Added online March 2010
Bioidentical Hormones: One Clinician's Perspective
It has been estimated that by 2015, nearly 50% of the women in the US will be menopausal and that the menopausal population in the US will have doubled between 1990 and 2020. This dramatic increase in the number of menopausal women is influencing politics, economics, relationships, product development, media, and medicine. It is changing not only the way health care providers work with women, but the health-care system itself. At no other time in history have we had so many individuals dealing with the same set of health care issues. Now more than ever, clinicians and their patients have options for the management of menopause: diet, exercise, stress management, nutrition, botanicals, bioidentical hormones, synthetic and other conventional hormones, and additional pharmaceuticals.
Many women have long struggled with making decisions about contraception and hormone therapy. Since July 2002 and the first published paper from the Women's Health Initiative (WHI), many more women are now finding making decisions about menopause and hormone therapy confusing, complicated, and difficult. Women typically look to their health-care providers for definitive answers to their questions: What are the benefits of hormone therapy (HT)? What are the risks of HT? In the face of complex, contradictory, and incomplete research on HT for menopausal women, practitioners are now faced with an even greater challenge of evaluating the benefits and risks for each patient. After over 50 years of published research on menopausal HT, thousands of studies, and millions of women on and off HT, some very big questions are still without clear answers. Does long-term HT increase the risk of breast cancer? Does long-term HT increase or decrease the risk of cardiovascular disease? Does long-term HT increase or decrease the risk of Alzheimer's dementia? In all of these areas, you can point to significant published data that says HT does and significant published data that says HT does not. What is a woman to do?
Unfortunately, many menopausal women have a limited understanding of the long-term health risks associated with this change in hormone status, and very few women believe that they are well informed about the benefits and risks of HT. Each woman wants to know whether hormone replacement therapy is right for her. She wants to know how she may benefit, how long she will have to take it to receive those benefits, and what the short-term side effects are as well as the potential long-term negative effects. She also wants to know which dose is safer, which brings more cause for concern, and from which kind of hormones and in what delivery method she might benefit with less or no risk.
Scientific evidence regarding the use of postmenopausal hormone therapy comes in many forms: observational studies, large-scale randomized trials, small clinical trials, biological plausibility, in vitro studies, and animal studies. Other factors involved in the hormone conundrum include theoretical questions, areas of scientific uncertainty, popular consumer opinions and fears, and insufficient research in the area of bioidentical hormones. Landmark studies seemed to offer clarity in a few areas. For example, the HERS (Heart and Estrogen/progestin Replacement Study) I trial did show that oral micronized natural progesterone was adequate to protect the endometrium, and the trial results showed that this progesterone had a more favorable effect on lipids than did the progestin. HERS I and HERS II were the first randomized controlled clinical trials that demonstrated that HT was not protecting women from heart disease, as was previously thought. Despite the HERS trials, and the WHI data, however, there is still a lot left to clarify. One of the greatest areas of debate is this: does HT increase or decrease the risk of heart disease? While the HERS trials and the WHI seemed to clearly state there was an increased risk when using Premarin and Provera, other research demonstrates that HT reduces the risk of heart disease if it is started in perimenopause or early menopause. In essence, if women start HT early in menopause, it may be cardioprotective. Women and their health-care practitioners are faced with trying to make significant decisions in the face of what we do know, what we don't know, and what we still find uncertain.
It is important to understand that most of the research in the US on hormone regimens is on conjugated equine estrogens (CEE, also known as Premarin) and medroxyprogesterone acetate (MPA, also known as Provera). However, that is not exclusively the case, and certainly some of the cardiovascular research has equally implicated 17 beta estradiol (bioidentical estradiol). Nonetheless, in the most damaging data to date, the HERS I and II trials and the WHI, the hormones used were Premarin and Provera. So, what we definitely know to be negative effects are associated with those regimens, and what we do not know is if the data translates to other regimens. It would be naïve to dismiss the data and the possibility that the results would be the same, but when hormones are determined to be appropriate or even necessary, it would seem logical to use the hormones that we at least know are not the ones causing adverse effects. In addition, let me share some thoughts and information about why bioidentical hormones are preferable at this point in history.
