Update on Phytoestrogens

By Dr Henri ROZENBAUM
President of French Menopause Study Association
Gynaecologist and Endocrinologist

Phytoestrogens are a group of substances derived from various vegetable species, which are characterised by a certain estrogen activity.

Phytoestrogens are plant-derived molecules of non-steroidal structure, capable of binding to the oestrogen receptor. Depending on their concentration, endogenous sexual steroid levels and the target organ concerned, phytoestrogens may behave agonistically or antagonistically toward oestrogens. On the other hand, a certain number of their properties seem to result from non-genomic mechanisms. There are many phytoestrogens, and their concentration varies considerably from one plant to another and from one preparation to another. Phytoestrogens are considered as food supplements: they are also sometimes called nutrients or nutraceuticals. The products currently most in use come from soya beans. Isoflavones are most often used. Their main active compounds are daidzein and genistein. Several questions arise regarding these OTC products in pharmacies.

Must phytoestrogens be considered as oestrogens?
With the exception of coumestrol, phytoestrogens are characterized by:
   - A greatly reduced affinity for oestrogen receptors than E2 (Oestradiol),
   - A greater affinity for the β receptor than for the α1.
Overall, they have a significantly lower biological effect than oestrogens.

Are phytoestrogens effective against hot flushes?
The reduced frequency of hot flushes in Asia:
   20% in China and 25% in Japan, compared to the West: 75 % in the USA,
has raised the issue of benefits of a soy-rich diet vis-a-vis climacteric symptoms.

But a number of uncertainties persist despite numerous publications on this subject, explained by the importance of variations in individual bioavailability and the great diversity of usable products, in terms of quality as well as dosage. After an extensive review of the literature, Tempfer et al.2 maintain that isoflavones are especially effective in women who have had a recent natural menopause and suffer from moderate disorders. In contrast, the effects are modest in cases of idiopathic premature menopause, menopause induced by cancer treatment, prolonged HRT or if isoflavones

Are phytoestrogens effective against bone loss in postmenopausal women?
Despite several publications having arrived at a favourable conclusion on markers of bone restructuring or on bone density, most authors do not consider phytoestrogens to have a preventive effect against osteoporosis in postmenopausal women3.

Do phytoestrogens entail a carcinogenic risk?
Endometrium
The incidence of endometrial cancer is low in countries where consumption of isoflavones is high4. The vast majority of authors agree in recognizing that as far as usual therapeutic doses are concerned, the use of phytoestrogen does not induce any endometrial risk. A recent publication by Palacios3-5 et al.6 has confirmed the absence of any deleterious effects after three years of treatment: endometrial biopsy study of the thickness of the mucous membrane shows that its dimensions remain identical to those at the beginning of treatment.
Breast, Mammographic Density
Taking phytoestrogens does not alter breast density, a phenomenon confrmed by the recent study by Palacios et al. After 3 years of treatment, the ACR (American College of Radiology) classification, a universally accepted criterion, remained unchanged.
Epidemiological data
The incidence of breast cancer is lower in several Asian countries: Japan, China, Korea and Indonesia, than in the West7. The study of Asians who immigrated to the U.S. is particularly interesting: the incidence of breast cancer is lower among women who immigrated at a later age than among those who immigrated during their youth8. It remains low among those who maintained their eating habits9 while it increases in cases of changing dietary behaviour10. Thus the incidence of breast cancer in Asians catches up with that of Westerners from the first generation of immigrants onwards11.
Epidemiological studies in women taking phytoestrogens
Several observational, case-control or cohort studies were conducted, again with conflicting results: some authors have observed a protective effect induced by a soy-rich consumption, others have not. A meta-analysis12 involving 14 case-control studies and 7 cohort studies results in an RR = 0.75 (0.59 to 0.95), representing a 25% reduction in the risk of breast cancer in women who in the past have consumed soya beans, tofu, miso or isoflavones. Another more recent study that analyzed 174 randomized controlled trials, observed no increased risk of breast cancer among consumers of phytoestrogens5. It is actually a complex problem because of the diversity of phytoestrogens and the many differences between Western and Asian food, which do not concern only food content in phytoestrogens but also in red meat and animal fats, fish, notable Vitamin D sources, etc. On the other hand, the period in which soy is consumed may play a significant role; originally discovered in animals, this fact has recently been observed in human clinical practice, with several studies showing a decrease in further risk of breast cancer among adolescents who received significant soya bean contributions 13-14. In practice however, given the current state of our knowledge, it appears inadvisable to use phytoestrogens in cases of personal history of breast cancer, especially if treatment with aromatase inhibitors is underway.

CONCLUSION

Phytoestrogens, at least some of them, may be useful for treating hot flushes. Though their efficiency with respect to the prevention of bone loss is not proven, we can confirm their safety with respect to the endometrium and breast.

BIBLIOGRAPHY

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