"He who laughs...
-      -Mary Poole

The Way Up Newsletter
Vol. 34, 09-08-02



Let's examine the recent Women’s Health Initiative (WHI) study which almost created hysteria.
Who knows how many frightened women stopped taking any kind of hormone therapy upon hearing the widely publicized findings regarding Prempro increasing the risk of breast cancer verses those on placebo.
What the media did not make clear, is that the part of the study which was prematurely discontinued because of breast cancer risk was only the group taking Prempro, a combination of Premarin & synthetic progestin. The 10,734 women in a separate trial who are only taking Premarin, did not exhibit the same risk as the combination group & these women are expected to continue Premarin for the originally scheduled 8.5 years. However, all women in the Premarin only trial had had a hysterectomy so they likely had lower levels of hormones . We would then expect less problems from excess hormone effects. In the year 2000, there were 46 million prescriptions written in the US for Premarin.
I’m no fan of Premarin ( a horse urine derived estrogen), but am definitely opposed to the use of synthetic progesterone (called progestins) . For more about this as a background for the rest of this newsletter, be sure to see my May 15, 2000 input on the subject of hormone replacement. We will be building upon, rather than repeating what is there, so it is necessary as a background.
Any responsible alternatively oriented Dr would not prescribe Prempro. Unfortunately, the researchers chose hormones which are not chemically identical to what you produce in your body & are likely to metabolize differently. Those practicing a more natural form of medicine prescribe compounded hormones derived from soy & wild yam which are chemically identical to what your body makes. So the combination used in the study was problematic. Yet since there were 22.3 million prescriptions written for Prempro in the US in the year 2000, we can make a case for studying what is widely used (though I call it misused).
As if the hormone choice for the study were not bad enough, there were no screening tests to see who had low hormone levels, together with symptoms of hormone deficiency. It is likely some of the 8,506 women chosen to receive Prempro did not need these hormones & taking Prempro would create excessive levels.
The criteria for who might need hormones & for inclusion in the study was no vaginal bleeding for 6 months ( 12 months for 50-54 year olds), or a history of a hysterectomy, or previous use of postmenopausal hormones. Naturally, women with previous breast or other cancer within the last 10 years were excluded.
I do not consider this proper criteria. The absence of vaginal bleeding does not automatically mean the hormone levels are low enough to produce symptoms, or possibly speed the aging process. I have tested women in their 80’s who had serum estradiol levels between 200-300 who had never taken any hormones! Usually there will be significant estrogen deficiency symptoms at levels under 30, & the level I am looking to achieve with HRT is 75-100.
How many of the 8,506 women put on Prempro had adequate hormone levels to begin with? And how many of these were the ones who had problems from the Prempro? We’ll never know. How can you replace something natural to the body, but possibly declining without having baseline levels proving a need & follow up levels for dosage guidance? All these women were put on the same dose which again is all too common a practice.
8,506 women received Prempro, while 8,102 took a placebo. The study was supposed to be double blinded meaning neither the Dr nor the patient knows who is getting which.
However, during the study 40.5% of those receiving Prempro became unblinded because the Dr’s had to deal with persistent vaginal bleeding. This alone tells me the dose was too high , it was the wrong combination, or these women shouldn’t have been taking hormones at all. With correct natural hormone dosing, there should be no vaginal bleeding! What we also don’t know is how many of these 40.5% were the ones with the other side effect problems.
Remember, I would not prescribe Prempro, but lets look at reality, at the actual figures creating such a media sensation, as I’m surprised the Prempro & sloppy study criteria didn’t cause more problems.
For the 5.2 years the study lasted, counting all of the excess events, one more in every 100 women receiving Prempro verses placebo had a significant side effect , which means 100 problems per 10,000 women.
Statistically extrapolated, for those on Prempro verses placebo, per 10,000 women taking the drug for a year there were:
• 8 more cases of breast cancer (with the risk beginning after 3 years of hormone use ). However, this translates into 8,000 more cases per 10 million users, so it starts looking a bit more ominous.
• 7 more cases of cardiovascular events
• 8 more cases of pulmonary embolism
• 6 fewer cases of colon cancer
• 5 fewer cases of hip fracture (guess they didn’t count other broken bones)
"The number of overall deaths in the treatment group verses the placebo group were statistically & clinically similar in this short duration study"
The conclusions were , "The absolute risk of harm to an individual woman is very small." and "The results do not necessarily apply to lower dosages of these drugs, to other formulations of oral estrogens, & progestins, or to estrogens & progestins administered through the transdermal route. It remains possible that transdermal estradiol with progesterone which more closely mimics the normal physiology & metabolism of endogenous sex hormones, may provide a different risk benefit profile" I’ll give them credit for that.
