1. Annette Thomas, RN, MS, PhD student Nancy Fugate Woods, PhD, RN, FAAN Ellen Sullivan Mitchell, PhD Janet Schnall MS, AHIIP Soy, Isoflavones, and Amino Acids for Symptom Clusters During the Menopausal Transition and Early Postmenopause: A Systematic Review

2. Background Women have been reluctant to use HT since the publication of the WHI results and increasingly have become interested in CAM therapies Soy & Isoflavones may be a good alternative for women who experience Hot Flashes as well as other associated symptoms such as problems with cognition, sleep, mood, or pain.

3. Background SoyIsoflavones Transformed by intestinal flora during digestion Phytoestrogen Regulates the estrogen levels in the body 30% of population can convert Diadzein into EQUOL Diadzein Genistein Glyceiti n

4. Aim To review controlled clinical trials of Soy, Isoflavones, and Amino Acids on hot flashes and at least one other symptom that women experience during the menopausal transition (MT) and post menopause (PM) such as problems with sleep, cognitive function, mood, and pain

5. Methods Of the 59 unique trials identified of nonpharmacologic therapies, 17 Soy, Isoflavone, & Amino Acid RCTs were systematically reviewed: 5 Soy protein 7 Isoflavone 2 Amino Acid 3 Mixtures

6. Results… Soy Protein StudyIntervention/ComparisonHot Flash SleepCog - fxn MoodPain Basaria 2009 20g soy protein vs. 20g whole milk protein NSNMNS+NM Hanachi 2008 12.5g soy protein in soymilk vs. soymilk + walking 1 hour ?NS Jou 2008 6g soy germ extract vs. roasted wheat +NSNMNS Welty 2007 25g soy protein (soy nuts) vs. TLC diet (low cholesterol) +NM + Lewis 2006 25g soy in soy flour muffins vs. ground flaxseed muffings vs. wheat flour muffins NSNM

7. Results… Isoflavones StudyIntervention/ComparisonHot Flashes Slee p Cog- fxn MoodPain Evans 2011 Synthetic Genistein (30mg) vs. Placebo +NM NSNM Carmignani 2010 Isoflavone powder (90mg) vs. HT vs. placebo +NM ++ Lee 2010 Rexflavone (135mg) vs. placebo ++NMNS+ Albertazzi 2005 Genistein (90mg) vs. placebo+ (HF>9) NSNMNSNM

8. Results… Isoflavones (cont’d) StudyIntervention/ComparisonHot Flashes SleepCog- fxn MoodPain Hildago 2005 Red Clover Isoflavone (80mg) vs. placebo +++++ Jou 2005 70mg isoflavone vs. 35mg isoflavone vs. placebo NS+NM+ Uesugi 2004 40mg isoflavone vs. placeboNS NMNS Key: + is significant for P<=0.05 or better NS is Not Significant NM is Not Measured

9. Results… Amino Acids StudyIntervention/ComparisonHot Flashes SleepCog- fxn MoodPain Guttoso 2009 Methionine 2g vs. placeboNS NM Guttoso 2008 L-Isoleucine 5mg vs. placeboNS NM

10. Results… Mixtures StudyIntervention/ComparisonHot Flashes SleepCog- fxn MoodPain Ishiwata 2009 10mg EQUOL vs 30mg EQUOL vs. placebo (EP vs. Non-EP) NSNM + (N-30) NM Mucci 2006 Magnolia Bark Extract 60mg + Magnesium 50mg + Calcium+ Vitamin D vs. Calcium + Vitamin D NS+NM+ Secreto 2003 80mg isoflavones + 3mg melatonin vs. 80mg isoflavones vs. 3mg melatonin vs. placebo + (Iso- flavones alone) NS Key: EP= Equol producers, Non-EP= Non Equol Producers, N-30= Non Equol Producers taking 30mg Equol

11. Conclusion Of all the studies, Rexflavone (135mg) demonstrated significant treatment effects for all categories The soy protein category showed significant treatment effects for hot flashes and mood symtpoms Isoflavones significantly improved hot flashes, sleep, mood, and pain symptoms Of the symptoms studied, soy and isoflavone therapies most frequently improved hot flashes and mood and had the least effect on cognitive functions Recommendations for future research is to include symptom cluster categories, more cognitive function studies, and classification into EP vs. Non-EP women.

12. Acknowledgement The Nursing Scholarship Foundation of The University of Washington School of Nursing Data were collected with support from grants from the National Institute for Nursing Research, NIH, NR01 04141 and NINR, NIH, P50-NR-02323, P30-NR04001

13. Thank You