Bioidentical estrogens and bioidentical progesterone, as well as bioidentical testosterone and DHEA, such as those made by compounding-l pharmacies (in addition to the natural progesterone creams sold over the counter) are distinct in several critical ways from conjugated equine estrogens, conjugated plant estrogens, synthetic estrogens, and synthetic progestins. Bioidentical hormones are made from either beta sitosterol extracted from the soybean or from diosgenin extracted from Mexican wild yam root. Those compounds are then made into the desired hormone, and the end result is that they are biochemically identical to the hormone the body produces. By definition, a bioidentical or natural hormone is plant-derived and bioidentical to endogenous hormones. The bioidentical compounded estrogens currently made are estriol, estrone, and estradiol. Estriol is unique in that it is approximately one-fourth the potency of estradiol and estrone.
Bioidentical estrogens acquired from a compounding pharmacy are available in any dose that can be clinically requested. Generally, these estrogens are used in lower doses, due to the combined effect of the weaker estriol along with the estradiol and/or estrone. These bioidentical estrogens are thought to be metabolized significantly differently by the body. They have a shorter half-life. They can be used in customized dosing regimens and in potencies that fit each woman and clinical situation, and they can be adjusted to be stronger or weaker in small units when a woman is tapered off or onto hormones.
Conjugated equine estrogens, or Premarin, is quite different. In the 1970s, it was believed that Premarin only consisted of ten estrogens: 17 beta estradiol, 17 beta dihydroequilin, 17 beta dihydroequilenin, 17 alpha dihydroequilin, 17 alpha estradiol, estrone, equilin, 17 alpha dihydroequilenin, delta 8-9 dehydroestrone sulfate, and equilenin. Since then, advancements in technology have revealed that the original ten estrogens make up less than 40% of the hormonal content of Premarin. With modern analytical techniques, today over 200 individual components have been identified, including androgens and progestins. The composition of Premarin is complex, and different estrogens produce various effects in different tissues. Herein may lie an explanation for problems with conjugated equine estrogens versus natural bioidentical estradiol, estrone, and estriol. Dr. Joel Hargrove has shed some light on these distinctions for years. I credit his analysis and paraphrase the following with some of my own thoughts.
The steroid hormones, including the sex steroids produced by the ovary, represent a subclass of lipids that share a four-ring steroid structure. The native compound from which all the sex steroids are derived is cholestane, the parent of cholesterol. When nutritional states of the individual and cell are normal, the principal precursor of steroid production is cholesterol in the plasma. The cholesterol enters the cells through a lipoprotein receptor system. The activity of the enzymes within the cells of that tissue are the determining factor for that tissue to produce a particular class of steroids. Steroids, either endogenous or exogenous, enter the cells via passive diffusion. The tissues that respond to steroids have specific intracellular receptors with a high affinity for their particular steroid. The primary action of the steroid is the binding of a steroid hormone to a receptor and the interactions of this receptor-hormone complex with the components of the cell. When the steroid binds, the steroid-receptor complex becomes activated and binds with specific regions within the steroid-responsive region of the genes. Most of the effects of steroids on responsive cells are mediated through the activation of specific genes. The hypothesis is that a non bioidentical hormone may act like a constant environmental toxin to the genetic material within the cell, because even though it can bind to the receptor hormone complex, it is a foreign substance.
CEE is a part of the complex of over 200, mostly foreign, substances within a human and, therefore, are activating those genes within the cell. This, I contend, is a profound distinction between a nonbioidentical hormone and a bioidentical hormone. Besides the effect on the genes themselves, bioidentical hormones and nonbioidentical hormones may very well leave a different metabolic footprint on the rest of the body with different metabolic consequences. They may be directly cytotoxic to estrogen-sensitive tissues, alter binding of other hormones to those receptors, or alter the liver's metabolism of carcinogens. It is this distinction and potential difference in metabolic consequences, as well as the shorter half-life of natural hormones, that motivates me to use almost exclusively bioidentical estrogens, progesterone, and testosterone. In addition, bioidentical hormones from the compounding pharmacies come in any dose and combination that I might need, and they are available without the preservatives, adhesives, dyes, binders, and fillers found in the limited dosing options available from pharmaceutical companies.
