PLEASE TYPE THE UNIVERSITY OF NEW SOUTH WALES Thesis/Project Report Sheet Surname or Family name: Knight First name: David Other name/s: Charles Abbreviation for degree as given in the U niversity calendar: MD Sc hool: O&G Faculty: Title: lsoflavone Phytoestrogens in Humans. The biological effects at different ages from the clinical perspective. Abstract 350 words maximum: (PLEASE TYPE) In Australia the trend toward dietary change by the general public in an attempt to improve health has resulted in an increased consumption of soy based products containing isoflavones. These compounds are selective oestrogen receptor modulators and have described oestrogen agonist and antagonist effects. The aim of this thesis was to assess the biological effects of isoflavones at different stages of reproductive life in humans. The isoflavone content of different foods, formulas and drinks that may be consumed by infants during their first year of life was investigated by measurement with HPLC in an attempt to define levels of exposure on different feeding regimens. All foods tested contained isoflavones, at varying levels, suggesttng that exposure to these compounds is almost ubiquitous. Given the relatively broad choice of infant foods becoming available, exposure to dietary isoflavones during the first year of life is virtually ubiquitous. The exposure may be higher if soy infant formulas are consumed, however the levels attained appear to fall within normal physiological boundaries. Ovarian follicular fluid was collected during oocyte collection during Assisted Reproduction cycles and examined for the presence of isoflavones by HPLC. Genistein was found to be present in ovarian follicular fluid. This is the first demonstration in humans of the presence of isoflavones of dietary origin in ovarian fluid and the presence of these compounds may effect ovarian function. Supplementation by dietary isoflavones in postmenopausal women was performed to assess the possible effects of isoflavones on estrogen deficiency symptoms and other tissue effects of estrogen deficiency. There was no significant difference in the incidence of vasomotor symptoms between active and placebo groups in three trials conducted. Powdered energy drinks were poorly tolerated and the high withdrawal rate and reporting of side effects suggests that other methods of isoflavone delivery may be more appropriate in the Australian culture. At the doses used no benefit was seen in relief from menopausal symptoms, cardiovascular parameters or bone turnover. 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Any contnbution made to the research by others, with whom I have worked at UNSW or elsewhere, is expliciUy acknowledged in the thesis. ~ I also declare that the intellectual content of this thes.· is the product of my own work, except to the extent that assistance from oth in the projecfs design and conception or in style, presentation and lin · tic ex ression is acknowledged. (Signed) ............. '-1 AI ,L STATRS Bookbinding Ph. !tl2l ·· ..•. >nt., lsoflavone Phytoestrogens in Humans. The biological effects at different ages from the clinical perspective. David C. Knight MB BS, FRANZCOG, GradCert RepodMed City West IVF City West House 12 Caroline St, Westmead, NSW 2145 A thesis submitted for the degree of Doctor of Medicine University of New South Wales January 2001 UNSW 3 0 OCT ?001 LIBRARY I" Abstract In Australia the trend toward dietary change by the general public in an attempt to improve health has resulted in an increased consumption of soy based products containing isoflavones. These compounds are selective oestrogen receptor modulators and have described oestrogen agonist and antagonist effects. The aim of this thesis was to assess the biological effects of isoflavones at different stages of reproductive life in humans. The isoflavone content of different foods, formulas and drinks that may be consumed by infants during their first year of life was investigated by measurement with HPLC in an attempt to define levels of exposure on different feeding regimens. All foods tested contained isoflavones, at varying levels, suggesting that exposure to these compounds is almost ubiquitous. Given the relatively broad choice of infant foods becoming available, exposure to dietary isoflavones during the first year of life is virtually ubiquitous. The exposure may be higher if soy infant formulas are consumed, however the levels attained appear to fall within normal physiological boundaries. 2. Ovarian follicular fluid was collected during oocyte collection during Assisted Reproduction cycles and examined for the presence of isoflavones by HPLC. Genistein was found to be present in ovarian follicular fluid. This is the first demonstration in humans of the presence of isoflavones of dietary origin in ovarian fluid and the presence of these compounds may effect ovarian function. Supplementation by dietary isoflavones in postmenopausal women was performed to assess the possible effects of isoflavones on estrogen deficiency symptoms and other tissue effects of estrogen deficiency. There was no significant difference in the incidence of vasomotor symptoms between active and placebo groups in three trials conducted. Powdered energy drinks were poorly tolerated and the high withdrawal rate and reporting of side effects suggests that other methods of isoflavone delivery may be more appropriate in the Australian culture. At the doses used no benefit was seen in relief from menopausal symptoms, cardiovascular parameters or bone turnover. 3 Publications arising from the work related to this thesis Invited Chapters: Knight DC. Ch 20. Phytoestrogens. In Walker JJ. (Ed) Current Concepts for the Management of the Menopause. In press. Prizes: Best Clinical Research Paper. To be presented at British Fertility Society Annual Conference 2001. Knight DC, Driscoll GL, Tyler JPP. Dietary isoflavones are present in follicular fluid of women. Combined Conference of The Fertility Society of Australia and Australian Society of Reproductive Biology Abs 124, 2000. 4. Papers Knight DC, Tyler JPP, Driscoll GL. Dietary-derived isoflavones are present in ovarian follicular fluid of women. Human Reproduction Submitted Knight DC, Howes JB, Eden JA, Howes LG. The effects and acceptance of isoflavone-containing soy powder dietary supplementation on menopausal symptoms. Climacteric. In press Knight DC, Howes LG. Phytoestrogens or Dietary SERM 1s? Human Reproduction Submitted Hayward CS, Knight DC, Howes JB, Eden JA, Kelly RP. Effect of supplemental isoflavones on large artery function in postmenopausal women. J Hypertension Submitted Knight DC, Howes JB, Eden JA The effect of Promensil™, an isoflavone extract, on menopausal symptoms. Climacteric 1999;2:79- 84. 5 Knight DC, Eden JA, Huang JL, Waring MA. lsoflavone content of infant formulas and other food. J Paediatr Child Health 1998;34: 135- 8. Knight DC, Eden JA. A review of the clinical effects of phytoestrogens. Obstet Gynecol 1996;87:897-904. Knight DC, Lyons Wall PM, Eden JA. A review of phytoestrogens and their effects in relation to menopausal symptoms.[Leading Article] Aust J Nutr Diet 1996;53:5-11. Knight DC, Eden JA, Kelly GE. The phytoestrogen content of infant formulas. [letter] Med J Aust 1996;164:575. Knight DC, Eden JA. Phytoestrogens - a short review. Maturitas 1995;22: 16-75. 6. Abstracts Knight DC, Driscoll GL, Tyler JPP. Dietary isoflavones are present in follicular fluid of women. Combined Conference of The Fertility Society of Australia and Australian Society of Reproductive Biology Abs 124, 2000. Husband AJ, Howes JB, Knight DC et al. The correlation between phenolic estrogen levels and menopause symptoms in women. EEC, COST-916 Phytoestrogens Meeting, Amsterdam, April, 1998. Knight DC, Eden JA,