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Case Study Phytoestrogens and Menopause

A 55-year-old postmenopausal patient returns to the clinic 6 months after being prescribed Premarin and Provera for hot flashes, vaginal dry-ness, insomnia, and mood swings. She took hormone replacement therapy (HRT) for 2 months and had significant relief of symptoms. Even so, she noted breast tenderness on this regimen that worried her despite her recent negative mammogram report. When she read in an article that long-term estrogen (>5 years) might increase her risk of breast cancer by up to 30%, she abruptly stopped therapy. Despite the return of her earlier symptoms, she adamantly refused further HRT even when informed again of its effectiveness for osteoporosis. However, she was very interested in pursuing dietary therapy with phytoestrogens, since this is what several women in her church group are doing.

This patient asks how much soy and what type of soy products she must eat to get relief. She questions whether soy phytoestrogens will do "all of the good things and none of the bad," as she has been told. She asks about the safety and effectiveness of other phytoestrogens and about any other "natural" estrogen alternatives to conjugated equine estrogens.

Answer: In spite of the many benefits of HRT, about 80% of prescriptions for it are never filled or are discontinued. Many physicians are frustrated when they discover their patients have stopped therapy without their input, more often than not because of fear of breast cancer. Other commonly cited side effects include weight gain, bloating, and spotting. It appears that the tide of public and possibly even scientific opinion may be turning against estrogen therapy. The Heart and Estrogen/Progesterone Replacement Study trial has demonstrated a possible increase in cardiac events in the first 2 years of therapy, although subsequent cardiac risk appears to decline. Overall there was no benefit in reducing risk of death from chronic heart disease in women at risk. Other trials, including the Nurse's Health Trial, suggest that HRT can be associated with a significant (up to 30%) increase in breast cancer after 5 or more years of use, and more than 10 years of HRT has been associated with increased mortality from ovarian cancer. Finally, the recent National Institute of Health trial demonstrating increased breast cancer and cardiovascular risk associated with HRT has altered professional practice as well as public perception of estrogen's risk.

Phytoestrogen dietary therapy has become increasingly attractive to women in the present climate of care. These substances are not estrogens at all, but they bind to estrogen receptors and may act like selective estrogen receptor modulators. Many plant sources of phytoestrogens were found, including soybeans, other legumes, and flaxseed. Soybeans are among the best sources of the isoflavones genistein and daidzein. Soy may now be consumed in a variety of ways: fresh, frozen, dried, roasted (soy nuts), tofu (soybean curd), tempeh (fermented soybeans and grains), soy milk, soy flour, miso (fermented soy paste), and textured vegetable protein. Some soy products may have lost their isoflavone content in processing: soy cheese, soy oil, and tofu yogurt. Flaxseed contains another type of phyto-estrogen, lignans, as well as omega-3 fatty acids. About 1 tablespoon of flaxseed could be considered equivalent to one serving (50 g) of soy, and flaxseed may be an alternative for those who dislike tofu.

Although there is some controversy about how much soy must be consumed to benefit from its phytoestrogen effect, it is believed that two servings per day will modestly reduce menopausal symptoms and the risk of breast cancer. More than three servings may reduce cholesterol. Although it has yet to be proved that dietary soy will stop osteoporosis, a synthetic isoflavone, ipriflavone, has been used in Japan and Europe to treat osteoporosis. Large doses of soy (6-8 servings per day) are believed by some to help this condition as well.

Phytoestrogens appear to reduce the risk of breast cancer, because their estrogenic effect is actually quite weak (one two-hundredth of estradiol) and yet by occupying estrogen receptors, they protect the breasts from more potent estrogens. In an estrogen-deficient postmenopausal patient, they provide a modest estrogenic effect, while in an estrogen-rich environment they actually protect the breasts from estrogen stimulation. Soy may also block tyrosine kinase, an enzyme necessary for the growth of cancer cells.

Allergies to soy may be a concern for some patients, and there may be a cross-reaction with peanut allergy. Bloating and gas occur, especially in those unaccustomed to soy products.

Some women are rejecting conjugated equine estrogens in favor of preparations containing lower-potency estriol, a weak human estrogen produced in pregnancy and thought to be more protective of the

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