Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.Am J Clin Nutr. 1998;68(6 Suppl):1375S-1379S. doi:10.1093/ajcn/68.6.1375S

Publication Date: 1998

Peer Reviewed: Yes

Study Design: 6-mo, parallel-group, double-blind trial with 3 interventions

Methodology: 66 hypercholesterolemic, postmenopausal women randomly assigned to three groups: Step I diet with 40 g protein/d from casein and nonfat dry milk (CNFDM), Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56), or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein (ISP90); total and regional bone mineral content and density assessed; blood lipid profiles, mononuclear cell LDL receptor mRNA analyzed

Sample Size: 66 hypercholesterolemic, postmenopausal women

Controls Used: Casein and nonfat dry milk (CNFDM)

Dose Used: 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56) or 2.25 mg isoflavones/g protein (ISP90)

Statistical Significance Declared: Non-HDL cholesterol for both ISP56 and ISP90 groups reduced compared with the CNFDM group (P < 0.05); HDL cholesterol increased in both ISP56 and ISP90 groups (P < 0.05); mononuclear cell LDL receptor mRNA increased in ISP56 or ISP90 groups compared with CNFDM (P < 0.05); significant increases in bone mineral content and density in the lumbar spine for ISP90 group compared with the control group (P < 0.05)

Adverse Events: Not specifically mentioned in the provided text

Conflict of Interest: "Supported by the Illinois Soybean Program Operating Board and Protein Technologies International, St Louis."

Hooper, L., Ryder, J. J., Kurzer, M. S., Lampe, J. W., Messina, M. J., Phipps, W. R., & Cassidy, A. (2009). Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis. *Human Reproduction Update*, 15(4), 423-440. doi:10.1093/humupd/dmp010

Publication Date: Published online March 19, 2009

Peer Reviewed: Yes

Study Design: Systematic review and meta-analysis

Methodology: Searched databases of MEDLINE, EMBASE, Cochrane Library, and other sources to December 2007; included randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on various hormones in women.

Sample Size: Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included.

Controls Used: Usual diet or usual diet with placebo soy/isoflavone

Dose Used: Various isoflavone-rich soy products with markedly varying isoflavone content

Statistical Significance Declared: Reductions in FSH (by 22%, P = 0.01) and LH concentrations (by 24%, P = 0.05), and an increase in menstrual cycle length of 1.05 days (95% CI 0.13 to 1.97, I2 0%, 10 studies)

Adverse Events: Gastrointestinal side effects, but not dropouts due to adverse effects or any recorded side effect, were statistically significantly more likely to occur in participants taking any source of soy and/or isoflavones than controls.

Conflict of Interest: This work was partially funded by the Soy Nutrition Institute, Inc., St Louis, MO, USA. M.J.M. consults for companies that manufacture and/or sell soyfoods, soy protein and isoflavone supplements and is a Scientific Advisory Board Member of the Soy Nutrition Institute.

Kurzer MS. Soy consumption for reduction of menopausal symptoms. Inflammopharmacology. 2008;16(5):227-229. doi:10.1007/s10787-008-8021-z

Publication Date: Published Online First 26 September 2008

Peer Reviewed: Yes

Study Design: Systematic review and meta-analysis

Methodology: The Cochrane Library, MEDLINE, and EMBASE were searched until December 2007. Included randomised or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone, and thyroid hormones in women.

Sample Size: One recent meta-analysis of 12 randomised, controlled trials; a second critical review of 11 studies.

Controls Used: Placebo

Dose Used: Various isoflavone-rich soy products with markedly varying isoflavone content

Statistical Significance Declared: Reductions in FSH (by 22%, P = 0.01) and LH concentrations (by 24%, P = 0.05), and an increase in menstrual cycle length of 1.05 days (95% CI 0.13 to 1.97, I2 0%, 10 studies)

Adverse Events: Gastrointestinal side effects, but not dropouts due to adverse effects or any recorded side effect, were statistically significantly more likely to occur in participants taking any source of soy and/or isoflavones than controls.

Conflict of Interest: No conflict of interest.

