Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial원문보기
BACKGROUND/OBJECTIVES: Soy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone bi...
BACKGROUND/OBJECTIVES: Soy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women. SUBJECTS/METHODS: A randomized, double-blind study design was used. Eighty-seven participants who had undergone natural menopause were randomly administered either 70 mg/day isoflavones (n = 43) or placebo (n = 41) for 12 weeks. We assessed the Kupperman index for climacteric symptoms and the menopause-specific quality of life (MENQOL) questionnaire for quality of the life. Biomarkers of bone metabolism were also measured in serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N- and C-terminal cross-linking telopeptides of type Ι collagen (NTx, CTx), and urine-deoxypyridinolin (u-DPD). RESULTS: Scores of the Kupperman index were decreased in both the isoflavones group ($-7.0{\pm}15.8$, P = 0.0074) and placebo group ($-6.3{\pm}14.6$, P = 0.0064) during the intervention, but no significant difference was noted between the groups. Regarding the bone formation markers, the level of serum BALP increased by $6.3{\pm}4.1%$ (P = 0.004) and OC increased by $9.3{\pm}6.2%$ (P < 0.001), meanwhile those of the placebo were not changed. For the bone resorption markers, NTx, CTx, and u-DPD were not significantly different in either group. MENQOL was significant decreased in the isoflavone group ($-0.6{\pm}0.5$) and placebo group ($-0.6{\pm}0.4$), with a significant difference between groups (P = 0.0228). CONCLUSIONS: Our study suggests that 70 mg isoflavones supplement has beneficial effects on bone formation markers; however, it showed no benefit compared to the placebo on climacteric symptoms or quality of life.
BACKGROUND/OBJECTIVES: Soy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women. SUBJECTS/METHODS: A randomized, double-blind study design was used. Eighty-seven participants who had undergone natural menopause were randomly administered either 70 mg/day isoflavones (n = 43) or placebo (n = 41) for 12 weeks. We assessed the Kupperman index for climacteric symptoms and the menopause-specific quality of life (MENQOL) questionnaire for quality of the life. Biomarkers of bone metabolism were also measured in serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N- and C-terminal cross-linking telopeptides of type Ι collagen (NTx, CTx), and urine-deoxypyridinolin (u-DPD). RESULTS: Scores of the Kupperman index were decreased in both the isoflavones group ($-7.0{\pm}15.8$, P = 0.0074) and placebo group ($-6.3{\pm}14.6$, P = 0.0064) during the intervention, but no significant difference was noted between the groups. Regarding the bone formation markers, the level of serum BALP increased by $6.3{\pm}4.1%$ (P = 0.004) and OC increased by $9.3{\pm}6.2%$ (P < 0.001), meanwhile those of the placebo were not changed. For the bone resorption markers, NTx, CTx, and u-DPD were not significantly different in either group. MENQOL was significant decreased in the isoflavone group ($-0.6{\pm}0.5$) and placebo group ($-0.6{\pm}0.4$), with a significant difference between groups (P = 0.0228). CONCLUSIONS: Our study suggests that 70 mg isoflavones supplement has beneficial effects on bone formation markers; however, it showed no benefit compared to the placebo on climacteric symptoms or quality of life.
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제안 방법
All investigators, research staff, and subjects were blinded to the treatment codes. After the baseline visit, women returned at the inter-visit (6 weeks) and final visit (12 weeks) to complete surveys on Kupperman index and menopause-specific quality of life (MENQOL) and for monitoring of adverse effects. Subjects were required to discontinue the use of other dietary and herbal supplements and minimized the intake of food sources of isoflavones < 10 mg/day, which were monitored by 3-day food diaries.
1. Diagram of participant flow in postmenopausal Korean women divided into a 70 mg/day isoflavones group and a placebo group for 12 weeks. This study was analysis for intent to treat: Placebo (n = 43), Isoflavones (n = 41)
At the screening visit (-1 week), postmenopausal women provided written informed consent and were assessed for eligibility through a screening mammogram and clinical blood chemistry measures. Individual information was collected by trained interviewers via face-to-face interview based on structured questionnaires on sociodemographic data, medical history, medications, dietary habits, and physical activity. At the baseline visit (0 week), postmenopausal women who met the study criteria were randomly assigned to either the isoflavones or placebo group.
