Title: The risks and benefits of the isoflavones in women’s health


Key words: isoflavones, plant phenols, oestrogen, oestrogenic, oestrogen-like, HRT, menopause, menopausal, pre-menopausal peri-menopausal, soya, oestrogen receptors, menstrual cycle, LH, FSH, osteoporosis, CVD, cardiovascular disease, calcium, lipid peroxidation, follicular phase, flushing, cholesterol, lipid, atherogenic, soya protein, antioestrogenic, antioxidant, antimitotic, antiprotease, antiangiogenesis, diethyloestrogen,  


Date: Sept 2006




Nutrimed Module:


Type: Article


Author: Morgan, G


The risks and benefits of the isoflavones in women’s health

Isoflavones, a class of plant phenols, have been extensively investigated in recent years due to their oestrogen-like properties. Like HRT they have been linked with favourable health benefits in menopausal women. Their use as HRT replacements and their possible side effects in this age group and in children will be reviewed here.

Isoflavones possess weak oestrogenic properties, but, in the quantities ingested in the Far Eastern diet in the form of soya-derived products, they promote significant biochemical and physiological effects (White 2000). Their effects are mediated through oestrogen receptors for which they compete with endogenous oestrogen. They selectively bind to oestrogen beta-receptors found in brain, bone, bladder and the vascular endothelium (Kuiper 1997). This may partly explain their beneficial oestrogenic effects though it is known that isoflavones can also exert a modulating influence on endogenous oestrogen activity (Xu 2000).

Direct oestrogenic effects on the menstrual cycle occur with isoflavone use. Inhibition of LH and FSH secretion, prolongation of the follicular phase and menstrual cycle and some reduction in menopausal flushing has been demonstrated (Cassidy 1994, Brzezinski 1997). Indirect effects are reflected in the reduced incidence of osteoporosis and cardiovascular disease amongst soya consumers (Potter 1998, Alekel 2000, Somekawa 2001, Setchell 1995, Anderson 1995).


Laboratory experiments have shown isoflavone effects on calcium, lipid and protein metabolism, oxidative pathways, lipid peroxidation, the migration of vascular smooth muscle cells and on cell differentiation. It seems likely that these effects explain the ability of isoflavones to lower blood cholesterol, normalise lipid profiles and prevent the atherogenic process (Crouse 1999, Washburn 1999,Tikkanen 1998). Some of these effects may be directly metabolic and not oestrogen-mediated. In the case of osteoporosis, some of the efficacy of soya consumption has been shown to be due to inhibition of urinary calcium excretion by soya protein (Breslau 1988). This highlights the point that isoflavones, soya and confounding factors should be all considered in any analysis of these issues.


The oestrogenic effects of isoflavones has raised concerns that these compounds might promote the development of oestrogen-dependant tumours such as breast and endometrial cancer. Petrakis, in a frequently quoted study (Petrakis 1996), reported increased epithelial proliferation and glandular secretion in breast tissue exposed to isoflavones but this study has been criticised for its design and conclusions. Another study (Panno 1996) showed reduced mitotic activity in breast cells exposed to physiological levels of endogenous oestrogens and isoflavones. In animal models prepubertal exposure to isoflavones, though associated with ductal hyperplasia, was associated with a reduced incidence of adult cancer of the breast (Murrill 1996, Fritz 1998).


In humans an epidemiological survey of Japanese Americans indicated that those exposed to soya from birth showed a reduced incidence of cancer extending into the menopause (Wu 1998). There are no studies indicating that soya consumption initiated in the premenopausal period is associated with an increased cancer risk. Much in vivo research attests to an antioestrogenic and anticancer effect of the isoflavones associated with antioxidant, antimitotic, antiprotease and antiangiogenesis effects (Wei 1995, Lamartiniere 1995, Akiyama 1987, Supko 1995) which supports their safety.


