The Search for Alternative Therapies for Menopausal Women: Estrogenic Effects of Herbs

Karen M. Prestwood

Center on Aging, University of Connecticut Health Center Farmington, Connecticut 06030-5215

Address all correspondence and requests for reprints to: Karen M. Prestwood, M.D., Associate Professor Medicine, Center on Aging, University of Connecticut Health Center, Farmington, Connecticut 06030-5215. E-mail: prestwood{at}nso1.uchc.edu.

Approximately 1 yr ago, millions of women awoke to newspaper headlines questioning the safety of hormone replacement therapy (HRT), a treatment that many women were taking to relieve menopausal symptoms and to prevent heart disease and osteoporosis. The Women’s Health Initiative (WHI) Study reported increased risk of cardiovascular disease, breast cancer, stroke, and thromboembolic disease with conjugated equine estrogen plus medroxyprogesterone acetate (HRT) compared with placebo, and that component of the study was halted (1). Meanwhile, the arm of the study examining the benefits and risks of estrogen alone vs. placebo continued and is still ongoing. Since the original report alerting us to the risks of HRT, the WHI study group has also demonstrated that quality of life (2) and cognition (3) are no better in the HRT group than the placebo group. The benefits of HRT from WHI were reduced incidence of hip fracture and colon cancer as well as relief of menopausal symptoms (1). Many previous studies demonstrated the beneficial effect of estrogen replacement therapy/HRT on bone density, but this was the first large randomized trial to confirm that HRT reduced hip fracture. Recent studies suggested that lower doses of estrogen and progesterone than used in WHI were effective in preventing bone loss and reducing hot flashes in postmenopausal women, even those in the early menopause (4, 5, 6). In older women, ultra low-dose estrogen (one fourth of the usual dose) reduced bone resorption to the same degree as usual dose estrogen in a short-term study (7). The ultra low-dose (0.25 mg/d) estrogen also increased bone mineral density and decreased bone turnover in older women over 3 yr with few adverse events (8). Overall, these data suggest that lowering the dose of estrogen and progesterone may reduce menopausal symptoms and enhance bone health without increasing adverse effects as seen in WHI.

Given the positive effects of lower dose estrogen, it is plausible and logical to look for substances that have less affinity for the estrogen receptor than estradiol in the hope of identifying herbs or nutritional supplements that reduce menopausal symptoms and, perhaps, benefit bone without the adverse effects associated with HRT. The study published by Oerter Klein et al. (9) in this issue of JCEM describes a technique to examine the bioactivity of estrogen in various herbs known to have some effect on menopausal symptoms. The assay was developed originally to assess low levels of estradiol in children and postmenopausal women and was modified for this study. The assay provides information related to estradiol equivalents per microgram of herb and so allows the reader to directly compare estrogenic activity of different herbs. Some interesting findings came from the study: fo-ti, a Chinese herb, has similar estrogenic activity as soy (1/300 the potency of estradiol); and the aglycone form of soy had an even higher estrogen activity than soy. The estrogenic activity of soy, red clover, and licorice has been reported previously and is confirmed in this study. Black cohosh, chaste berry, and dong quai, herbs that have been used for menopausal symptoms, did not have any estrogenic activity by this assay or in previous studies (10, 11, 12, 13). Clinical studies on the effectiveness of black cohosh and soy to reduce menopausal symptoms have been mostly positive, whereas studies of red clover and don quai have been negative (14, 15, 16). Soy and black cohosh can be recommended to postmenopausal women to ameliorate menopausal symptoms (14, 17), however, the long-term risks and benefits of these agents in postmenopausal women are not yet known. Furthermore, data regarding the effect of soy on breast health are conflicting, with most studies demonstrating an antiestrogenic effect and some studies an estrogenic effect (18, 19). Longer term studies are currently under way to examine the benefits of soy and black cohosh in postmenopausal women.

Fo-ti, also known as He Shou Wu, is a Chinese herbal medicine used as a secondary adaptogen. It is used in combination with other herbs to treat symptoms of chronic disease such as general weakness, poor appetite, fatigue, and weight loss; it is also used to darken hair color. Chinese herbs are typically administered in combination to maximize benefit and to minimize adverse effects; the herbs balance the human system and each other. To date, there have not been any reports of fo-ti being used for the alleviation of menopausal symptoms or prevention of osteoporosis. In traditional Chinese medicine (TCM), the kidneys are believed to be the foundation of life. As such, the right kidney (energetically Yang) provides the spark to the organs to do their jobs effectively and the Yin kidney provides fluids necessary to cool the body and provide lubrication to joints as well as promote vaginal fluids, intestinal fluids, and stomach fluids. Menopausal symptoms, from the TCM point of view, are often related to a kidney Yin deficiency. One of the TCM uses of fo-ti is to tonify (or strengthen) the kidney, thus building Yin (20). From a TCM standpoint, then, this herb may be of benefit to postmenopausal women. Thus, potential mechanisms of action related to the use of fo-ti in postmenopausal women exist in both TCM and Western medical systems.

With the new information reported in this issue of JCEM, relating to the estrogenic activity of fo-ti, clinical studies will likely be initiated to examine its role in postmenopausal women. However, because fo-ti has been traditionally used in combination with other herbs, it is unclear whether its use as a single agent will be beneficial or whether any potential side effects will become more prominent. In the case of fo-ti, those side effects are diarrhea and digestive problems. As we begin to screen and test herbs for potential estrogenic effects, it seems prudent to look at the traditional uses of herbs in China and other cultures and to take advantage of thousands of years of experience with herbs. By integrating ancient knowledge with modern technology, we may find several options to reduce the effects of estrogen deficiency on postmenopausal women. The study by Oerter Klein et al. (9) is one method of assessing estrogenic activity of herbs and has provided new information about fo-ti. Further research is required to fully elucidate the benefits and risks of fo-ti used as a single agent or in combination with other herbs in postmenopausal women.

Footnotes

Abbreviations: HRT, Hormone replacement therapy; TCM, traditional Chinese medicine; WHI, Women’s Health Initiative.

Received July 23, 2003.

Accepted July 23, 2003.

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