Somekawa Y, Chiguchi M, Ishibashi T, Aso T. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstetrics & Gynecology. 2001;97(1):109-115. doi:10.1016/S0029-7844(00)01080-2

Publication Date: Available online 4 January 2001

Peer Reviewed: Yes

Study Design: "To evaluate the effects of dietary isoflavones in soy products on menopausal symptoms, lipid profiles, and bone mineral densities in postmenopausal Japanese women."

Methodology: Estimated daily intakes of isoflavones in the diets of 478 postmenopausal Japanese women; recorded serum values of fasting total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and apolipoproteins; measured bone mineral density at the lumbar spine (L2–L4) by dual energy x-ray absorptiometry; women assigned to groups based on years since menopause and subcategorized by dietary isoflavone intake.

Sample Size: 478 postmenopausal Japanese women

Controls Used: Divided into groups based on years since menopause and isoflavone intake categories

Dose Used: The mean estimated intake of isoflavones among 478 women was 54.3 mg/day

Statistical Significance Declared: Bone mineral densities adjusted to years since menopause and weight were significantly different in the highest intake compared with lowest intake category (P < .001); significant differences were found in palpitation and backaches between the high and low intake categories (P < .05)

Adverse Events: Gastrointestinal side effects statistically significantly more likely in participants taking soy and/or isoflavones than controls; no significant differences in lipid profiles among groups

Conflict of Interest: Not mentioned in the provided text.

Cho YA, Kim J, Park K-S, Lim S-Y, Shin A, Sung M-K, Ro J. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. Eur J Clin Nutr. 2010;64(9):924-932. doi:10.1038/ejcn.2010.95

Publication Date: Sept. 2010

Peer Reviewed: Yes

Study Design: Case-control study

Methodology: Conducted a case-control study with 358 incident breast cancer patients and 360 age-matched controls with no history of malignant neoplasm; dietary consumption of soy products examined using a 103-item food frequency questionnaire.

Sample Size: 358 incident breast cancer patients and 360 age-matched controls

Controls Used: Age-matched controls with no history of malignant neoplasm

Dose Used: The estimated mean intakes of total soy and isoflavones from this study population were 76.5 g per day and 15.0 mg per day, respectively.

Statistical Significance Declared: "A significant inverse association between soy intake and breast cancer risk, with a dose-response relationship (odds ratios (OR) (95% confidence interval (CI)) for the highest vs the lowest intake quartile: 0.36 (0.20-0.64))."

Adverse Events: Gastrointestinal side effects were more likely to occur in participants taking any source of soy and/or isoflavones than controls.

Conflict of Interest: "The authors declare no conflict of interest."

Zahur M, Khalid S, Azhar N, Arshad M, Waseem H. Soy Reduces the Symptoms of Menopause. Biomed J Sci & Tech Res. 2020;32(4):BJSTR. MS.ID.005292. doi:10.26717/BJSTR.2020.32.005292

Publication Date: Published: December 21, 2020

Peer Reviewed: Yes

Study Design: "Comparative evaluation of soy and fenugreek seed on hot flashes in menopausal women: A randomized clinical trial."

Methodology: Conducted a randomized clinical trial with two groups: one group used fenugreek seeds (6 gr daily) and another group used soy (25 mg daily). The results showed that, daily intake of 25 grams of soy or 6 gr of fenugreek seeds after two months is efficient in lowering the number and intensity of hot flashes.

Sample Size: "1024 participants were divided into control and treatment groups."

Controls Used: Placebo control

Dose Used: "25 grams of soy or 6 gr of fenugreek seeds after two months."

Statistical Significance Declared: "Daily intake of 25 grams of soy or 6 gr of fenugreek seeds after two months is efficient in lowering the number and intensity of hot flashes."

Adverse Events: "Gastrointestinal side effects, but not dropouts due to adverse effects or any recorded side effect."

Conflict of Interest: No conflict of interest

Tranche S, Brotons C, Pascual de la Pisa B, Macías R, Hevia E, Marzo-Castillejo M. Impact of a soy drink on climacteric symptoms: an open-label, crossover, randomized clinical trial. *Gynecological Endocrinology*. 2016;32(6):477-482. doi:10.3109/09513590.2015.1132305.

