Increased urinary excretion of 2-hydroxyestrone but not 16α- hydroxyestrone in premenopausal women during a soya diet containing isoflavones

Leejane Lu, Melanie Cree, Shylaja Josyula, Manubai Nagamani, James J. Grady, Karl Anderson

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Abstract

Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17β-estradiol, 4- and 16α-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17β-estradiol to 2- and 16α-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 ± 26 mg/day, mean ± SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ('isoflavone-free'). Urine samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16α-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.918.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (averaged over the entire cycle) from 11.6 ± 2.06 to 17.0 ± 2.96 nmol/12-h (P = 0.03), a 47% increase. However, the mean daily excretion of 16α-hydroxyestrone did not change (7.0 ± 1.14 nmol/12-h during the isoflavone-free and 7.7 ± 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2- hydroxyestrone to 16α-hydroxyestrone was higher during the isoflavone-rich soya diet (2.6 ± 0.34) than during the isoflavone-free diet (2.0 ± 0.32; P = 0.01), a 27% increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17β- estradiol levels and the long-term risk for breast cancer.

Original languageEnglish (US)
Pages (from-to)1299-1305
Number of pages7
JournalCancer Research
Volume60
Issue number5
StatePublished - Mar 1 2000

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Isoflavones
Diet
Genistein
Breast Neoplasms
16-hydroxyestrone
2-hydroxyestrone
Estradiol
Estrogens
Menstrual Cycle
Demography
Urine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Increased urinary excretion of 2-hydroxyestrone but not 16α- hydroxyestrone in premenopausal women during a soya diet containing isoflavones. / Lu, Leejane; Cree, Melanie; Josyula, Shylaja; Nagamani, Manubai; Grady, James J.; Anderson, Karl.

In: Cancer Research, Vol. 60, No. 5, 01.03.2000, p. 1299-1305.

Research output: Contribution to journalArticle

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title = "Increased urinary excretion of 2-hydroxyestrone but not 16α- hydroxyestrone in premenopausal women during a soya diet containing isoflavones",
abstract = "Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17β-estradiol, 4- and 16α-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17β-estradiol to 2- and 16α-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 ± 26 mg/day, mean ± SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ('isoflavone-free'). Urine samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16α-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.918.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (averaged over the entire cycle) from 11.6 ± 2.06 to 17.0 ± 2.96 nmol/12-h (P = 0.03), a 47{\%} increase. However, the mean daily excretion of 16α-hydroxyestrone did not change (7.0 ± 1.14 nmol/12-h during the isoflavone-free and 7.7 ± 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2- hydroxyestrone to 16α-hydroxyestrone was higher during the isoflavone-rich soya diet (2.6 ± 0.34) than during the isoflavone-free diet (2.0 ± 0.32; P = 0.01), a 27{\%} increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17β- estradiol levels and the long-term risk for breast cancer.",
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AU - Lu, Leejane

AU - Cree, Melanie

AU - Josyula, Shylaja

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AU - Grady, James J.

AU - Anderson, Karl

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N2 - Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17β-estradiol, 4- and 16α-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17β-estradiol to 2- and 16α-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 ± 26 mg/day, mean ± SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ('isoflavone-free'). Urine samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16α-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.918.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (averaged over the entire cycle) from 11.6 ± 2.06 to 17.0 ± 2.96 nmol/12-h (P = 0.03), a 47% increase. However, the mean daily excretion of 16α-hydroxyestrone did not change (7.0 ± 1.14 nmol/12-h during the isoflavone-free and 7.7 ± 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2- hydroxyestrone to 16α-hydroxyestrone was higher during the isoflavone-rich soya diet (2.6 ± 0.34) than during the isoflavone-free diet (2.0 ± 0.32; P = 0.01), a 27% increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17β- estradiol levels and the long-term risk for breast cancer.

AB - Asian diets high in soy are associated with lower risk for breast cancer compared with Western diets. Moreover, higher levels of two putative carcinogenic metabolites of 17β-estradiol, 4- and 16α-hydroxyestrogen, and lower amounts of anticarcinogenic metabolites, 2-hydroxyestrogens, have been associated with greater breast cancer risk. In this study, we tested the hypothesis that consumption of a soya diet containing the weakly estrogenic isoflavones genistein and daidzein may alter the metabolism of 17β-estradiol to 2- and 16α-hydroxylated products. Eight premenopausal women were placed on a soya-containing, constant diet in a metabolic unit. The diet provided 400 kilocalories from soymilk and 113-202 mg/day (158 ± 26 mg/day, mean ± SD) isoflavones daily for a complete menstrual cycle. After a washout period of 4 months, the subjects consumed the same diet, but with soymilk that contained <4.5 mg/day isoflavones ('isoflavone-free'). Urine samples were collected for 24 h daily for the entire cycle during each soya diet period for the analysis of daidzein, genistein, and 2- and 16α-hydroxyestrone. Subjects excreted measurable amounts of daidzein (11.6-39.2 mg/day) and genistein (2.918.2 mg/day) during the isoflavone-rich soya diet but not during the isoflavone-free soya diet. The diet rich in isoflavones increased the cycle mean daily urinary excretion of 2-hydroxyestrone (averaged over the entire cycle) from 11.6 ± 2.06 to 17.0 ± 2.96 nmol/12-h (P = 0.03), a 47% increase. However, the mean daily excretion of 16α-hydroxyestrone did not change (7.0 ± 1.14 nmol/12-h during the isoflavone-free and 7.7 ± 1.25 nmol/12-h during the isoflavone-rich diet; P = 0.36). The ratio of 2- hydroxyestrone to 16α-hydroxyestrone was higher during the isoflavone-rich soya diet (2.6 ± 0.34) than during the isoflavone-free diet (2.0 ± 0.32; P = 0.01), a 27% increase. These results suggest that soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, and this may play an important role in lowering 17β- estradiol levels and the long-term risk for breast cancer.

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