And elsewhere, "It is always necessary to weigh the possibility of small absolute risks against the severity of menopausal symptoms & the possible benefits of treatment".
Their criticism was of the tendency by some to expect Prempro to prevent a variety of chronic diseases, which they felt was refuted by the study. I don’t feel the study told us much of anything we shouldn’t have known. The question should be can chronic disease states be prevented in those who have proven measured hormone deficiency by using individualized & correct natural HRT?
To date HRT is only FDA approved for the relief of menopausal symptoms & the prevention & treatment of osteoporosis.
This decision can be made by assessing how many hormone deficiency symptoms you have , & actually measuring your hormones in your blood or urine. Also , consider your lifestyle & genetic risks for breast cancer. When you qualify, the dose must be individualized according to your test results, to give the minimum HRT which restores a feeling of well being. The dose should be adjusted as indicated by symptoms & follow up testing.
Since my last newsletter on this topic 2 years ago, more tests have become available.
My current preference is 24 hour urinary hormone testing. Generally I use Antibody Assay Lab and type "6450" in the search box . This includes all three forms of estrogen (Estrone, Estradiol, Estriol) , thyroid, progesterone, testosterone, DHEA, pregnenolone, cortisol, & other adrenal hormones, hormone metabolites. & some minerals. The blood tests mentioned in my other newsletter are still good. Also, Great Smokies Diagnostic Lab has a serum hormone panel which is all inclusive.
If you start HRT, follow up testing should be done every 6 months-2 years depending upon how well you are doing.
Both of these labs have tests for estrogen metabolism, as well. You’ll see the importance of knowing how you are metabolizing estrogen as you read further.
You can ask your Dr to order these tests, or if resistant, you can contact the lab for a referral to a Dr in your area who uses these tests & natural hormone replacement.
Most women on HRT are only on the Estradiol (E2) form of estrogen. Our body also produces Estrone (E1) & Estriol (E3). Research has shown that those women with a 2/1 ratio or greater of Estriol verses Estradiol have a lower risk of breast cancer. Conversely those with a lower ratio have a higher risk of breast cancer. When the different estrogens are measured the prescription can be written with an E3/E2 ratio to maintain or correct the ratio shown on the tests. I will generally give at least 2 times more E3 than E2. With compounding there can be a precise individualization of dose not possible with already made products & the important cancer decreasing Estriol can be included.
Some of the non compounded forms of Estradiol (E2) on the market which are at least naturally derived from soy or yam, are: Estrace, Ortho-Est, Ogen, Estraderm, Vivelle, Alora, Climara, & Fempatch, & Cenestin. But they are in fixed doses & do not contain any E3.
When taking Progesterone, it must be the natural, not the synthetic form. Either Prometrium found at most pharmacies or a compounded product. It must always be taken when taking Estrogen, but you can take Progesterone without taking any Estrogen & it alone may suffice for some women. For all you might want to know about Natural Progesterone, I refer you to the web site of the world authority on the subject Dr John Lee.
When there is a need to add testosterone it should be used as a skin cream or gel, not in the pill form as in the popular oral Estratest (estrogen/testosterone combo) The oral form of testosterone confers a very slight increased risk of liver cancer which does not happen with the cream or gel which bypasses the liver.. When absent or low sex drive/response is an issue the cream can be compounded for application to the clitoral/vulva area to aid sexual response.
One may also use what are called precursor hormones which the body can convert to estrogen, progesterone, & testosterone as needed.
These are: DHEA or Pregnenolone .
This is the most conservative HRT approach & is sometimes enough if the hormone levels are mildly depleted with milder symptoms. Their safety is attested by extensive studied, by their being available over the counter, widely used & misused & there still being no cause to remove them from circulation (despite the desire by some to find such cause).
If you have a history of breast, uterine, or ovarian cancer, venous thromboembolism, gallbladder disease, or cardiovascular disease you would need other options or to proceed carefully after further evaluation of risks. However, some of the same risk factors may not apply to certain of the compounded hormones.