This study was a randomized, double-blind, controlled clinical trial performed over 12 weeks. The study protocol was approved by the Kyung Hee University Hospital Ethnic Committee (Seoul, South Korea) (No: KMC IRB 1002-02).
대상 데이터
Eligible subjects were postmenopausal women with mild menopausal symptoms aged 45-60 years, with BMI ranging from 19.0 to 30.0 kg/m2. Postmenopause was defined as a last menstrual period > 12 months ago prior and serum folliclestimulating hormone (FSH) level > 40 IU/mL.
Of the 113 women considered for the study, 25 were excluded due to a serum level of FSH less than 40 IU/mL and 1 for withdrawal of consent. Of the 87 postmenopausal women randomized into the trial, 1 in the placebo group and 2 in the isoflavones group did not reach the end of the trial; hence, there were 43 in the placebo group and 41 in the isoflavones group with at least baseline data available for analysis.
데이터처리
† P-values were estimated using Student’s t-test or § repeated measures ANOVA and Bonferroni’s post hoc test.
The categorical variables of the two groups were compared with the Chi-square test, and the data are presented as percentage (%) or number (n). For non-parametric data, the distribution of variables was assessed using the KolmogorovSmirnov or Shapiro-Wilk tests for normality and the F-test for homogeneity of variances. When allowed by data distribution and homogeneity of variances, the independent or paired t-test was performed to evaluate the significance between groups or within a group.
In addition, repeated-measures ANOVA was performed to test the significant group × time effects of isoflavones on menopausal symptoms and MENQOL scores during the treatment period.
For non-parametric data, the distribution of variables was assessed using the KolmogorovSmirnov or Shapiro-Wilk tests for normality and the F-test for homogeneity of variances. When allowed by data distribution and homogeneity of variances, the independent or paired t-test was performed to evaluate the significance between groups or within a group. In addition, repeated-measures ANOVA was performed to test the significant group × time effects of isoflavones on menopausal symptoms and MENQOL scores during the treatment period.
이론/모형
In addition, repeated-measures ANOVA was performed to test the significant group × time effects of isoflavones on menopausal symptoms and MENQOL scores during the treatment period. The Bonferroni test was used for post hoc multiple comparisons. A two-tailed P-value less than 0.
4 mg genistin. The components of the isoflavones were analyzed and labeled using high-performance liquid chromatographic (HPLC) methods [23]. In Korea, there is no defined isoflavones dosage for improving menopausal symptoms and health outcomes.
성능/효과
1) Kupperman index was used to evaluate the overall climacteric symptoms based on the presence of 25 items: normal 40 total score.
2) Menopausal-specific quality of life questionnaire consists of 29 items divided into four domains: vasomotor (3 items), psychosocial (7 items), physical (16 items), and sexual (3 items) on quality of life in postmenopausal women.
2) Menopausal-specific quality of life questionnaire was developed as a condition-specific, self-completed, outcome tool to assess the impact of this life event and to evaluate interventions. It consists of 29 items divided into four domains: vasomotor (3 items), psychosocial (7 items), physical (16 items), and sexual (3 items) on quality of life in postmenopausal women.
Interestingly, the Kupperman index score at 6 weeks in the isoflavones group was significantly decreased, while that in the placebo group did not change. After 12 weeks, both the isoflavones and placebo groups showed a significant decrease in Kupperman index. Also, isoflavones increased the levels of the serum bone formation markers, BALP and OC, in line with previous results.
After 12 weeks, the bone formation markers BALP and OC significantly increased by 6.3 ± 4.1% (P = 0.004) and 9.3 ± 6.2%, respectively.
In accordance with our results, soy protein 40 g (approximately 118 mg/day of isoflavones) for 12 weeks resulted no significant differences with a placebo group in u-DPD concentration (Isoflavones:-0.8 ± 0.9 vs. Placebo:-0.3 ± 0.7 nmol/ mmol Cr, P = 0.40) [38].
Also, isoflavones increased the levels of the serum bone formation markers, BALP and OC, in line with previous results. MENQOL decreased at 6 and 12 weeks in both groups, and there was a significant different between groups, with changes in the placebo group being greater than those in the isoflavones group.
No significant difference was noted in overall average MENQOL score between groups at baseline (isoflavones group:1.0 ± 0.6 and placebo: 1.3 ± 0.8).
