A Wake-up Call
The recent discontinuation of the Women's Health Initiative Hormone Replacement Trial, sponsored by the National Institute of Health (NIH), served as a loud wake-up call to the doctors who have been routinely prescribing the conventional HRT (containing synthetic hormones) despite the fact that safer bio-identical hormones have been known for years. The information you are about to read represents the search and struggle I went through to find the safe and effective hormone replacement that makes sense for my own health.

Let's get it straight
A healthy young woman's body produces both progesterone and estrogen in balanced amounts. Are they at a higher risk of coronary artery disease, cancer, stroke, blood clot, dementia, etc. like the women given the non-human, synthetic fake hormone combination? Absolutely not!

Why do we need to supplement hormones?
At menopause the hormones produced primarily in ovaries (progesterone and estradiol) drop dramatically and this drop causes serious health problems in addition to unpleasant menopausal symptoms. Restoring hormone balance will promote general health and reduce the risks of cancer, coronary artery disease, stroke, blood clot, dementia, and bone loss.

Note: The levels of other two main human estrogens Estrone and Estriol do not go down at menopause. Post-menopausal plasma estrone level stays the same as the early follicular phase (the low estrogen phase) level (Nichols et al, O. G. Survey 39:231,1984). In fact, after menopause both the estrone and estriol levels may increase slightly compared to the early follicular phase levels according to some saliva test data. This is because estrone is the primary estrogen the body tissues make, and estriol is a metabolite of estrone and estradiol, which eventually goes out of body in urine, sweat and stool.

Safe natural HRT that makes sense
Step 1. natural progesterone cream 1/8 to 1/4 tsp once or twice per day
The aim is to supplement 10 to 40 mg of progesterone a day. During perimenopause and early post menopause period, this may be the only hormone supplementation you need to balance your hormones, because your body still produces enough estrogen.
Please note: Your menopausal symptoms such as hot flashes, night sweats, etc. are not directly related to your estrogen or progesterone levels, although supplementing either or both is well known to reduce or eliminate the symptoms, the mechanism is not at all understood at this point. Low blood sugar level, or the mechanism to raise blood sugar level when it becomes low is emerging as the more direct trigger of hot flashes in recent studies (hot flashes do not occur after a meal for about 90 minutes: see Menopausal hot flash frequency changes in response to experimental manipulation of blood glucose. Sharon L Dormire, Nancy King Reame 2003). Also, factors known to compromise your cardiovascular health (especially, smoking, prolonged stress, and less physically active) also increase the severity of the symptoms. Also, menopausal symptoms share many features with other withdrawal symptoms (Benzodiazepine, morphine, etc.), but their mechanism is not well understood, either. For research reviews, see Menopausal Symptoms And Underlying Mechanism and Menopausal Symptoms And Cardiovascular Health
Important: If you are already on estrogen, quitting cold turkey is not a good idea. It is best to avoid severe menopausal symptoms or you will risk rapid bone loss due to the high stress hormones that accompany. See Menopausal and What Really Happens to your Bones. Remember estradiol patch is 10 times more effective than oral estrogens. So if you were on 0.65mg Premarin, 0.05mg/day estradiol patch is equivalent. If estradiol 0.05mg/day transdermal brings back the symptoms, you can try 0.075mg or double up 0.05mg patches, then after 3 to 4 months try 0.05 again. Many women with intact ovaries find 0.025mg estradiol patch satisfactory.
Important: Even if you do not have any menopausal symptoms, you must supplement natural progesterone to avoid estrogen dominance which can lead to coronary artery disease, cancer, stroke, blood clot, etc. and also to protect your bones and brain and for a host of other physiological benefits progesterone alone can provide. You are most likely to benefit from natural progesterone cream many years before the onset of actual menopause symptoms. See Estrogen dominance: it's not just a theory for more on estrogen dominance.

