Trial and other studies (11,74), the President of the American Heart Association stated that, just based on this difference in the effects on HDL, a women who changes her medication from MPA to natural progesterone would significantly lower her risk for heart disease (35). The differing effects of progestins and progesterone on lipids is another risk factor that results in an increased risk for heart disease, heart attack and stroke when the synthetic is used but not natural progesterone.

MPA and synthetic progestins are also shown to significantly increase, even double (52,73,49,75) the amount of insulin resistance (Type II diabetes) when compared to estrogen alone or estrogen and progesterone (52,62,73,49). Thus, synthetic progestins are expected to promote vascular disease and increase the risk of heart attack and stroke while natural progesterone does not possess this detrimental effect.

Progesterone was compared to Provera for its ability to decrease the formation of a protein that initiates athrogenic plaques (coronary artery disease), vascular cell adhesion molecule-1. It was shown that progesterone clearly inhibited this protein, but medroxyprogetreone acetate (MPA) (Provera) did not. The authors write, “Because the expression of VCAM-1 is one of the earliest events that occur in the atherogenic process, this adhesion molecule might be the target of progesterone on vascular walls. The contrasting effects of progesterone and MPA seem clinically important, inasmuch as MPA is a widely used progestin in the regimen of hormone replacement therapy (32).” This is another process in which MPA promotes heart disease and the risk of heart attack and stroke, while progesterone reduces heart disease and the risk of heart attack and stroke.

Doctor Lignieres, from, the Necker Hospital Department of Endocrinology and Reproductive Medicine in Paris, France, reviewed the scientific literature that compared natural oral micronized progesterone and commonly used progestins and published his findings in a 1999 Journal, Clinical Therapeutics. He writes, “…most commonly used synthetic progestins, norethisterone and medroxyprogesterone acetate, have been associated with metabolic and vascular side effects (e.g., suppression of the vasodilating effect of estrogens) in both experimental and human controlled studies. All comparative studies to date conclude that the side effects of synthetic progestins can be minimized or eliminated through the use of natural progesterone…(49).”

A review of progesterone verses synthetic progestins was done by Fitzpatrick from the department of Internal Medicine at the Mayo Clinic. In this review, entitled Micronized Progesterone: Clinical Indications and Comparison with Current Treatments and was published in Fertility and Sterility, the author summarizes the study’s findings, “A large body of evidence, including the Postmenopausal Estrogen/Progestin Interventions study, suggests that the use of combination estrogen and oral micronized progesterone is optimal for long term hormone replacement therapy…However, use of progesterone-like hormones (progestins) is associated with a number of potential adverse reactions, including bleeding, amenorrhea, and, at higher doses, somnolence. There is also evidence that synthetic progestins have a teratogenic effect when administered during the first 4 months of pregnancy. Treatment with combined estrogen and progestin medication impairs glucose tolerance in some patients (62). The synthetic progestins also may attenuate the beneficial lipid and cardioprotective effects of concomitantly administered estrogen (63,64). Because of the potential adverse reactions, careful medical oversight is required if the synthetic progestins are to be used during the first trimester of pregnancy or by patients with diabetes, hyperlipidemia, or hypertension. For indications in which oral delivery of synthetic progestins currently are used, the theoretic benefits of oral delivery of the natural form of the hormone are obvious. In addition to the decreased potential for adverse effects, there are clear advantages in convenience, cost, compliance, and quality of life (50).”

Premarin, being an oral estrogen, will increase clotting factors and inflammatory proteins, increasing the risk of thromboembolism, stroke and heart attack (16,18). This does not occur with transdermal estrogens (18). In fact, it can be considered malpractice to give oral contraceptives or oral HRT to smokers because of the increased risk of stroke, but non-smokers are at increased risk, as well. When oral Premarin is taken with Provera the risk of thromboembolism, stroke and heat attack increase in a synergistic manner. Ninety percent of my patients are on transdermal natural estrogens for this reason (18).