후속연구
Another limitation is that the Kupperman index and MENQOL questionnaire are self-reporting questionnaires; women were asked to provide some retrospective information such as climacteric symptoms experienced in the preceding weeks; thus recall bias was unavoidable. Finally, we did not measure serum isoflavones changes, which should be analyzed in a further study as a compliance indicator.
참고문헌 (46)
1 Han KK Soares JM Jr Haidar MA de Lima GR Baracat EC Benefits of soy isoflavone therapeutic regimen on menopausal symptoms Obstet Gynecol 2002 99 389 394 11864664
2 Nahas EA Nahas-Neto J Orsatti FL Carvalho EP Oliveira ML Dias R Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study Maturitas 2007 58 249 258 17913408
5 Cancellieri F De Leo V Genazzani AD Nappi C Parenti GL Polatti F Ragni N Savoca S Teglio L Finelli F Nichelatti M Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts Maturitas 2007 56 249 256 17275225
6 Evans M Elliott JG Sharma P Berman R Guthrie N The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebo-controlled study Maturitas 2011 68 189 196 21163595
7 Yamori Y Moriguchi EH Teramoto T Miura A Fukui Y Honda KI Fukui M Nara Y Taira K Moriguchi Y Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study J Am Coll Nutr 2002 21 560 563 12480802
8 Murkies AL Lombard C Strauss BJ Wilcox G Burger HG Morton MS Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat Maturitas 1995 21 189 195 7616867
9 Washburn S Burke GL Morgan T Anthony M Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women Menopause 1999 6 7 13 10100174
10 Alekel DL Germain AS Peterson CT Hanson KB Stewart JW Toda T Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women Am J Clin Nutr 2000 72 844 852 10966908
11 Wangen KE Duncan AM Merz-Demlow BE Xu X Marcus R Phipps WR Kurzer MS Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women J Clin Endocrinol Metab 2000 85 3043 3048 10999783
12 Dennerstein L Dudley EC Hopper JL Guthrie JR Burger HG A prospective population-based study of menopausal symptoms Obstet Gynecol 2000 96 351 358 10960625
13 Levis S Strickman-Stein N Ganjei-Azar P Xu P Doerge DR Krischer J Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial Arch Intern Med 2011 171 1363 1369 21824950
14 Dodin S Lemay A Jacques H Légaré F Forest JC Mâsse B The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial J Clin Endocrinol Metab 2005 90 1390 1397 15613422
15 Khaodhiar L Ricciotti HA Li L Pan W Schickel M Zhou J Blackburn GL Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women Menopause 2008 15 125 132 18257146
16 Nelson HD Vesco KK Haney E Fu R Nedrow A Miller J Nicolaidis C Walker M Humphrey L Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis JAMA 2006 295 2057 2071 16670414
18 de Kleijn MJ van der Schouw YT Wilson PW Adlercreutz H Mazur W Grobbee DE Jacques PF Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study(1-4) J Nutr 2001 131 1826 1832 11385074
19 Keinan-Boker L Peeters PH Mulligan AA Navarro C Slimani N Mattisson I Lundin E McTaggart A Allen NE Overvad K Tjønneland A Clavel-Chapelon F Linseisen J Haftenberger M Lagiou P Kalapothaki V Evangelista A Frasca G Bueno-de-Mesquita HB van der Schouw YT Engeset D Skeie G Tormo MJ Ardanaz E Charrondière UR Riboli E Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study Public Health Nutr 2002 5 1217 1226 12639228
20 Chun OK Chung SJ Song WO Estimated dietary flavonoid intake and major food sources of U.S. adults J Nutr 2007 137 1244 1252 17449588
21 National Research Institute of Health (KR) Clinical Research Information Service [Internet] Cheongju National Research Institute of Health cited 2015 December 30 Available from: https://cris.nih.go.kr/cris/index.jsp
22 Petri Nahas E Nahás Neto J De Luca L Traiman P Pontes A Dalben I Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy Maturitas 2004 48 372 380 15283929
23 Association of Official Analytical Chemists (US) Official Methods of Analysis of AOAC International 18th ed Gaithersburg (MD) AOAC International 2005
24 Food Safety Commission of Japan Fundamental concepts in the safety assessment of foods containing soy isoflavones for the purpose of specified health use, in Japanese [Internet] Tokyo Food Safety Commission of Japan 2006 cited 2015 June 6 Available from: http://www.fsc.go.jp/sonota/daizu_isoflavone.html