Concerns have also been voiced about the advisability of soya milk consumption during infancy and childhood. There was a fear that oestrogenic effects might, as exhibited by the synthetic oestrogen diethyloestrogen, be associated with developmental disorders of the genital tract or later menstrual disorders and carcinogenesis. Consumption in infancy leads to much higher plasma isoflavone levels than in adults (Setchell 1997) but, in spite of this and after many years of soya milk use in clinical practice, there are no validated surveys documenting any ill effects.


Finally, studies indicate a quantitative benefit to soya consumption. Animal and epidemiological studies show not only benefits from early consumption but also from higher levels of consumption. Intakes of above 50mgs per day have been shown to produce significant improvements in bone and cardiovascular health in women, particularly in the postmenopausal group (Potter 1998, Somerkawa 2001, Crouse 1999). These are levels which are unlikely to be reached by a Western diet and raise the question of the future therapeutic use of functional foods or supplements in the West.




1. White LR. (2000) Brain aging and midlife tofu consumption. J Am Coll Nutr. 19: 242-255

2. Kuiper GG, et al. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138: 863-870

3. Xu X. (2000) Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Pre.9: 781-786

4. Cassidy A, Bingham S, Setchell KDR. (1994) Biological effects of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 60: 333-340

5. Brzezinski B. (1997) Short term effect of phytoestrogen-rich diet on postmenopausal women. Menopause 4: 189-195

6. Potter SM. (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68: 1375S-1379S

7. Alekel A. (2000) Isoflavone-rich soy protein isolate attenuates bone loss  in the lumbar spine of perimenopausal women. Am J Clin Nutr  72: 844-852

8. Somekawa S (2001) Soy intake related to menopausal symptoms, serum  lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 97: 109-115

9. Setchell KDR. (1995) Non-steroidal estrogens of dietary origin: possible role in health and disease, metabolism and physiological effects. Proc Nutr Soc NZ 20: 1-21

10. Anderson JWE. (1995) Meta-analysis of the effects of soya protein intake on serum lipids. N Eng J Med 333: 313-315

11. Crouse JR (1999) Randomised trial comparing the effect of casein with that of soya protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med 159: 2070-2076

12. Washburn S. (1999) Effect of soya protein supplementation on serum lipoproteins, blood pressure and menopausal symptoms in peri-menopausal women. Menopause 6: 7-13

13. Tikkanen MJ, et al. (1998) Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci  USA 95: 3106-10

14. Breslau NA, et al. (1988) Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrin

 Metab 66: 140-146

15. Petrakis NL. (1996) Stimulatory influence of soy protein isolate on breast secretion in pre-menopausal breast. Cancer Epidemiol  Biomarkers Prev 5: 785-794

16. Panno ML, Salerno M, Pezzi V, et al. (1996) Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells. J Cancer Res Clin Oncol  122: 745-749

17. Murrill WB, et al. (1996) Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats. Carcinogenesis 7: 1451-57

18. Fritz WA. (1998) Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 19: 2151-2158

19. Wu AH. (1998) Soy intake and the risk of breast cancer in Asian and Asian-Americans. Cancer Epidemiol Biomarkers Pre 68: 1437S-43S

20. Wei H, Bowen R, Cai Q, Barnes S, Wang Y. (1995) Antioxidant and  antipromotional effects of soybean isoflavone genistein. Proc Soc Exp Biol Med 208: 124-130

21. Lamartiniere CA, et al. (1995) Genistein suppresses mammary cancer in rats. Carcinogenesis 16: 2833-2840

22. Akiyama T, Ishida J, Nakagawa S, et al. (1987) Genistein: a specific inhibitor of tyrosine-specific protein kinase. J Biol Chem 262:5592-5

23. Supko G. (1995) Plasma pharmacokinetics of genistein in mice. Int J Oncol 7: 847-854

24. Setchell KDR, Zimmer-Nechemias, Cai J, Haub JE. (1997) Exposure of infants to phytoestrogens from soy-based infant formulas.  Lancet 350: 23-27