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Departments of Public Health Sciences and * Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC
2To whom correspondence should be addressed.
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INTRODUCTION |
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 TOP INTRODUCTION Summary and Suggested...REFERENCES |
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Observational studies and clinical trials of HRT in postmenopausal
women have generally shown a beneficial effect on cardiovascular
disease risk, a significant improvement in bone density, a reduction in
the number and severity of vasomotor symptoms (e.g., hot flashes or
night sweats) and a potential beneficial effect on cognitive decline
and dementia in older adults (Barrett-Connor and Grady 1998
, Yaffe et al. 1998
). In terms of adverse
effects, long-term HRT use is associated with an increased risk of
breast cancer (Colditz et al. 1995
); an increased risk
of endometrial cancer is observed in women with a uterus, which
necessitates the addition of progestins to the estrogen regimen
(Barrett-Connor and Grady 1998
), and there exists an
increased short-term risk of thromboembolic events in women with
existing cardiovascular disease (Hulley et al. 1998
).
Data from population-based studies suggest that only 12–21% of
U.S. postmenopausal women currently use HRT, suggesting that there is a
large group of women who either will not or cannot use HRT
(Manolio et al. 1993
, Nabulsi et al. 1993
). Because of this mixed picture for HRT, efforts are
underway to identify agents that may have a better risk/benefit
profile.
Countries consuming large amounts of soy have an improved chronic
disease burden compared with countries consuming very little soy
(Boring et al. 1994
, Thom et al. 1992
)
Specifically, Japanese women have fourfold lower rates of
cardiovascular disease mortality and breast cancer mortality, lower
endometrial cancer rates and reported vasomotor symptoms that are
nearly 10-fold lower than in U.S. or other Western women. Importantly,
studies in migrants suggest that Japanese migrants to the U.S. mainland
approach the rates of the cardiovascular and reproductive cancer of
U.S. women (Robertson et al. 1977
).
An intriguing property of soy isoflavones is their modest agonist
effect on the ß estrogen receptor (approximately one third as potent
as estradiol) and weak effect on the 
estrogen receptor (0.001 as
potent as estradiol) (Kuiper et al. 1998
). Thus, soy
isoflavones can be viewed as a type of selective estrogen receptor
modulator. Randomized trials have been conducted to assess the effects
of soy isoflavones on chronic disease. Specific findings include
beneficial effects on lipids and lipoproteins, with a decline in total
cholesterol (9%), LDL cholesterol (13%), and triglycerides (11%) and
an increase in HDL cholesterol (2.4%) (Anderson et al. 1995
). Animal studies have shown a beneficial effect on
reducing atherosclerotic burden in coronary arteries of nonhuman
primates (Anthony et al. 1997
). Soy isoflavones appear
to have only a modest beneficial effect on bone density in human
studies, whereas animal models (often using higher doses) suggest a
larger effect on bone density (Arjmandi et al. 1998
).
Effects on vasomotor symptoms have been mixed. A few studies using
higher doses of isoflavone (50–80 mg/d), enrolling women with more
vasomotor symptoms at baseline (4–7 symptoms/d) and with larger sample
sizes, have shown mildly beneficial effects on self-reported
frequency and severity of vasomotor symptoms (Albertazzi et al. 1998
, Washburn et al. 1999
). However, it is
important to note that at the doses tested, the effects on vasomotor
symptoms are much smaller than those observed with traditional HRT. The
data for soy isoflavones on breast cancer risk suggest either a neutral
or a mildly beneficial effect on risk (Messina 1999
).
Evidence in both human and animal models suggests that soy isoflavones
do not increase endometrial proliferation (Cline and Hughes 1998
). For cognitive decline and soy isoflavone intake,
scientific data are mixed. Uncontrolled observational studies suggest
that increased tofu in the diet was associated with declines in
cognition in a study of Japanese American men in Hawaii (White et al. 1996
). Animal data suggest that there may be a
beneficial effect of soy isoflavones on neuroanatomy and simple memory
tasks (Pan et al. 1999
). This issue remains unclear,
because no human trial data are available documenting the short- or
long-term effects. Current evidence suggests that isolated soy
protein and isoflavones are well tolerated with no evidence of
bleeding, breast tenderness or gastrointestinal symptoms in
postmenopausal women.
There are a number of subgroups for whom very few data are available on the potential risk or benefit from soy-containing isoflavones. No data are available documenting whether isoflavones will have a beneficial or detrimental effect in women with a history of breast cancer. In women with osteoporosis and osteoporotic fractures, the current evidence suggests that in light of the beneficial effect of HRT and the relatively mild effects of soy, these women should not be encouraged to consider soy isoflavones as a viable alternative for treating their disease.