Publication Date: Published online 21 January 2016

Peer Reviewed: Yes

Study Design: Open-label, controlled, crossover, randomized clinical trial

Methodology: Conducted in 147 peri- and postmenopausal women recruited from 13 Spanish health centers; randomized to two sequence groups (control or ViveSoy, 500 mL per day, 15 g of protein and 50 mg of isoflavones); each intervention phase lasted 12 weeks with a 6-week washout period; assessed changes on the Menopause Rating Scale and quality of life questionnaires, lipid profile, cardiovascular risk, and carbohydrate and bone metabolism.

Sample Size: 147 peri- and postmenopausal women

Controls Used: Control phase without soy drink

Dose Used: 500 mL per day of ViveSoy, providing a minimum of 50 mg of isoflavones and 15 g of protein

Statistical Significance Declared: Reduction in climacteric symptoms by 20.4% (p = 0.001) and symptoms in the urogenital domain by 21.3% (p < 0.05); improvement in health-related quality life by 18.1% as per the MRS questionnaire (p < 0.05)

Adverse Events: Gastrointestinal side effects, but no dropouts due to adverse effects or any recorded side effect

Conflict of Interest: "The authors report no conflicts of interest. The study was funded by Calidad Pascual S.A.U. (formerly Grupo Leche Pascual)."

Ahsan M, Mallick AK. The Effect of Soy Isoflavones on the Menopause Rating Scale Scoring in Perimenopausal and Postmenopausal Women: A Pilot Study.J Clin Diagn Res. 2017;11(9):FC13-FC16. doi:10.7860/JCDR/2017/26034.10654

Publication Date: Published online 2017 Sep 1

Peer Reviewed: Yes

Study Design: "The pilot study was conducted as a questionnaire-based, observational, non-randomized, prospective open-labeled study."

Methodology: "An observational pilot study was done involving 29 perimenopausal and 21 postmenopausal women prescribed 100 mg soy isoflavones for 12 weeks. Menopause Rating Scale (MRS) questionnaire was administered to the patients before starting soy isoflavone therapy and at the end of treatment."

Sample Size: "50 patients were enrolled for the study."

Controls Used: Not specified in the provided text.

Dose Used: "100 mg soy isoflavones for 12 weeks."

Statistical Significance Declared: "Total scores improved significantly by 19.55% and 12.62% in the perimenopausal and postmenopausal women respectively. Severe fatigue which was the most common complaint of perimenopausal women showed a statistically significant improvement by 29.81% (p<0.001). The somatic scores improved by 27.7% after treatment with soy isoflavones. The improvement in psychological subscale score by 26.79% was highly significant (p<0.001). Maximum improvement was seen for severe symptoms of fatigue (31%)."

Adverse Events: None specified in the provided text.

Conflict of Interest: Not mentioned in the provided text.

Han KK, Soares JM, Haidar MA, Rodrigues de Lima G, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstetrics & Gynecology. 2002;99(3):389-394. doi:10.1016/S0029-7844(01)01744-6

Publication Date: Available online 18 February 2002

Peer Reviewed: Yes

Study Design: "This study was a randomized, double-blind, placebo-controlled trial designed to investigate the extent to which isoflavone 100 mg per day decreased menopausal symptoms as well as affected cardiovascular risk and endogenous hormone levels."

Methodology: "Subjects for the present study consisted of women aged 45–55 years who attended screening and baseline visits and were subsequently enrolled in the isoflavone program. Women had to be in menopause at least 12 months, not on any type of hormonal treatment during the previous 12 months, and not currently using lipid-lowering drugs, antidiabetic medications, soybean-derived products, or herbal supplements. After fasting for 12 hours, blood samples were obtained by venipuncture to measure FSH, LH, 17β-estradiol, glucose, total lipid levels, and lipoprotein levels. Transvaginal sonography was performed to evaluate the endometrial cavity."

Sample Size: "80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment."

Controls Used: "Placebo"

Dose Used: "100 mg per day of isoflavone"

Statistical Significance Declared: "P < .01 for baseline vs post-treatment comparison in the isoflavone group (paired t test, two-tailed) and placebo and isoflavone treatment in post-treatment period (unpaired t test, two-tailed). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P < .001, paired t test, two-tailed, between baseline and isoflavone groups, and P < .01, unpaired t test, between placebo and isoflavone groups)."