25 Lee SK Lee MJ Yoon S Kwon DJ Estimated isoflavone intake from soy products in Korean middle-aged women J Korean Soc Food Sci Nutr 2000 29 948 956
26 Bhagwat S Haytowitz DB Holden JM USDA database on the isoflavone content of selected food: release 2.0 [Internet] Beltsville (MD) U.S. Department of Agriculture 2008 cited 2015 August 14 Available from: https://www.ars.usda.gov/ARSUserFiles/80400525/Data/isoflav/Isoflav_R2.pdf
27 Wakai K Egami I Kato K Kawamura T Tamakoshi A Lin Y Nakayama T Wada M Ohno Y Dietary intake and sources of isoflavones among Japanese Nutr Cancer 1999 33 139 145 10368808
28 Kim MS Lee YS A study on the menopause management practice and the quality of life in climacteric women J Korean Soc Matern Child Health 1999 3 75 87
29 Hilditch JR Lewis J Peter A van Maris B Ross A Franssen E Guyatt GH Norton PG Dunn E A menopause-specific quality of life questionnaire: development and psychometric properties Maturitas 1996 24 161 175 8844630
30 Moher D Schulz KF Altman DG The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials Lancet 2001 357 1191 1194 11323066
31 Ye YB Wang ZL Zhuo SY Lu W Liao HF Verbruggen M Fang S Mai HY Chen YM Su YX Soy germ isoflavones improve menopausal symptoms but have no effect on blood lipids in early postmenopausal Chinese women: a randomized placebo-controlled trial Menopause 2012 19 791 798 22278344
32 Taku K Melby MK Kronenberg F Kurzer MS Messina M Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials Menopause 2012 19 776 790 22433977
33 Taku K Melby MK Kurzer MS Mizuno S Watanabe S Ishimi Y Effects of soy isoflavone supplements on bone turnover markers in menopausal women: systematic review and meta-analysis of randomized controlled trials Bone 2010 47 413 423 20452475
34 Morabito N Crisafulli A Vergara C Gaudio A Lasco A Frisina N D'Anna R Corrado F Pizzoleo MA Cincotta M Altavilla D Ientile R Squadrito F Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study J Bone Miner Res 2002 17 1904 1912 12369794
36 Kanno S Hirano S Kayama F Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells Toxicology 2004 196 137 145 15036763
37 Sugimoto T Nishiyama K Kuribayashi F Chihara K Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures J Bone Miner Res 1997 12 1272 1279 9258758
38 Dalais FS Ebeling PR Kotsopoulos D McGrath BP Teede HJ The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women Clin Endocrinol (Oxf) 2003 58 704 709 12780746
39 Védrine N Mathey J Morand C Brandolini M Davicco MJ Guy L Rémésy C Coxam V Manach C One-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women Eur J Clin Nutr 2006 60 1039 1045 16482068
40 Thomas AJ Ismail R Taylor-Swanson L Cray L Schnall JG Mitchell ES Woods NF Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review Maturitas 2014 78 263 276 24951101
41 Wu J Oka J Higuchi M Tabata I Toda T Fujioka M Fuku N Teramoto T Okuhira T Ueno T Uchiyama S Urata K Yamada K Ishimi Y Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial Metabolism 2006 55 423 433 16546471
42 Hall WL Vafeiadou K Hallund J Bügel S Koebnick C Reimann M Ferrari M Branca F Talbot D Dadd T Nilsson M Dahlman-Wright K Gustafsson JA Minihane AM Williams CM Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production Am J Clin Nutr 2005 82 1260 1268 16332659
43 Tousen Y Ezaki J Fujii Y Ueno T Nishimuta M Ishimi Y Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial Menopause 2011 18 563 574 21252728
44 Loprinzi CL Sloan J Stearns V Slack R Iyengar M Diekmann B Kimmick G Lovato J Gordon P Pandya K Guttuso T Jr Barton D Novotny P Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis J Clin Oncol 2009 27 2831 2837 19332723
45 U.S. Food and Drug Administration Guidance for industry estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms: recommendations for clinical evaluation [Internet] Rockville (MD) U.S. Food and Drug Administration 2003 cited 2014 July 20 Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071643.pdf
46 Enck P Klosterhalfen S Zipfel S Novel study designs to investigate the placebo response BMC Med Res Methodol 2011 11 90 21663609
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