The Nurses Health Study followed 58,000 postmenopausal women for 16 years (725,000 person-years). The study found that, compared with women who never used hormones, use of unopposed postmenopausal estrogen from ages 50 to 60 years increased the risk of breast cancer to age 70 by 23%. The addition of a progestin to the estrogen replacement resulted in a tripling of the risk of breast cancer to a 67% increase in the risk of breast cancer (78)(9).

A large study compared the risk of breast cancer in 1897 women on combined estrogen and progestin versus 1637 controls that had never used any HRT. It was found that the use of progestin increased the risk of breast cancer by 38%. The authors conclude, “This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone (10).” Again, natural progesterone is documented to reduce the risk of breast cancer.

Premarin is made from pregnant horses’ urine, hence its name Pre (pregnant)-mar (horse)- in (urine). It consists of a combination of conjugated equine (horse) estrogens that are more potent and more carcinogenic than other natural estrogens such as estradiol and especially estriol. 4-hydroxyequilenin, a component of Premarin, is especially potent, 100 times the potency of natural estrogen, and carcinogenic.(20,21,22,80). One author summarizes, “These results suggest that 4-hydroxyequilenin has the potential to be a potent carcinogen through the formation of variety of DNA lesions in vivo (22).” Natural estrogens have no such carcinogenic metabolites.

The natural estrogen, estriol, is shown to cause much less breast cell proliferation and is felt to be a much safer form of estrogen than even estradiol and especially Premarin (23,24,39,25,26,27). Estriol is shown to decrease the incidence and inhibit breast cancer in rats (24,39,26), while the levels of estriol in a women are inversely correlated with the risk of breast cancer, with low levels being associated with cancer while high levels are protective (25,26,56,57,59,60). An analysis of 6 epidemiologic studies of estrogen levels in women found that there are higher estriol levels in populations with lower risks for breast cancer (26).

Dr. Follingstad published an article in the Journal of the American Medical association, titled, Estriol, the forgotten estrogen? He reviewed a study in which estriol was given to postmenopausal women with breast cancer. Thirty-seven percent of the patients demonstrated remission or arrest of the disease. He concluded that estriol should be given to all women who need estrogen replacement therapy but are at risk for breast cancer. A case can be made that all women are at risk and estriol should be part of all HRT regimens. He writes, “Enough presumptive and scientific evidence has been accumulated that we may say that orally administered estriol is safer than estrone or estradiol…let us have the estrogen that causes the least risk (27).”

In a large study that looked at the effect of estrogens on breast cancer in rats, it was shown that estriol was protective. The authors felt that “The superior protective action of estriol may be partly related to its greater solubility in plasma and decreased binding to plasma-albumin, compared to oestrone [estrone] or 17B-oestradiol [estradiol] (58)” Premarin on the contrary increases the risk of breast cancer (20,21,22,80).

There has been considerable research in estrogen metabolism and its relation to breast cancer. Estradiol can be metabolized to either a potent carcinogenic compound, 16-hydroxyestrone, or to a noncarcinogenic compound, 2-hydroxyestrone. Women who metabolize estradiol to 16-hydroxyestrone have a significantly increased risk for breast cancer, and it is being realized that these metabolites likely play a major role in the incidence of breast cancer (40-48). In a study by Kabat et al, entitled Urinary Estrogen Metabolites and Breast Cancer: A Case Controlled Study, it was found that postmenopausal women with the highest levels of 16-hydroxyestrone compared to 2-hydroxyestrone were shown to have a risk factor for breast cancer that was 32 times that of controls. I routinely check these levels in women and determine the ratios because they have a profound effect on breast cancer risk. Interestingly, women with family histories of breast cancer will usually have elevated 16-hydroxyestrone. If an increased level of the carcinogenic estrone is present, measures are taken to reverse this metabolization pattern and then the levels are re-checked. Estriol, however, does not convert to the carcinogenic 2-hydroxyestrone, making it a much a safer form of estrogen.