Step 2. DHEA, plant estrogens /herbs
If natural progesterone cream alone does not take care of your menopausal symptoms, and the symptoms are mild, adding DHEA 5 to 30 mg a day will take care of them. DHEA will turn into testosterone and estrogen in various tissues of your body where they are needed, reduces stress hormone cortisol, reduces insulin resistance, and can protect your bones. Only problem is that it takes 3 months to kick in. Recent studies indicate low DHEA level may prolong the symptomatic period. DHEA may also help you and your partner's libido, but neither of you should ever take it without progesterone. It can raise cancer risk for both of you.
Some plant estrogens and herbs may also help. Isoflavones, Don Quai, Black Cohosh, Red Clover, etc. are well known for their effects. You can also take fermented soy products such as tempe, natto, and miso instead of soy Isoflavones. The fermentation makes the plant estrogens in soy more bio-available. Also fermentation eliminates harmful oxalic acid in soy. However, soy isoflavones genistein and daidzein are known to interfere with thyroid hormone synthesis and should be taken in moderation with enough iodine.

Step 3. estradiol skin patch
For menopausal symptoms (hot flashes, night sweats, palpitations, etc.) ultra low does of estradiol (0.025 to 0.050mg) is highly effective and safe when combined with real natural progesterone. Supplementing natural progesterone + DHEA, plant estrogen /herbs may not be enough. Also remember it is not the absolute level of estrogen, but rather it may be the lose of sensitivity to estrogen that determines the severity of the symptoms. In other words, it is a form of addiction resulted from prolonged severe estrogen dominance. Transdermal estradiol is safe when combined with natural progesterone as shown in a large French study series (see Safe Use of Hormones: the Hard Evidence for a review). If you use low dose estradiol and progesterone for the same duration (25-27 days continuous) every month, uterine lining will not thicken and no bleeding will occur except some spotting at the beginning (see Hormones: Dos and Don'ts for a review).

Important: Although estradiol supplementation alone may seem sufficient to get rid of all the menopausal symptoms (that is what your doctor would tell you if you do not have uterus, and if your doctor is an average doctor like mine was.), you must supplement natural progesterone even if you do not have uterus to avoid estrogen dominance which can lead to coronary artery disease, cancer, stroke, blood clot, etc. and also to protect your bones and brain and for a host of other physiological benefits progesterone alone can provide. You are most likely to benefit from natural progesterone cream many years before the onset of actual menopausal symptoms (see Hormonal Balance And Women's Health for detail).

Why natural progesterone cream?

• Natural progesterone is the only safe and effective choice. It is manufactured by converting a plant oil called diosgenin extracted from soy and wild yam, and it is bio-identical to human progesterone. Stay a way from all other synthetic progestins such as levonorgestrel, medroxyprogesterone acetate (Provera), norethindrone acetate, etc. They are not bio-identical to human progesterone, therefore very dangerous as demonstrated clearly by the PremPro clinical trial.
• I prefer natural progesterone cream manufactured by supplement companies because their standard dosage and the delivery medium are well researched and established compared to the physician prescribed compounding pharmacy preparations. I also like the convenience of buying it without doctor's prescription.

  Note:Natural progesterone (in cream or oil form) is one of the safe hormones that are sold as supplements in the U.S. High dose micronized progesterone in gel caps (Prometrium 100mg, 200mg) and suppository (Crinon 45mg, 90mg) are also available as prescription drugs, however, they are too high for hormone balancing purposes. If you are going to ask your doctor to prescribe progesterone cream from a compounding pharmacy, make sure your daily dosage will be 10 to 40mg.The de facto standard is 500mg of progesterone in 30g of cream. Natural progesterone has calming effects and you will feel calm and well with the right amount, however, you may feel sleepy, sluggish, and even depressed if you get too much. The right amount may differ depending on your conditions and you may need to adjust based on how you feel. Although progesterone overdose is not as dangerous as estrogen overdone, it can mess up Calcium/Magnesium metabolism, which affect your bone and water retention.

  Important: Don't let your doctor over dose you. Doctors are brain washed to think 1) Most of oral progesterone gets "digested", therefore it requires 10 times more than what you actually need. 2) progesterone does not get absorbed much through skin, therefore it requires 10 times more than what you actually need. Both are myth, only half true at best. One time I consulted a doctor who seemed better informed. When I asked him about oral progesterone, he prescribed me 100mg capsules. It made me so tired and lethargic I had to quit after 2 days.

