Endocrine status in normal British, Japanese and Hawaiian-Japanese women

Hayward, John; Greenwood, F. C.; Glober, Gary A.; Stemmerman, Grant N.; Bulbrook, R. D.; Wang, D.Y.; Kumaokas, S.

doi:10.1016/0014-2964(78)90228-1

Cited by 37 publications

(19 citation statements)

References 30 publications

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“…This could imply that postmenopausal breast cancer might be the result of prolonged hormonal and environmental factors. This would be consistent with the report of Hayward et al (1978) that the lower incidence of breast cancer in post-menopausal Japanese women, living in Japan, compared to Western women, and the rise in incidence in migratory Japanese women is reflected in the levels of serum DS. It is possible, therefore, that low urinary androgen metabolites predict a high risk of early onset breast cancer, and that high levels are associated with an increased risk in the late, or post-menopausal, disease.…”

Section: Discussionsupporting

confidence: 93%

True

et al. 2000

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It would be very useful if it were possible to identify, within an apparently normal population, those who will develop breast cancer. Although this can be achieved by genetic testing for mutations of BRCA1 and BRCA2, such susceptibility genes are involved in the aetiology of only about 5% of breast cancer cases (Lynch and Lynch, 1986). By contrast, events related to a woman's menstrual and reproductive history, which have been widely recognized as determinants of breast cancer incidence, are not impressive predictors of individual risks. Such poor predictive performance could result from these epidemiological variables being only manifestations of other underlying factors. Indeed the size of the effects of the menstrual and reproductive variables and the observation that breast cancer rates change over a woman's life have stimulated investigation of endogenous sex hormones as potential causes underlying these observed effects (Key and Pike, 1988;Toniolo et al, 1995;Key et al, 1996). Methodological issues related to hormone measurements, however, complicate the study of their relationship with breast cancer. Furthermore, there is no general consensus regarding which biological forms of these hormones are actually associated with the observed changes in incidence rates.The role of steroids in the aetiology of breast cancer is uncertain. Extensive analysis of the scientific literature shows a highly significant increase in blood oestradiol levels in post-menopausal women with breast cancer (Thomas et al, 1997). The position of oestrogens and premenopausal women is uncertain (Key and Pike, 1988; Thomas et al, 1997). Androgens have been studied less extensively than oestrogens and no meta-analysis has yet been undertaken.The first prospective study in this field was performed by Bulbrook and Hayward who showed that levels of androsterone (A) and aetiocholanolone (E) were abnormally low in women who subsequently developed breast cancer (Bulbrook and Hayward, 1967;Bulbrook et al, 1971). Most of the cases were premenopausal and the abnormality was present up to 11 years before the clinical diagnosis of the disease, suggesting that high levels of androgen metabolites might have a protective effect, at least in younger women. However, other mainly retrospective casecontrol studies have claimed that high androgen excretion is positively associated with breast cancer risk (e.g. Secreto and Zumoff, 1994). Such contrasting results could be reconciled if the effects of androgens depended on menopausal status. This would occur if the androgens acted as oestrogen inhibitors in premenopausal women and as oestrogen enhancers (or even oestrogens) in the postmenopausal (Secreto and Zumoff, 1994;Adams, 1998 Summary Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1...

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Section: Discussionsupporting

confidence: 93%

True

et al. 2000

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“…There are few other data on blood hormone levels in postmenopausal Japanese women compared to American or Western European white women. Hayward et al (1978) found no difference between the postmenopausal plasma El levels of British women (n = 30) and of Japanese women in Tokyo (n = 29), and plasma E2 levels were 11% lower in the British women. Goldin et al (1986) also found no differences in plasma El levels between American white (n = 10) and Asian women who had recently immigrated to Hawaii (n = 8); they did, however, find a three-fold increase in E2 levels in the American women.…”

Section: Discussionmentioning

confidence: 73%

“…It is, therefore, important that the discrepancy between these results and those of Hayward et al (1978) be resolved. Further studies of relevant populations need to be done.…”

Section: Discussionmentioning

confidence: 95%

“…In designing these studies, it is important to realise that the primary aim is to establish whether hormone levels in Asian women living in a traditional way are lower than the levels in the West. Studies of urbanised Asian women may not be addressing the relevant question; it may be that the reason that Hayward et al (1978) failed to find lower oestrogen levels was because their subjects appear to have been middle-class Tokyo women. There is still much to be learned from studies of the relationship of diet, exercise and other factors to oestrogen metabolism.…”

Section: Discussionmentioning

confidence: 99%

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Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan

Shimizu

Ross²,

Bernstein³

et al. 1990

Br J Cancer

156

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Summary Serum oestrone (El), oestradiol (E2) and sex hormone binding globulin (SHBG) levels were studied in postmenopausal Japanese women in Japan (n = 91) and postmenopausal American white women (n = 38). The Japanese women were deliberately chosen to be from a rural agricultural area in order to get samples which represent as closely as possible the traditional Japanese 'lifestyle' that gave rise to the low rates of breast cancer in Japan. El levels were 47%, and E2 levels 36%, greater in the American women; these differences were only reduced to 43% and 27% after adjustment for the lower weight of the Japanese. These results were all statistically highly significant. There was little difference in SHBG levels between the Japanese and the American women. These results for El and E2 could be an important part of the explanation why Japanese and American breast cancer rates continue to diverge further after the menopause.There is considerable evidence that oestrogens are involved in the aetiology of breast cancer and that increased blood levels of oestrogen in postmenopausal breast cancer patients are one marker of high risk (Key & Pike, 1988;Bernstein et al., 1990). The incidence rates for breast cancer in Japan are substantially lower than those in the USA and European countries (Muir et al., 1987), and some systematic pathological and clinical differences between breast cancer diagnosed in Japan and western countries have been reported (Wynder et al., 1963;Chabon et al., 1974). These observations suggest that there may be important differences in endocrine function among residents in these areas, but there are surprisingly few data on blood hormone levels in healthy populations from these countries. We report here a study comparing serum oestrogen and sex-hormone-binding globulin (SHBG) levels of post-menopausal Japanese women in Japan to those of white women in the USA. Subjects and methodsThe Japanese subjects were volunteers residing in rural areas of Miyagi, a prefecture in north-east Japan. These women were mainly from rice farming families. We first contacted them at a general medical screening clinic for the healthy elderly sponsored by their farmer's union, informing them of the purpose of our study and asking for their cooperation. The subjects in the USA were American non-Latino volunteers from a retirement community in Southern California, who had a blood sample drawn during a well-patient visit to a local health clinic. All women had to have intact ovaries, be postmenopausal, and be 60 to 70 years of age. Ninety-one women were sampled in Japan; 38 women were sampled in California. Women with any past or present endocrine disease, or who had used steroid hormones during the previous 12 months, or had more than 12 months total use of steroid hormones, were excluded.All subjects were asked to provide information on a series of factors related to breast cancer risk and, possibly, to hormonal status, including ages at menarche, menopause, and first full-term pregnancy, number of children, and present h...

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“…For example, British women aged 35-44, have been found to have oestradiol concentrations 36% higher on average than those of Chinese women of the same age (Key et al, 1990). Comparisons of premenopausal Western women with Asian women living in Japan (MacMahon et al, 1974;Hayward et al, 1978;Gray et al, 1982) or China (Bernstein et al, 1990), or recent migrants to Hawaii (Goldin et al, 1986), have also, in general, found lower oestrogen levels in the group of women at lower risk of breast cancer. In post-menopausal women it has been found that American whites have oestradiol levels three times those of recent Asian migrants to Hawaii (Goldin et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Effects of a low-fat high-carbohydrate diet on plasma sex hormones in premenopausal women: results from a randomized controlled trial

Boyd

Lockwood²,

Greenberg³

et al. 1997

Br J Cancer

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Summary We are conducting a long-term randomized controlled trial to determine if intervention with a low-fat high-carbohydrate diet reduces breast cancer risk. The present study examines the effects of 2 years of dietary intervention on serum sex hormone levels in premenopausal women. Subjects with extensive mammographic densities were enrolled in a dietary intervention trial. The intervention involved intensive individual counselling aimed at reducing total dietary fat to 15% of calories. Control subjects received general advice about diet but were not counselled to change their fat intake. Serum sex hormone levels were measured in 220 premenopausal subjects at entry and 2 years after randomization. Two years after randomization oestradiol levels were 20% (70 pmol 1-1) lower (P = 0.04) and progesterone levels were 35% (1.0 nmol 1-1) lower (P = 0.004) and follicle-stimulating hormone (FSH) levels were 7% (1 IU) higher (P = 0.38) in the intervention group than in the control group. The FSH-oestradiol ratio was 13% higher in the intervention group (P= 0.18). Samples analysed accounting for the timing of the blood sample in relation to the menstrual cycle showed that, in the intervention group, oestradiol and progesterone levels were lower and FSH levels higher in subjects with blood samples taken more than 30 days after the last menstrual period.Because of the strong evidence linking ovarian hormonal activity to breast cancer risk, these results suggest that a low-fat high-carbohydrate diet may reduce risk of breast cancer by reducing exposure to ovarian hormones that are a stimulus to cell division in the breast.

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Endocrine status in normal British, Japanese and Hawaiian-Japanese women

Cited by 37 publications

References 30 publications

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Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan

Effects of a low-fat high-carbohydrate diet on plasma sex hormones in premenopausal women: results from a randomized controlled trial

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