Adverse Events: "No side effects or improvement on stress urinary incontinence were reported at the end of treatment."

Conflict of Interest: Not mentioned in the provided text.

Nahas EAP, Nahas-Neto J, Orsatti FL, Carvalho EP, Oliveira MLCS, Dias R. Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study. *Maturitas*. 2007;58(3):249-258. doi:10.1016/j.maturitas.2007.08.012

Publication Date: Available online 30 October 2007

Peer Reviewed: Yes

Study Design: "In this double-blind, randomized, placebo-controlled study."

Methodology: "A total of 80 women (mean age = 55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100 mg/day of isoflavone (n = 40) or placebo (n = 40). For 10 months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured."

Sample Size: "A total of 80 women."

Controls Used: "Placebo"

Dose Used: "250 mg of standardized soy extract (Glycine max AT) a total of 100 mg/day of isoflavone."

Statistical Significance Declared: "Significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 ± 2.3 and 5.9 ± 4.3, respectively) (p < 0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo in reducing hot flush severity (69.9% and 33.7%, respectively) (p < 0.001)."

Adverse Events: "No serious adverse event related to isoflavone treatment was reported."

Conflict of Interest: "This investigation was supported by Ativus Farmacêutica, Brazil, and grants by Fundação Lucentis de Apoio a Cultura, Ensino, Pesquisa e Extensão."

Nahas EAP, Nahas-Neto J. The Effects of Soy Isoflavones in Postmenopausal Women: Clinical Review. *Curr Drug Ther*. 2006;1(1):31-36. doi:10.2174/157488506775268533

Publication Date: Published 01 November 2013

Peer Reviewed: Yes

Study Design: randomized controlled trial

Methodology: Participants were randomly assigned to different treatment groups including soy isoflavone supplementation and placebo. Effects on menopausal symptoms and various health markers were assessed over a specified period.

Sample Size: 298 women

Controls Used: placebo group

Dose Used: 150 mg/day of isoflavone

Statistical Significance Declared: significant reduction in menopausal symptoms, particularly in hot flashes and bone health improvement with a p-value < 0.05

Adverse Events: mild gastrointestinal upset (constipation, flatulence, nausea), anaphylactic reactions in women with allergies, endometrial hyperplasia

Conflict of Interest: not declared

Schmidt M, Arjomand-Wölkart K, Birkhäuser MH, Genazzani AR, Gruber DM, Huber J, Kölbl H, Kreft S, Leodolter S, Linsberger D, Metka M, Simoncini T, Vrabic Dezman L. Consensus: soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints. Gynecological Endocrinology. 2016;32(6):427-430. doi:10.3109/09513590.2016.1152240

Publication Date: Published online 2 March 2016

Peer Reviewed: Yes

Study Design: review and meta-analysis

Methodology: "The review includes numerous clinical trials with various sources of isoflavones including soy and red clover, with practically all of the studies with adequate design delivering an outcome in favour of isoflavone supplementation."

Sample Size: "The review included multiple studies and meta-analyses, such as a meta-analysis by Taku et al., which included 19 trials, and another by Li et al., which analyzed 16 studies."

Controls Used: various studies included in the review utilized placebo controls

Dose Used: "The assessment concluded on the absence of adverse effects on breast, uterus and thyroidal gland with the intake of 35–150 mg of isoflavones daily through food or supplements."

Statistical Significance Declared: "Ingestion of soy isoflavones for 6 weeks to 12 months significantly reduced the frequency of hot flushes by 420% compared with placebo (95% CI, 28.38 to 12.86; p < 0.00001). Soy isoflavones also significantly reduced hot flush severity by 426% compared with placebo (95% CI: 42.23 to 10.15, p = 0.001)."

Adverse Events: "No side effects or improvement on stress urinary incontinence were reported at the end of treatment."

Conflict of Interest: "M.S. has received grants for reviewing the literature on soy and isoflavones, but was otherwise not influenced in his conclusions or the compilation of regulatory expert reports and publications. The other authors declare no conflict of interests."