Estriol also improves multiple sclerosis while other estrogens make it worse; another indication of its profoundly different effects. (28,29)

A number of studies demonstrate that synthetic progestins, such as Provera, increase breast cell proliferation (4,5,7,9,33,79,19,81), making it pro-carcinogenic and increases the risk of breast cancer (6,7,8,9,10,55,19). This cell proliferation with Provera has been shown to be particularly bad (7). This increased cell proliferation, as expected, translates into an increased risk of breast cancer with medroxyprogesterone use. Natural progesterone, as opposed to medroxyprogsterone, has a strong anti-proliferate effect on breast tissue (1,8,81). This is the opposite effect of Provera and results in a strong anti-breast cancer effect of natural progesterone (30,31,1,8), again opposite of Provera.

A double blind placebo controlled study looked at the effects of estrogen and progesterone on women prior to breast surgery. Patients were given either a placebo, estrogen, or estrogen and progesterone for 10-13 days prior to breast surgery. Estradiol increased cell proliferation rates by 230%, but progesterone decreased cell proliferation rates by 400%. The progesterone, when given with estradiol, inhibited and prevented any breast proliferation (cancer preventive). (1) Progestins do not have this beneficial effect.

In a double blind randomized study, Foidart et al also showed that progesterone eliminated estrogen produced breast cell proliferation (8), demonstrating the strong anti-proliferative and anti-cancer effect of natural progesterone. This effect is opposite of that of synthetic progestins, which increase proliferation and increase the risk of breast cancer (4,5,7,9,33,78,79,19).

A prospective epidemiological study conducted at Johns Hopkins demonstrated the profound anti-breast cancer action and protective role of natural progesterone against breast cancer. In that study, 1083 women who had been evaluated and treated for infertility were followed for 13 to 33 years. The results showed that the risk of breast cancer was 5.4 times in subjects who had a low progesterone level when compared to those with a normal level. This was particularly striking because the result was so significant despite the fact that the high progesterone group actually had significantly more risk factors for breast cancer than the low progesterone group, indicating that the progesterone level is a far more important parameter. Additionally, women in the low progesterone group experienced 10 times more deaths from neoplasm (cancer) when compared to those with normal progesterone (30).

In another study, the protective effect of progesterone or Tamoxifen, a potent estrogen antagonist, was investigated in estrogen-induced breast cancer in rats. Results of the study indicated that the induction rate, multiplicity, and size of estrogen induced mammary tumors were reduced by simultaneous administration of either Tamoxifen or progesterone. (31) Natural progesterone is also shown to reduce the number of estrogen receptors in breast tissue (anti-cancer effect).(3)

These studies indicate that, with respect to the risk of breast cancer, heart disease, heart attacks and stroke, natural hormones offer a safe and more conservative approach to HRT. The large amount of scientific evidence that overwhelmingly demonstrates that natural hormones are safer than the study drugs of the WHI, Premarin and Provera. Unfortunately, the overwhelming majority of women do not know that there are safe alternatives to their current HRT or to the one they stopped after the results of the WHI were released. As you can see, it is clear that the negative outcome of the WHI study with the use of MPA is certainly of no surprise, given its clear history of having a negative impact on almost every risk factor for heart disease. Natural progesterone has just an opposite effect of MPA on almost every cardiac risk factor, with MPA increasing the risk of heart attack and stroke, while progesterone decreases the risk. If progesterone was used in the trial, the results would assuredly have been different and their results in no way pertain to natural hormones, which are a safe choice with significantly less risk.

The same is true of the increased incidence of breast cancer demonstrated in the study with the use of Premarin and MPA. This in no way pertains to the use of the natural hormones; estriol and progesterone, which both decrease the risk of breast cancer. The public, and also doctors, need to be told that there is a safer alternative to Premarin and Provera and that HRT should not be abandoned based on the results of a known toxic drug combination. It is the utmost importance for women to understand that they have alternatives to Premarin and Provera that are scientifically shown to be safer and healthier.

