Natural Hormone Therapy
Frederick R. Jelovsek MD
"I'm looking for information on estrogen replacement. I'm 43, and menopause is complete. I'm currently taking triestrogen and progesterone. I would prefer a more natural method of replacement. ". D
It sounds as if you are already on what most women would call "natural" hormone replacement. Triest is a combination of three types of estrogens: estriol, estradiol and estrone. The compound called estriol is a weak estrogen that naturally occurs in women. It occurs in fairly high blood levels in pregnancy but is very low in amount at any other time. Progesterone is also naturally produced by premenopausal women but almost exclusively in the last two weeks of the menstrual cycle. Both of these compounds occur naturally in women but both are made synthetically by a patented chemical process usually from a plant steroid compound as a chemical precursor.
Why Natural
It would be nice to know what it is about the term "natural" that makes it sound appealing. Is it:
- occurring in nature and not made by a chemical process that might introduce impurities that have unexpected effects?
- the same chemical compound(s) that naturally occur in women before the menopause?
- hormones that are safe from contamination from animals?
- hormones that are safe from herbicide and pesticide contamination?
- hormones that have been very thoroughly studied so that their benefits and side effects are well known with no unexpected long term adverse consequences?
- hormones that are natural would not be very likely to be associated with an increased breast cancer incidence?
As you may suspect, there are no compounds that meet all of these criteria. In fact only a few substances meet even 3 of the above 5 conditions.
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What are natural estrogens?
Estrogens and other reproductive hormones that occur naturally in women are:
- estrone
- estradiol
- estriol
- progesterone
- testosterone
None of the above naturally occur in plants or in animal products. They all need to be manufactured by a chemical process. They are currently manufactured from yam or soy precursor steroid molecules. A patented chemical process is used to make them into the same chemical structure as is found in women.
These hormones are then made into very small clusters of molecules called micronization. Micronized hormones are better absorbed in the stomach. If they were not micronized, they would probably be ineffective due to poor absorption.
It is very important to understand that these hormones are not more or less likely than other prescription estrogens to produce a slightly increased incidence of breast cancer. In fact estradiol used in Europe has been associated with increased breast cancer incidence just as conjugated estrogens in the U.S.
Other estrogens such as plant estrogens may also be considered by some to be "natural". Since animals are also natural, I think you can make a good case that conjugated estrogens such as Premarin® are also natural.
Are phytoestrogens (plant estrogens) better to take than regular estrogens by prescription?
Phytoestrogens have not been studied as well as other estrogens, especially conjugated estrogens. They have many effects similar to synthetic or manufactured natural estrogens but some effects are less or different. Phytoestrogens can reduce hot flashes although not as well as regular estrogens. They also have some effect on coronary artery disease although they do not improve lipids as well as estrogens. Finally, soy phytoestrogens and probably other phytoestrogens do not improve vaginal dryness at all. As far as effect on breast cancer, we do not have any data yet. Women who have diets high in phytoestrogen have lower incidences of breast cancer but there are very many other dietary and living differences in those groups of women. So it would be wrong to conclude at this time that phytoestrogens have any protective effect against breast cancer or even to rule out that they may increase breast cancer as do other estrogens. The bottom-line with phytoestrogens at this time is that they have some, but not all, the beneficial effects of estrogens. There are some over-the-counter non prescription phytoestrogens available.
Which are the best estrogens to take to minimize the chances of breast cancer?
It bears repeating that there is no scientific evidence that any of the estrogen products -- natural estradiol, estriol, estrone, conjugated estrogens (Premarin®) including phytoestrogens taken in a concentrated, non dietary form, i.e., a pill, -- has a lower incidence than any other. In fact it is very likely that all of the products have a dose and time related promotion of breast cancer. Even soy-based phytoestrogens, which most doctors and nutritionists would like to think might be safer, have been shown to increase breast ductal cell proliferation in women. Less than five years of use does not seem to have an increased risk whereas greater than 15 years of use is associated with an increased breast cancer risk in all studies. As doses are higher, there seems to be a higher risk.
The best strategy for women on estrogens with regard to breast cancer is:
- do not skip any regularly (usually annually) scheduled mammograms
- as you get further past menopause, gradually decrease the dose of estrogens.
For example, women close to menopause (under 55-58) may need to take 1.25 conjugated estrogen equivalent. Then up to age 65, use 0.625 equivalent. And finally from 65 to 75 go to a 0.3 mg conjugated estrogens equivalent which will continue to protect against osteoporosis.
Now you ask, how did rumors get started that estriol was a "safe" estrogen and estrone and estradiol were "bad" estrogens? Basically there are no long term studies using estriol and there are not likely to be any in the next few years. The studies showing a slightly increased breast cancer incidence used predominantly estrone (in conjugated estrogens) and estradiol (in European studies). Therefore estriol did not show the same increased cancer incidence but only because it had not been used very much for hormone replacement and therefore it was not studied. Only non-scientific thinkers would conclude it was safer.
Which estrogens have the least side effects?
The major side effects of estrogens are bleeding problems, while the longer term complications are uterine cancer (endometrial), if progestins/progesterone is not given concurrently, and breast cancer. Remember that they are protective against colon cancer, heart disease, Alzheimer's disease and osteoporosis. If progestin/progesterone is given along with estrogens in women with a uterus, they can have more side effects, especially mood side effects and that is a major reason for discontinuing replacement therapy.
The bleeding complications occur only in women who still have a uterus and there is a least a 20% incidence of annoying bleeding problems that leads to discontinuance. However, none of the estrogen products seem to have less bleeding problems than others. All of them need progestin/progesterone to counteract the bleeding and most of the problems that doctors have in regulating bleeding problems are dose related, not type of estrogen related.
Progestins seem to give mood side effects in many women. They just do not feel well. Natural progesterone may well have less of these mood effects but a large study failed to confirm anecdotal impressions. In that study, progestins caused more breast soreness than natural micronized progesterone but did not seem to show a difference in anxiety, cognition, or affect. More work needs to be done in this area, however, because it is a major reason for hormone replacement difficulty.
If there is a family history of heart disease, which are the best estrogens?
Estrogens have been known to reduce the new occurrence of heart disease since the late 1970's. Since heart disease is the major cause of death in menopausal women, The greatest benefit of estrogen replacement in terms of lives prolonged is the use of estrogens to prevent or delay the onset of heart problems.
Again, we do not know that any estrogen preparation is better than any other in preventing this. We do know that estrogens do have a greater reduction in mortality in woman who are at high risk for coronary artery disease than women who are at low risk. There is currently a debate as to whether women who already have heart disease get any benefit from estrogen replacement. In the short term they do not seem to but some investigators still believe there may be a longer term benefit.
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