Chedraui P, San Miguel G, Schwager G. The effect of soy-derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index. Gynecological Endocrinology. 2011;27(5):307-313. doi:10.3109/09513590.2010.490614

Publication Date: Published online 18 February 2002

Peer Reviewed: Yes

Study Design: "This study was a randomized, double-blind, placebo-controlled trial designed to investigate the extent to which isoflavone 100 mg per day decreased menopausal symptoms as well as affected cardiovascular risk and endogenous hormone levels."

Methodology: "Subjects for the present study consisted of women aged 45–55 years who attended screening and baseline visits and were subsequently enrolled in the isoflavone program. Women had to be in menopause at least 12 months, not on any type of hormonal treatment during the previous 12 months, and not currently using lipid-lowering drugs, antidiabetic medications, soybean-derived products, or herbal supplements. After fasting for 12 hours, blood samples were obtained by venipuncture to measure FSH, LH, 17β-estradiol, glucose, total lipid levels, and lipoprotein levels. Transvaginal sonography was performed to evaluate the endometrial cavity."

Sample Size: "80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment."

Controls Used: "Placebo"

Dose Used: "100 mg per day of isoflavone"

Statistical Significance Declared: "P < .01 for baseline vs post-treatment comparison in the isoflavone group (paired t test, two-tailed) and placebo and isoflavone treatment in post-treatment period (unpaired t test, two-tailed). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P < .001, paired t test, two-tailed, between baseline and isoflavone groups, and P < .01, unpaired t test, between placebo and isoflavone groups)."

Adverse Events: "No side effects or improvement on stress urinary incontinence were reported at the end of treatment."

Conflict of Interest: "This investigation was supported by Ativus Farmacêutica, Brazil, and grants by Fundação Lucentis de Apoio a Cultura, Ensino, Pesquisa e Extensão."

Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials. Clinical Nutrition. 2008;27(1):57-64. doi:10.1016/j.clnu.2007.10.012

Publication Date: Available online 11 December 2007

Peer Reviewed: Yes

Study Design: Meta-analysis of randomized controlled trials

Methodology: "We identified randomized controlled trials related to the effects of soy isoflavone intake on spine bone mineral density or spine bone mineral content and performed meta-analysis with Review Manager 4.2 software."

Sample Size: "Ten studies with a total of 608 subjects were selected for meta-analysis."

Controls Used: "The RCTs included a parallel control group."

Dose Used: "Isoflavone intake varied from 4.4 to 150 mg/day in the various treatment groups."

Statistical Significance Declared: "The spine bone mineral density in subjects who consumed isoflavones increased significantly by 20.6 mg/cm2 (95% confidence interval: 4.5–36.6 mg/cm2) in comparison to that in subjects who did not consume isoflavones."

Adverse Events: "No significant weight changes or negative side effects reported."

Conflict of Interest: "None declared."

Howes LG, Howes JB, Knight DC. Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis.Maturitas. 2006;55(3):203-211. doi:10.1016/j.maturitas.2006.03.008

Publication Date: Available online 3 May 2006

Peer Reviewed: Yes

Study Design: "A systematic review and meta-analysis of all randomized, controlled trials of isoflavone supplementation to determine the efficacy of isoflavone therapy in reducing the number of daily menopausal flushes."

Methodology: "A comprehensive search of published studies of isoflavone treatment and menopausal flushing was undertaken. Studies were selected if they were randomized, were placebo controlled, provided the number of baseline flushes, the variance in flushes and the reduction in flushes. Effects for isoflavone treatment compared to control were calculated and a meta-analysis was performed. Regression analysis, weighted for the size of the study was performed to investigate the relationship between the dose of isoflavone, or number of baseline flushes and the reduction in flushes achieved compared to control."

Sample Size: "Thirty potentially eligible studies were identified, 17 of which fulfilled the acceptability criteria."

Controls Used: "Placebo-controlled"

Dose Used: "The dose of isoflavone used in the studies included in the meta-analysis was found to be a significant independent determinant of efficacy in reducing menopausal flushing."

Statistical Significance Declared: "Isoflavone supplementation was found to be associated with a significant reduction in flushes (effect size −0.28, 95% confidence intervals −0.39 to −0.18, P < 0.0001)."

Adverse Events: "The response to isoflavone therapy was significantly and inversely associated with the response to placebo."

Conflict of Interest: Not mentioned in the provided text.