  Important: Don't let your hormone test misguide you. One of the reasons many doctors still believe natural progesterone no good is that it does not show up in a regular blood test. Doctors are brain washed to think: your blood hormone level (98% inactive, 2 % active form of hormone) has to achieve the same level as normal reproductive age level by supplementing active form of hormone (micronized powder in gel cap or liquid in cream, oil, gel, patch, spray, etc.), and measuring inactive form of hormones. Although what really matters is the level of active form of hormones and the traditional blood test is not sensitive enough to keep track the active form of hormones. If you want to see how much your body has absorbed, use saliva test or blood spot test, which reflect the amount of supplemented hormones delivered to the tissues, but go through a rapid rise and fall within a span of half a day. For most people, the symptoms, how you feel is a good enough measure, if not better. There seams to be a wide individual differences.

• Estradiol is the most potent estrogen among the three human estrogens (estradiol, estrone, estriol), therefore requires the least amount in correcting a wide range of menopausal symptoms, which occur due to the drop in estradiol and progesterone levels to begin with.
• Skin patch is better than pill because it requires 1/10 of pill (for example: 0.3 mg /day by pill compared to 0.03 mg /day by patch, according to the standard dosage set by the manufacturers) to get the same benefits. My common sense tells me less is better when it comes to hormone supplementation. Your body has to process less and that means less work for the liver and kidneys and less hormone byproducts that are health hazard.
• Skin patch provides a low and steady amount of estradiol continuously to recreate the active estrogen pattern seen in the low estrogen phase of premenopausal body. One patch lasts for 4 days (7 days for some brand). Other transdermal forms (cream, gel, or drop) may allow easier adjustment, but cannot provide steady continuous delivery. You can reduce patch dosage by temporally removing it until the unpleasant overdose symptoms go away or cutting or trimming the patch, increase by putting more patches.
• The standard dosage and the delivery medium of prescription estradiol skin patches manufactured by pharmaceutical companies are well researched and established compared to the physician prescribed compounding pharmacy preparations in cream, gel, drop, or gel cap forms. (* A compounding pharmacist told me she cannot make one month supply of 0.03mg/day estradiol preparations because the measuring device does not allow the accuracy at that level, and she cannot guarantee the potency beyond one month.)

Why not pill or gel cap?

1. For both estrogen and progesterone, transdermal application (patch, cream, oil drop, spray, or gel) allows you to adjust the dosage. This is especially important at the beginning when you are not certain about the dosage. You may have to gradually increase or decrease the dosage depending on your situation.
   
2. Because of the way hormones are processed in the digestive system, pills and even the micronized hormones in gel caps have well known health risks: gallbladder disease due to thickened bite, and high blood pressure due to increased production of the enzymes renin and angiotensin in the kidneys.
   
3. When estradiol goes through the digestive system and the liver, most of it is converted to estrone which is less potent than estradiol for the menopausal symptoms AND just as dangerous for the breast cancer.
   
4. Oral estrogen supplementation is well known for its effects in raising blood clot risk factors.
   

How about other forms of estrogens?
Estradiol is the only estrogen available in patch form, however, there are many prescription estrogens that contains estradiol, estrone, estriol or their synthetic (or equine in case of Premarin) equivalents in pill, gel, cream, subcutaneous implant, virginal suppository, or virginal ring forms. Even if you limit your choices to natural (=bio-identical to human's) estrogens as opposed to the fake (synthetics), equine, or plant varieties, you will still find a confusing array of choices depending on who you ask.

• Compounding pharmacists offer tri-est (80% estriol, 10% estradiol, 10% estrone) or bi-est (20% estradiol and 80% estriol) claiming this is the ratio that is seen in a menopause woman's body. However, I could not confirm this claim anywhere.

  According to some saliva test data estriol is the dominant estrogen in pregnancy, otherwise, the estriol level may be slightly higher than estrone, but not 8 times like compounding pharmacists claim. I suspect the 80% estriol myth was created when the importance of natural progesterone was not known and estriol (the weakest estrogen) was promoted as the only HRT that did not pose cancer risks. If you are going through a treatment for a hormone positive cancer, estriol + natural progesterone (both are anti-cancer) can be your choice of hormone supplementation.
  Note: I tried transdermal (drop) tri-est 0.3mg/day prescribed by my doctor, and ended up throwing it away because it caused headaches, fatigue, and muscle weakness. I suspect the dose was too high and it takes time for the body to get used to it.