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Selected References



Selected References

1. Chang HJ, Lee TTY et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril. 1995;63:785-791.

2. Fitzpatrick La et al. Comparison of regimens containing oral micronized progesterone of medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Women's Health Gen Based Med 2000 Mayu;9(4):381-7

3. Gompel et al. Antiestrogen action of progesterone in breast tissue. Breast cancer Res Treat 1986; 8(3):179-88.

4. Van der Burg et al. Effects of progestins on the proliferation of estrogen-dependent human breast cancer cells under growth factor-defined conditions. J Steroid Biochem Mol Biol 1992 Jun;42(5):457-65.

5. Mol JA; van Garderen E; Rutteman GR; Rijnberk A. New insights in the molecular mechanism of progestin-induced proliferation of mammary epithelium: induction of the local biosynthesis of growth hormone (GH) in the mammary glands of dogs, cats and humans. J Steroid Biochem Mol Biol 1996 Jan; 57(1-2):67-71.

6. Hulka BS, Links between hormone replacement therapy and neoplasia. Fertil Steril 1994 Dec;62(6 Suppl 2):168S-175S.

7. Hofseth LJ; Raafat AM; Osuch JR; Pathak DR; Slomski CA; Haslam SZ Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J Clin Endocrinol Metab 1999 Dec;84(12):4559-65.

8. Foidart JM; Colin C; Denoo X; Desreux J; Beliard A; Fournier S; de Lignieres B. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril 1998 May;69(5):963-9

9. Colditz GA; Rosner B Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am J Epidemiol 2000 Nov 15;152(10):950-64

10. Ross RK; Paganini-Hill A; Wan PC; Pike MC. Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst 2000 Feb 16;92(4):328-32.

12. Estrogen Replacement therapy and Heart Disease: A Discussion of the PEPI Trial. Women’s Health Information Center.

13. Miyagawa K; Rosch J; Stanczyk F; Hermsmeyer K. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med 1997 Mar;3(3):324-7.

14. Rosano GM; Webb CM; Chierchia S; Morgani GL; Gabraele M; Sarrel PM; de Ziegler D; Collins P. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol 2000 Dec;36(7):2154-9.

15. Clarkson TB. Progestogens and cardiovascular disease. A critical review. J Reprod Med 1999 Feb;44(2 Suppl):180-4

16. Feeman WE. Thrombotic stroke in an otherwise healthy middle-aged female related to the use of continuous-combined conjugated equine estrogens and medroxyprogesterone acetate. J Gend Specif Med 2000 Nov-Dec;3(8):62-4; discussion 64-5.

17. Sitruk-Ware R. Progestins and cardiovascular risk markers. Steroids 2000 Oct-Nov;65(10-11):651-8.

18. Scarabin PY; Alhenc-Gelas M; Plu-Bureau G; Taisne P; Agher R; Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial Arterioscler Thromb Vasc Biol 1997 Nov;17(11):3071-8

19. Colditz Ga. Hormones and breast cancer: evidence and implications for consideration of risks and benefits of hormone replacement therapy. J Women's Health 1999 Apr;8(3):354-7.

20. Zhang F; Chen Y; Pisha E; Shen L; Xiong Y; van Breemen RB; Bolton JL. The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone. Chem Res Toxicol 1999 Feb;12(2):204-13.

