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Dietary phyto-oestrogens
and the menopause in Japan

The Lancet, Vol. 339: page 1233, May 16, 1992

Nancho Advisory: Phyto-estrogens are plant-derived estrogenic molecules which can, like normal female hormones, destroy testosterone and the chemical basis of male maturation and masculinity. The strongest dietary plant estrogens come from soybeans (indeed the powerful daidzein is named directly after daizu, the Japanese soybean), but they also occur in buckwheat, chickpeas, hops, and other foods traditionally fed to the "underclasses" in various cultures. Although the subject of this study was the inexplicable gentleness of the Japanese menopause, the implications of such a drug-grade estrogenic diet for young boys should be apparent. Add this factor to the intense anti-androgenic examination stress that Japanese boys endure during puberty and it becomes a bit clearer why Japan's salarimen come so close to the corporate Ming eunuch ideal. (When I asked Dr. Honjo, the head of the Japanese research team, about the potential effects on male children, she said "our results suggest a potentially serious problem that deserves immediate attention, but who would ever fund the research?") All added emphases in the text below are ours.

Lock, in an article on the menopause1, has discussed differences between Japanese women and women in western societies. Japanese women have a much lower frequency of hot flushes than women in Canada. Lock concluded that "cultural indifference to the hot flush in Japan" was unlikely to account fully for these findings.

Recently our Helsinki group studied, in collaboration with Japanese scientists, the diet and phyto-oestrogen excretion in Japanese women and men, and in a few children.2 The women's mean age was 50.4 (SD 18.0) years and they were all from a small village south of Kyoto and consumed a traditional Japanese low-fat diet. We studied a group of three men, three women, and three children living in Kyoto and consuming the traditional diet, and in this group we measured the isoflavonoid genistein.2 We found a very high excretion of phyto-oestrogens in urine. The mean values were almost identical in the two groups and especially high excretion was found for genistein (maximum 15.5 Ámol per 24h in a man) and two other isoflavonoids, daidzein and equol (table). All these compounds bind to oestrogen receptors and have weak oestrogenic activity.3 The excretion of the isoflavonoids in urine of the Japanese women was much higher than in American and Finnish women (table) (ref 4 and unpublished data) and as high in children as in middle-aged and old people. These compounds were excreted in 100-fold to 1000-fold higher amounts than those of endogenous oestrogens in normal omnivorous women consuming a western or oriental diet (table).

Urinary isoflavonoid
or oestrogen
Genistein3440 (n = 3)*- - -32.1 (n = 12)
Daidzein2600 (n = 10)*216(n=21)40.5 (n = 12)
Equol2600 (n = 10)*2.8 (n = 21)44.2 (n = 12)
Oestrone (postmenopausal)4.48 (n = 9)**- - -4.48 (n = IO)
Oestradiol (postmenopausal)4.48 (n = 9)- - -0.94 (n = 10)
Oestriol (postmenopausal)4 .48 (n = 9)**- - -4.44 (n = 10)
All assays by gas chromatography/mass spectrometry in selected ion-monitoring mode with deuterated internal standards5, 6 Women collected two to four 72 h urine samples 3-6 months apart and values are thus means of urinary excretion in individual subjects over 6-12 days. Results as geometric means in nmol/24 h.

*Values from ref 2.

**Oriental postmenopausal women (recent immigrants to Hawaii). Same women as in ref 7, but oestrogens measured by new technique.'

The excretion of the isoflavonoids in urine was associated with intake of soy products such as tofu, miso, aburage, atsuage, koridofu, and soybeans. All isoflavonoids are weak oestrogens and such high amounts could have biological effects, especially in post-menopausal women with low oestrogen levels. High levels of isoflavonoid phyto-oestrogens may partly explain why hot flushes and other menopausal symptoms are so infrequent in Japanese women.

Supported by grants from the Medical Research Council, Academy of Finland, and S. Juselius Foundation, Helsinki.

Herman Adlercreutz
Esa Hamalainen

Department of Clinical Chemistry,
University of Helsinki,
SF-00290 Helsinki, Finland

Sherwood Gorbach
Barry Goldin

Nutrition/Infection Unit,
Department of Community Health,
Tufts University School of Medicine.
Boston, Massachusetts. USA

I. Lock, M, Contested Meanings of the Menopause. Lancet 1991; 337:1270-72.

2. Adlercreutz, H., Honjo, H., Higashi, A., et al. Urinary excretion of lignans and isoflavonoid phyto-estrogens in Japanese men and women consuming traditional Japanese diets, Am. J. Clin. Nutr. 1991; 54:1093-100.

3. Setchell K, Adlercreutz, H, Mammalian lignans and phytooestrogens: recent studies on their formaation, metabolism and biological role in health and diseases In: Rowland I. ed. Role of the gut flora in toxicity and cancer. London, Academic Press, 1988. 315-45.

4. Adlercreutz, H, Votsis I, Bannwart C, et al. Determination, of urinary lignans and phytoesogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem 1986; 25: 791-97.

5. Forsis T, Adlercreutz H. The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS-I: quantitation of estrogens after intial hydrolysis of conjugates. J Steroid Biochem 1987; 28: 203-13.

6. Adlercreurz H, Fortsis T, Bannwart C, Wahala K, Brunow G, Hase T, Isotope dilution gas chromatographic-mass spectrometric method for the determination of lignans and isoflavonoids in human urine, including identification of genistein. Clin Chim Acta 1991; 199: 263-53

7. Goldin BR, Adlercreutz H, Gorbach SL, et al. The relationship between estrogen levels and diets of Caucasion and Oriental immigrant women. Am J Clin Nutr 1986; 44: 945-53

Editor's note: These startling findings have since been re-confirmed by further follow-up studies which we shall reproduce or excerpt here later.

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