In July 2002 the government announced the early termination of part of a study called the ‘Woman’s Health Initiative’ (WHI). The WHI study was designed to evaluate the effect of hormone replacement in post-menopausal women. The study, planned to last for seven years, was terminated early because of an increased incidence of health problems noted in one portion of the investigation. For many years, estrogen replacement therapy has been a routine recommendation as an effective treatment for disturbing menopause-related symptoms such as hot flashes, insomnia, and vaginal atrophy. Additionally, there is substantial evidence that the bone-weakening effects of osteoporosis are lessened by hormone replacement. This announcement has caused considerable confusion among women either utilizing hormone replacement therapy or considering it. This edition of OHN will hopefully help clarify some of the questions involved in this issue. Additionally, the role of Natural Hormone Replacement and plant-based phytoestrogen usage will be discussed.
The Women’s Health Initiative study evaluated the effects of hormone replacement therapy (HRT) on multiple health conditions, including cardiovascular disease, cancer (breast and colon), blood clots, and osteoporosis. The investigation was conducted in two segements. The portion which was terminated (group 1) involved women who had not had a previous hysterectomy (surgical removal of the uterus). Women in this group received two hormonally active substances; an estrogenic compound (Premarin [trade name] = conjugated equine estrogens = CEE) and a progestin (Provera [trade name] = medroxyprogesterone acetate = MPA). The proprietary name for this combination of Premarin and Provera is Prempro. The other portion of the study (group 2) was designed to evaluate health outcomes in women taking hormone replacement but who have had a hysterectomy. Group 2 women were taking only estrogen (Premarin) and no progestin agent. This portion of the study has not been terminated since no adverse effects have been noted after more than 5 years.
The Group 1 portion of the study was discontinued early because there was noted to be a 26% increase in the incidence of invasive breast cancer (there was no difference in non-invasive breast cancer). The actual numerical increase, in 10,000 women/years was 8 cases. (38 cases of invasive breast cancer among hormone replacement hormone users compared to 30 cases in those taking a placebo). There were somewhat similar increases in the number of cardiovascular events (strokes and heart attacks). The incidence of blood clots was about double in the hormone replacement group (16 vs 34 per 10,000 patient years). If you analyze at the actual number of events occurring in the hormone replacement group vs. placebo, you will see that the increase per 10,000 patient years is actually relatively small (less than 1 case per 1000 patient years) Nevertheless, if you describe these numbers in terms of percentages, it can be somewhat alarming. 38 compared to 30 represents about a 25% increase. To a certain degree, this is a matter of using statistics to make something more dramatic or alarming (or newsworthy). On the positive side of the study, it was noticed that the incidence of osteoporosis and colon cancer were lower in the group taking hormone replacement.
Although the actual increase in risk of invasive breast cancer, cardiovascular disease, and blood clotting issues is relatively small, it is, nevertheless, still present, measurable, and real. Any woman contemplating the use of hormone replacement treatment needs to assess both the risks and benefits in terms of their own personal situation. The final decision whether or not to continue hormone replacement therapy has to rest with each individual, and should be made in consultation with their physician. This has been the official recommendation of the National Institutes of Health (NIH). I personally agree with this position.
If the decision is made that hormone replacement is indicated and desirable, other options are available beyond utilizing synthetic or non-natural hormonal substances. To me it makes a lot more sense, for many reasons, to replace hormones with substances that are bio-identical to the substances made by a woman’s body. Premarin, the most commonly prescribed synthetic estrogen replacement substance, is a formulation consisting of 80% estrone (a naturally occurring human female hormone) and 20% equilin, an estrogenic hormone obtained from the urine of pregnant mares (hence the name Pre- [= pregnant], mar- [=mare], in [=urine]. Humans have enzymes that will break down and eliminate hormones that are produced naturally in the body. Conversly, we do not have enzymes that can eliminate substances that are not normally present in humans. Because of this, non-natural hormones (such as equilin) will stay in the body much longer and exert their effects for a significantly longer period of time. Even when these non-natural substances are broken down, the multitude of downstream metabolites are not compounds familiar to the human body. The effective differences have never been measured, but it is not unreasonable to assume that these unknown effects may not be desirable in all aspects. Many years ago the completely syntheic estrogenic substance DES (diethylstilbesterol) taken by many women to prevent miscarriage. It was eventually removed from the market because of cancer inducing effects in daughters of the women who took this substance. The bottom line in my mind; if hormone replacement is to be considered, it makes a lot more sense to utilize substances that are biologically identical to those naturally made in the human body.
Human estrogen actually consists of three distinct hormones: Estrone, estratiol, and estriol. It is possible to make bio-identical molecules to human estrogens by making minor structural alterations to natural substances extracted from soy plants. These bio-identical hormones can then be formulated into compounds that are equivalent in effectiveness to commercial synthetic products such as Premarin. However, since they are exactly identical in structure to a woman’s naturally occurring hormones, they can be broken down and eliminated in a normal manner. In my mind, it makes inherent sense that these bio-identical substances would be safer than synthetic or non-human estrogenic compounds. There are no long-term studies on bio-identical hormone replacement. Because natural substances cannot be patented, there is no economic incentive to conduct these extensive studies, which can cost many millions of dollars.
There are other advantages to using bio-identical hormone replacement that are beyond the scope of this brief newsletter. A good book on this subject is ‘Natural Hormone Replacement’ by Jonathan Wright MD and John Morgenthaler. (800-543-3873; www.smart-publications.com). If this is a topic of interest to you it is definitly worth having in your library. Another book that discusses primarily the use of Progesterone, another female hormone, is ‘What your doctor may not tell you about menopause’ by John R. Lee MD. This is also an excellent book and a source of information that I would strongly recommend.
Many women who are experiencing problems with peri-menopausal or menopausal symptoms can obtain significant relief by utilizing plant (principally soy) based derivatives called ‘phytoestrogens’. These substances, although they are significantly less potent, are structurally similar to human estrogens. Because of this, they can bind at hormone receptor sites and function as weak estrogens, reducing or eliminating many of the unpleasant symptoms associated with menopause. Numerous studies have shown that people with highest levels of phytoestrogens have lowest risk of breast cancer. It is thought that the lack of menopausal symptoms in Japan is related to a high consumption of soy and soy-based products. The Japanese language has no words that mean ‘hot flash’ (this is an arguable issue - if you have any friends that speak fluent Japanese, ask them). Flax contains substances called ‘lignans’ that can reduce menopausal symptoms and have been shown to be associated with a reduction in invasive breast cancer. Black Cohosh is an herb that has been studied extensively and, in some women, can be quite effective in reducing symptoms of menopause. It is certainly worth a try.
Best regards,
Subsequent to the writing to this OHN in 2002 a newer program for utilization of Female Hormone Replacement Therapy has been described. This is commonly referred to as the ‘Wiley Protocol’ and has become quite popular in the Santa Barbara area. A subsequent edition of OHN has been written which deals specifically with this approach. To read this, either return to the OHN directory page, or click on the following link: - 'Wiley Protocol'