21. Pisha E; Lui X; Constantinou AI; Bolton JL Evidence that a metabolite of equine estrogens, 4-hydroxyequilenin, induces cellular transformation in vitro. Chem Res Toxicol 2001 Jan;14(1):82-90

22. Zhang F; Swanson SM; van Breemen RB; Liu X; Yang Y; Gu C; Bolton JL. Equine estrogen metabolite 4-hydroxyequilenin induces DNA damage in the rat mammary tissues: formation of single-strand breaks, apurinic sites, and stable adducts, and oxidized bases. Chem Res Toxicol 2001 Dec;14(12):1654-9

23. Tzingounis VA; Aksu MF; Greenblatt RB Estriol in the management of the menopause JAMA 1978 Apr 21;239(16):1638-41.

24. Lemon HM; Kumar PF; Peterson C; Rodriguez-Sierra JF; Abbo KM Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen. Cancer 1989 May 1;63(9):1685-92.

25. Lemon HM; Wotiz HH; Parsons L; Mozden PJ Reduced estriol excretion in patients with breast cancer prior to endocrine therapy. JAMA 1966 Jun 27;196(13):1128-36.

26. Lemon, H.M. Pathophysiologic considerations tin the treatment of menopausal patients with oestrogens; the role of oestriol in the prevention of mammary carcinoma. Acta Endocrinol Suppl 1980 233:17-27. DNH

27. Follingstad AH Estriol, The Forgotten Estrogen. JAMA Jan 2 1978, 239(1) p29-30

28. Kim S; Liva SM; Dalal MA; Verity MA; Voskuhl RR Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 1999 Apr 12;52(6):1230-8.

29. Bansil S; Lee HJ; Jindal S; Holtz CR; Cook SD. Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Acta Neurol Scand 1999 Feb;99(2):91-4

30. Cowan LD; Gordis L; Tonascia JA; Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol 1981 Aug;114(2):209-17

31. Inoh A; Kamiya K; Fujii Y; Yokoro K Protective effects of progesterone and tamoxifen in estrogen-induced mammary carcinogenesis in ovariectomized W/Fu rats. Jpn J Cancer Res 1985 Aug;76(8):699-704

32. Otsuki M; Saito H; Xu X; Sumitani S; Kouhara H; Kishimoto T; Kasayama S. Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells. Arterioscler Thromb Vasc Biol 2001 Feb;21(2):243-8.

33. Braunsberg HA; Coldham NG; Wong W. Hormonal therapies for breast cancer: can progestogens stimulate growth?. Cancer Lett 1986 Feb;30(2):213-8

34. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1995 Jan 18;273(3):199-208

35. News conference at the American Heart association Annual Meeting, Nov 17, 1994.

36. Hargrove JT, et al. menopausal hormone replacement therapy with continuous daily oral mircronized progesterone. Obstet Gyn 1989;73:606-12.

37. Hargrove, Osteen KG. An alternative method of hormone replacement therapy using the natural sex steroids. Infertile Repro Med Clinics north Am. 1995;6:563-674.DNH

38. Hargrove JT, Eisenberg E. Menopause. Med. Clinics North Am 1995;79:1337-1356.

39. Lemon Hm. Antimammary carcinogenic activity of 17-alpha-ethnyl estriol. Cancer 1987;60:2873-81.

40. Schneider J, Huh MM, Bradlow HL, Fishman J. (1984), Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells. J Biol Chem 259:4840-4845.

41. Vandewalle B, Lefebvre J. (1989), Opposite effects of estrogen and catechol estrogen on hormone-sensitive breast cancer cell growth and differentiation. Mol Cell Endocrinol 61:239-246.

42. Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. (1996), 2-hydroxyestrone: the ‘good’ estrogen. J Endocrinol 150:Suppl: S259-S265.

43. Fishman J, Martucci C. (1980), Biological properties of 16alpha-hydroxyestrone: Implications in estrogen physiology and pathophysiology. J Clin Endocrinol Metab 51:611-615. DNH

44. Schneider J, Kinne D, Fracchia A, Pierce V, Anderson KE, Bradlow HL, Fishman J. (1982), Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc Natl Acad Sci ,USA 79:3047-3051.DNH

45. Osborne MP, Bradlow HL, Wong GYC, Telang NT. (1993), Upregulation of estradiol C16 alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J Natl Cancer Inst 85:1917-1920.