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Summary and Suggested Recommendations |
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|
TOPINTRODUCTIONSummary and Suggested...REFERENCES |
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. Beneficial effects on cardiovascular disease were observed with soy
isoflavones and traditional HRT; menopausal symptom and osteoporosis
relief are significantly greater with HRT, and no adverse effect on
breast or endometrial cancer is present with soy isoflavones. Few data
exist on the effect on cognition with soy isoflavones, whereas some
studies have observed beneficial effects with HRT. Finally, there are
more adverse symptoms observed with traditional HRT than with soy
isoflavones (e.g., bleeding, breast tenderness or headaches). Taken in
aggregate, soy isoflavones should not be viewed as a viable alternative
to traditional HRT on the basis of current data. It is important to
note that a large number of excellent randomized clinical trials
assessing both dietary soy supplements and isoflavone pills are
underway at present. When these trials are completed, we may be better
able to reevaluate the issue of soy isoflavones as an alternative HRT.
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FOOTNOTES |
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REFERENCES |
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|
TOPINTRODUCTIONSummary and Suggested...REFERENCES |
|---|
1. Albertazzi P., Pansini F., Bonaccorsi G., Zanotti L., Forini E., De Aloysia D. The effect of dietary soy supplementation on hot flushes. Obstet. Gynecol. 1998;91:6-11[Medline]
2.
Anderson J. W., Johnstone B. M., Cook-Newell M. E. Meta-analysis of the effects of soy protein intake on serum lipids. N. Engl. J. Med. 1995;333:276-282
3.
Anthony M. S., Clarkson T. B., Bullock B.C. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis in male Cynomolgus monkeys. Thromb. Vasc. Biol. 1997;17:2524-2531
4. Arjmandi B. H., Birnbaum R., Goyal N. V., Getlinger M. J., Juma S., Alekel L., Hasler C. M., Drum M. L., Hollis B. W., Kukreja S. C. Bone sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am. J. Clin. Nutr. 1998;68:1364S-1368S[Abstract]
5. Barrett-Connor E., Grady D. Hormone replacement therapy, heart disease, and other considerations. Annu. Rev. Public Health 1998;19:55-72[Medline]
6. Boring C. C., Squires T. S., Tong T., Montgomery S. Cancer statistics 1994. CA - Cancer J. Clin. 1994;44:7-26[Medline]
7. Cline J. M., Hughes C. L., Jr Phytochemicals for the prevention of breast and endometrial cancer. Cancer Treat. Res. 1998;94:107-134[Medline]
8.
Colditz G. A., Hankinson S. E., Hunter D. J., Willett W. C., Manson J. E., Stampfer M. J., Hennekens C., Rosner B., Speizer F. E. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N. Engl. J. Med. 1995;332:1589-1593
9.
Hulley S., Grady D., Bush T., Furberg C., Herrington D., Riggs B., Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. J. Am. Med. Assoc. 1998;280:605-613
10.
Kuiper G. G., Lemmen J. G., Carlsson B., Corton J. C., Safe S. H., Van der Saag P. T., Van der Burg B., Gustafsson J. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998;139:4252-4263
11.
Manolio T. A., Furberg C. D., Shemanski L., Psaty B. M., O’Leary D. H., Tracy R. P., Bush T. L. Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group. Circulation 1993;88:2163-2171
12.
Messina M. J. Legumes and soybeans: overview of their nutritional profiles and health effects. Am. J. Clin. Nutr. 1999;70:439S-4350S
13.
Nabulsi A. A., Folsom A. R., White A., Patsch W., Heiss G., Wu K. K., Szklo M. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators. N. Engl. J. Med. 1993;328:1069-1075
14. Pan Y., Anthony M., Clarkson T. B. Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats. Proc. Soc. Exp. Biol. Med. 1999;221:118-125[Medline]
15. Robertson T. L., Kato H., Rhoads G. G., Kagan A., Marmot M., Syme S. L., Gordon T., Worth R. M., Belsky J. L., Dock D. S., Miyanishi M., Kawamoto S. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease. Am. J. Cardiol. 1977;39:239-243[Medline]
16. Thom, T. J., Epstein, F. H., Feldmen, J. J., Leaverton, P. E. & Wolz, M. (1992) Total morbidity and mortality from heart disease, cancer and stroke from 1950 to 1987 in 27 countries. National Institutes of Health Publication No. 92–3088, Bethesda, MD.
17. Washburn S., Burke G. L., Morgan T., Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999;6:7-13[Medline]
18. White L., Petrovitch H., Ross G. W., Masaki K. Association of mid-life consumption of tofu with late life cognitive impairment and dementia: the Honolulu-Asia Aging Study. Neurobiol. Aging 1996;17:5121(abs.)
19. Yaffe K., Grady D., Pressman A., Cummings S. Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women. J. Am. Geriatr. Soc. 1998;46:816-821[Medline]
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