The distinctions between synthetic progestins and progesterone is more clear than between different estrogens. Natural progesterone has been studied and shown to have fewer adverse effects on the cardiovascular system than do synthetic progestins such as MPA. Specifically, natural progesterone lowers HDL significantly less than MPA, is less atherogenic, and does not cause coronary artery spasm, whereas MPA does. In perhaps the most compelling study to date, done in France, transdermal bioidentical estradiol plus oral micronized progesterone was not associated with an increased risk of breast cancer, whereas transdermal estradiol with progestins did increase the risk.
Bioidentical estradiol may not be without concerns for the cardiovascular system and breast. However, again, bioidentical estradiol is typically used in lower doses because we combine it with the weaker estrogen, estriol. Although in its research infancy, estriol has been shown to show some ability to act as an antiestrogen in the breast and to show no significant impact on the cardiovascular system.
Further considerations of a bioidentical hormone approach and a more holistic approach to menopause would be to use the hormones in combination with other strategies that are known to reduce the risk of breast cancer and heart disease. For example, soy, flaxseeds, cabbage-family foods, and supplements such as indole-3 carbinole and DIM can alter the metabolism of estrogens and break them down to their less carcinogenic end-products. Breast-cancer and heart-disease prevention diets and lifestyle issues can also be emphasized along with a consideration of nutritional and botanical supplements such as vitamins E and C, carotenes, soy, coenzyme Q10, green tea, garlic, and others.
Using a nature-based philosophy of medicine, common sense, logic, over 21 years of clinical experience, and a small amount of research, I have concluded that bioidentical hormones are the best way to meet my objectives when hormone therapy is needed: help my patients feel better, give the lowest dose possible to meet the desired clinical effects, use medicines in the safest form known, and give women options and the education to help them choose for themselves.
It should also be stated that practitioners who are prescribing bioidentical hormones should not be naïve or blindly assume that bioidentical hormones are without risks while making the accusation that all other hormones are dangerous. The scientific research is just not available to support this kind of perspective. Practitioners must be encouraged to reevaluate their patient's hormone regimen on a regular basis (yearly, at minimum) to establish the lowest dose to achieve the benefits and minimize any risks. Regular, at least annual, consideration also should be given to the duration of use on an individual basis.
It is also important to remember that many women will not need, or want, hormone therapy, even bioidentical HT. Herbal and nutritional supplements may be all that is necessary or wanted. Studies on black cohosh, red clover, soy, bioflavonoids, kava, and proprietary combination formulas have all shown proven scientific efficacy in menopausal symptoms, although, admittedly, these results are not consistent or sufficient. Many women will only require these nonhormonal supplements for their symptom relief and never need any kind of hormone therapy. Other women may be able to lower their dose of HT while using them in combination with the herbal and nutritional supplements.
I offer a few other thoughts to keep in mind:
Great spirits have always encountered violent opposition from mediocre minds.
– Albert Einstein
Science is the search for truth – it is not a game in which one tries to beat his opponent, to do harm to others.
– Linus Pauling
Do no harm.
Dr. Tori Hudson graduated from the National College of Naturopathic Medicine (NCNM) in 1984 and has served the college in many capacities over the last 25 years. She is currently a clinical professor at NCNM and Bastyr University, has been in practice for 25 years, is the medical director of the clinic A Woman's Time in Portland, Oregon, and director of research and development for Vitanica, a supplement company for women. She is also a nationally recognized author, speaker, educator, researcher, and clinician.
Tori Hudson, ND
2067 NW Lovejoy St.
Portland, OR 97209 USA