46. Bradlow HL, Hershcopf RJ, Martucci CP,Fishman J. (1985), Estradiol 16a-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: A possible model for the hormonal etiology of breast cancer in humans. Proc Natl Acad Sci ,USA 82:6295-6299.

47. Telang NT, Suto A, Wong GY, Osborne MP, Bradlow HL. (1992), Induction by estrogen metabolite 16 alpha-hydroxyetrone of genotoxic damage and aberrant cell proliferation in mouse mammary epithelial cells in culture. J Natl Cancer Inst 82:634-638.

48. Kabat GC, Chang CJ, Sparano JA, Sepkovic DW, Hu XP, Khalil A, Rosenblatt R, Bradlow HL. (1997), Urinary estrogen metabolites and breast cancer: a case-control study. Cancer Epidemiol Biomark Prev 6: 505-509.

49. de Lignieres B. Oral micronized progesterone. Clin Ther 1999. jan;21(1):41-60.

50. Fitzpatrick LA, Good A. Micronized progesterone: clinical indications and comparison with current treatment. Fertil Steril 1999 Sept;72(3):389-97.

51. Adams MR; Register TC; Golden DL; Wagner JD; Williams JK Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis Arterioscler Thromb Vasc Biol 1997 Jan;17(1):217-21 (ISSN: 1079-5642

52. Wagner JD; Martino MA; Jayo MJ; Anthony MS; Clarkson TB; Cefalu WT. The effects of hormone replacement therapy on carbohydrate metabolism and cardiovascular risk factors in surgically postmenopausal cynomolgus monkeys. Metabolism 1996 Oct;45(10):1254-62

53. Levine RL; Chen SJ; Durand J; Chen YF; Oparil S. Medroxyprogesterone attenuates estrogen-mediated inhibition of neointima formation after balloon injury of the rat carotid artery. Circulation 1996 Nov 1;94(9):2221-7.

54. Register TC; Adams MR; Golden DL; Clarkson TB. Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys. Athrioscler Thromb Vasc Biol 1998 Jul;18(7):1164-71.

55. Pike MC, Ross RK. Progestins and menopause: epidemiological studies of risks of endometrial and breast cancers. Steroids 2000;65:659-64.

56. MacMahon B; Cole P; Brown JB; Aoki K; Lin TM; Morgan RW; Woo N. Oestrogen profiles of Asian and North American women. Lancet 1971 Oct 23;2(7730):900-2.

57. Lemon HM. Genetic predisposition to carcinoma of the breast: multiple human genotypes for estrogen 16 alpha hydroxylase activity in Caucasians. J Surg Oncol 1972;4(3):255-73

58. Lemon Hm. Oestriol and prevention of breast cancer. Lancet 1973;march 10:546-7.

59. Bulbrook RD; Swain MC; Wang DY; Hayward JL; Kumaoka S; Takatani O; Abe O; Utsunomiya J. Breast cancer in Britain and Japan: plasma oestradiol-17beta, oestrone and progesterone,and their urinary metabolites in normal British and Japanese women. Eur J Cancer 1976 Sep;12(9):725-35.

60.Speroff L. The breast as an endocrine target organ. Contemp Obst Gyn 1977 9:69-72. DNH

61. Adams MR et al. Inhibition of coronary artery athrosclerosis by 17-beta estradiol in ovariectomized monkeys: Lack of an effect of added progesterone. Arteriosclerosis 1990;10:1051-7.

62. Spellacy WN. A review of carbohydrate metabolism and the oral contraceptives. Am J Obstet Gynecol 1969 Jun 1;104(3):448-60.

63. Tikkanen MJ; Kuusi T; Nikkila EA; Sipinen S. Post-menopausal hormone replacement therapy: effects of progestogens on serum lipids and lipoproteins. A review. Maturitas 1986 Mar;8(1):7-17.