• Some physicians offer long lasting (6 month) subcutaneous (under the skin) implant or virginal rings that requires a physician to administer and monitor in addition to writing prescriptions. You cannot control the dosage of these forms of application and they tend to be irritating. In general it is best to avoid them.

The Conventional HRT - PremPro - Clinical Trial Facts
The arm of the study that was stopped involved the testing of PremPro (Premarin plus Provera) in menopausal women with an intact uterus. The study lasted 5.2 years and was stopped because the data demonstrated a clear-cut disadvantage in the Prempro group versus the placebo group.

The data showed that after 5.2 years "hazard ratio" for the following reached to the point where it was too risky to continue.

Coronary artery disease 1.29:1 (29% increase)
Breast Cancer 1.26:1 (26% increase)
Stroke 1.41:1 (41% increase)
Pulmonary embolus (blood clot to the lung, a complication of deep vein thrombosis) 2.13:1 (113% increase)

Important thing to note here is that these risks are part of estrogen dominance effects, which are intensified by Provera (synthetic progestin). When you use estrogen alone (standard for those without uterus), these estrogen dominance effects increase slower. That was the reason the Premarin alone clinical trial was not discontinued until March of 2004 although it was clear the risks were there, the "hazard ratio" did not reach to the pre-set criteria for discontinuation. Personally I think it is unethical to have continued Premarin alone trial as long as they did while the risks are clearly shown in a year 2000 report (see JAMA 283 (2000) report by Schairer C, et al.) and safer alternatives are known.

There was a decrease in the risk of hip fracture with HRT (34%), a decrease in the risk of colorectal cancer (37%), and a decrease in the risk of endometrial (uterine) cancer (17%). Important thing to note here is that these benefits can be achieved by using natural estrogen and progesterone combination without the risks associated with synthetic hormone (PremPro) use. In France, researchers found transdermal estradiol + progesterone (natural) combination safe and effective. See Safe Use of Hormones: the Hard Evidence and Hormones: Dos and Don'tsfor more.

What your doctor may tell you about natural progesterone

Here is the official position of The North American Menopause Society
"In the absence of clinical trial data from each estrogen and progestogen, the clinical trial results for one agent probably should be generalized to all agents within the same family, especially with regard to adverse effects." (from NAMS HT Position Statement, published September 2003)

Is this "the most up-to-date and scientifically based recommendations currently available on the clinical use of ET/EPT in peri- and postmenopause." like the NAMS doctors claim? I sure don't think so. You can judge it for yourself by checking the real scientific research listed in the following books and in my blog Hormone Research Review. The above statement probably should be interpreted as legally based recommendations intended to protect the doctors and pharmaceutical companies.

Recently I have learned that some people went back and "reanalyzed" the Women's Health Initiative Hormone Replacement Trial by excluding "high risk older women" to demonstrate that both estrogen alone and Prem-Pro are safe if you limit the age and the length of use. I don't know why they waisted their time and efforts in that kind of futile exercise. It took 5 years to reach the preset statistical hazard ratio, but there were people who became sick in less than one year, and they developed more severe symptoms than non user cancer victims. "...the WHI study found that, among 10,000 women taking estrogen plus progestin for one year, there will be 8 more cases of breast cancer among the hormone users than if they had not taken the therapy"is what the researchers said. So, it is only as safe as Russian roulette, I would say.

Books/Links

• My blog on Hormone Research
  
• PremproCounsel Legal Team
  
• Virginia Hopkins Health Watch
  
• Hormone Balance; a Matter of Life and Health by Kristine B. Klitzke, R.N. 2002, Sound Concepts, Inc.
  
• What Your Doctor May Not Tell You About Breast Cancer, by John R. Lee, M.D. David Zava, Ph.D, and Virginia Hopkins, 2002 Warner Books.
  
• What Your Doctor May Not Tell You About Menopause, by John R. Lee, M.D. with Virginia Hopkins, 1996, Warner Books.
  
• What Your Doctor May Not Tell You About PreMenopause, by John R. Lee, M.D. Jesse Hanley, M.D., and Virginia Hopkins, 1999, Warner Books.
  
• Progesterone in Orthomolecular Medicine by Raymond Peat, PhD, available at Dr. Ray Peat's Web site.