We may assume that many women who experience heart attacks, strokes, blood clots or breast cancer after undergoing HRT are already predisposed to these conditions through genetic or lifestyle factors. . Where this is a concern one can now have genetic testing to ascertain risk factors for these conditions & find out what natural steps can be taken to modify such risk. If considered high risk, one would ideally do all 4 genetic tests listed. All tests can be performed on one saliva sample collected at home & mailed in a kit to the lab. This testing can reveal genetic risk for heart disease, excessive blood clotting, a tendency to cancer, or osteoporosis & what you can do to minimize the risk & be able to more safely use HRT, if needed..
Certain factors increase estrogen in the body & were not accounted for in the study in question. With obesity there is increased production of estrogen by fatty tissue. Alcohol consumption increases estrogen levels & studies have shown moderate alcohol consumption increases the risk of breast cancer.
Evidence is steadily accumulating that it is not the estrogen, but how estrogen is metabolized in the liver that determines whether or not it creates a cancer risk. There are 3 major breakdown products of estrogen metabolism: 2-hydroxyestrone (2-OH) which is a "good" estrogen with low cancer risk; 16-alpha-hydroxyestrone (16-alpha-OH), & 4-hydroxyestrone (4-OH) which are "bad" with persistent estrogenic activity which promotes tissue proliferation & cancer. There is some belief the good 2-OH may even inhibit cell proliferation & help prevent cancer.
In a recent 5 year study of 10,786 women it was found that premenopausal women who developed breast cancer had a decreased 2-OH to 16-alpha-OH ratio & a higher percentage of 16-alpha-OH than 2-OH. Those women who primarily metabolized estrogen to 2-OH were 40% less likely to have developed breast cancer during the 5 years.
Another case control study in post menopausal women found those who developed breast cancer had a 15% lower 2-OH/16-alpha-OH ratio than control subjects & those with the highest 2-OH/16-alpha-OH ratio had a 30% lower risk for breast cancer. Factors which adversely affect this ratio are pesticides, drugs such as Tagamet (cimetidine) obesity, genetic predisposition, & a deficiency of the nutrients or other substances which favorably affect the ratio of these metabolites.
Cancer protective beneficial improvement in estrogen metabolism can be accomplished by increasing dietary fiber, reducing fat, losing weight (if overweight), & increasing exercise.
Certain dietary supplements also encourage the preferred pathways of estrogen metabolism. These are the B vitamins (especially folic acid), Magnesium, Selenium, Vitamins A, E, C , flavonoids, lignans (as found in whole flax seed), cruciferous vegetables (broccoli, cauliflower, brussell sprouts)-also available as the supplement indole-3-carbinol, isoflavones as in soy or kudzu, omega 3 fatty acids as in fish or fish oils, green tea, curcumin, N-acetyl-cysteine, alpha lipoic acid, lycopenes, calcium-D-glucarate, acidophilus, & bifidus.
Melatonin, co-enzyme Q10, & conjugated linoleic acid (CLA) have also been found to have breast cancer protective effects.
You can make these life style adjustments & take the supplements, or you can first test for how you are metabolizing estrogen & just take the needed supplements to improve your metabolism if there is a problem.
You can then follow the lifestyle modification recommendations & use phytoestrogens such as the isoflavones found in soy, & the lignans in whole flaxseed & use vitamin E. Phytoestrogens appear to be both estrogenic & anti-estrogenic. They can bind to estrogen receptor sites, increase plasma Sex Binding Globulin( making less of the harmful free estrogen available), decrease aromatase activity(which improves estrogen metabolism) , & alter estrogen metabolism to produce more of the good 2-OH & less of the bad 16-alpha-OH.
You may use various herbal supplements such as Remifemin.
Whether on HRT or not all women should have a PAP test & mammogram every 1-2 years
This months relevant nutrients are:
Green Tea plus Magic Fruit


Hopefully this has answered some of your questions about HRT.
Peace & Health,
Priscilla Slagle M.D.



One evening an old Cherokee told his grandson about a battle that was going on inside himself. He said, "My son, it is between 2 wolves......
One is evil: anger, envy, sorrow, regret, greed, arrogance, self-pity, guilt, resentment, inferiority, lies, false pride, superiority & ego....
The other is good: Joy, peace, hope, serenity, humility, kindness, benevolence, empathy, generosity, truth, compassion, & faith."
The grandson asked, "Which wolf wins?"
The old man simply replied, "The one I feed."
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