64.Newham HH. Oestrogens and atherosclerotic vascular disease: lipid factors. Baillieres Clin Endo Metab 1993;7:61-93.

65. Lobo RA. The role of progestins in hormone replacement therapy. Am J Obstet Gynecol 1992 Jun;166(6 Pt 2):1997-2004

66. Bolaji II; Grimes H; Mortimer G; Tallon DF; Fottrell PF; O'Dwyer EM. Low-dose progesterone therapy in oestrogenised postmenopausal women: effects on plasma lipids, lipoproteins and liver function parameters. Eur J Obstet Gynecol Reprod Biol 1993 Jan;48(1):61-8.

67. Moorjani S; Dupont A; Labrie F; De Lignieres B; Cusan L; Dupont P; Mailloux J; Lupien PJ. Changes in plasma lipoprotein and apolipoprotein composition in relation to oral versus percutaneous administration of estrogen alone or in cyclic association with utrogestan in menopausal women. J Clin Endocrinol Metab 1991 Aug;73(2):373-9.

68. Minshall RD; Miyagawa K; Chadwick CC; Novy MJ; Hermsmeyer K. In vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones. FASEB J 1998 Oct;12(13):1419-29

69. Minshall RD; Stanczyk FZ; Miyagawa K; Uchida B; Axthelm M; Novy M; Hermsmeyer K. Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J Clin Endocrinol Metab 1998 Feb;83(2):649-59.

70. Fahraeus L; Larsson-Cohn U; Wallentin L. L-norgestrel and progesterone have different influences on plasma lipoproteins. Eur J Clin Invest 1983 Dec;13(6):447-53.

71. Jensen J; Riis BJ; Strom V; Nilas L; Christiansen C. Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women. Am J Obstet Gynecol 1987 Jan;156(1):66-71.

72. Ottosson UB; Johansson BG; von Schoultz B. Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone. Am J Obstet Gynecol 1985 Mar 15;151(6):746-50.

73. Elkind-Hirsch KE; Sherman LD; Malinak R. Hormone replacement therapy alters insulin sensitivity in young women with premature ovarian failure. J Clin Endocrinol Metab 1993 Feb;76(2):472-5.

74. Bush TL; Barrett-Connor E; Cowan LD; Criqui MH; Wallace RB; Suchindran CM; Tyroler HA; Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987 Jun;75(6):1102-9.

75. Godsland IF; Gangar K; Walton C; Cust MP; Whitehead MI; Wynn V; Stevenson JC. Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy. Metabolism 1993 Jul;42(7):846-53.

76. Morey AK; Pedram A; Razandi M; Prins BA; Hu RM; Biesiada E; Levin ER. Estrogen and progesterone inhibit vascular smooth muscle proliferation. Endocrinology 1997 Aug;138(8):3330-9.

77. Lee WS; Harder JA; Yoshizumi M; Lee ME; Haber E. Progesterone inhibits arterial smooth muscle cell proliferation. Nat Med 1997 Sep;3(9):1005-8.

78.Colditz GA; Hankinson SE; Hunter DJ; Willett WC; Manson JE; Stampfer MJ; Hennekens C; Rosner B; Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995 Jun 15;332(24):1589-93.

79. Von Schoultz B; Soderqvist G; Cline M; von Schoultz E; Skoog L Hormonal regulation of the normal breast Maturitas 1996 May;23 Suppl:S23-5.

80. Chen Y; Liu X; Pisha E; Constantinou AI; Hua Y; Shen L; van Breemen RB; Elguindi EC; Blond SY; Zhang F; Bolton JL. A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines. Chem Res Toxicol 2000 May;13(5):342-50

81. Desreux J; Kebers F; Noel A; Francart D; Van Cauwenberge H; Heinen V; Thomas JL; Bernard AM; Paris J; Delansorne R; Foidart JM. Progesterone receptor activation. an alternative to SERMs in breast cancer. Eur J Cancer 2000 Sep;36 Suppl 4:S90-1






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