Soy

Soy

PEP Topic 
Hot Flashes
Description 

Soy, a plant in the pea family, has been common in Asian diets for thousands of years. It is found in modern American diets as a food or food additive. Soybeans, the high-protein seeds of the soy plant, contain isoflavones—compounds similar to the female hormone estrogen. Some studies suggest that soy isoflavone supplements may reduce hot flashes in women after menopause. The safety of long-term use of soy isoflavones has not been established. Soy has been studied as an intervention for hot flashes in patients with cancer.

Effectiveness Unlikely

Research Evidence Summaries

MacGregor, C.A., Canney, P.A., Patterson, G., McDonald, R., & Paul, J. (2005). A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. European Journal of Cancer, 41, 708–714.

doi:10.1016/j.ejca.2005.01.005
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Study Purpose:

The study looked at soy supplements versus placebo for treatment of menopausal symptoms in participants with early breast cancer and hot flashes.

Intervention Characteristics/Basic Study Process:

Participants were randomized to receive either two soy capsules or two identical placebo capsules twice daily for 12 weeks in a double-blind fashion. The soy capsules each contained 235 mg of soy extract with 17.5 mg of isoflavones. Total dose of isoflavones was 70 mg/day. 

Sample Characteristics:

Seventy-two (72) participants with early breast cancer and hot flashes were randomized to 12 weeks of treatment with soy capsules or with placebo. To be considered a worthwhile treatment strategy, soy extract would need to benefit around half of the participants treated. Thus, 32 evaluable participants per arm were needed.  The median age was 51 years. Any concomitant medications for preexisting disease were allowed.

Study Design:

The randomized double-blind controlled trial was stratified for initial sweating/flushing score (< 2, p = 2); age at randomization (younger than 50 years, older than 50 years); currently having adjuvant tamoxifen or after ovarian suppression (yes or no).

Measurement Instruments/Methods:

QOL and menopausal symptoms scores were assessed at baseline and weeks 4, 8, and 12. A four-question menopausal scale was developed for the study to assess control of menopausal symptoms measured by combined estimates of severity of sweats (day or night) and flushes.

Results:

There was no significant difference in menopausal symptoms between the placebo and soy capsule arms of the study.Toxicity was mild and primarily gastrointestinal. There was no significant difference in toxicity between the 2 arms.

Nikander, E., Metsa-Heikkila, M., Ylikorkala, O., & Tiitinen, A. (2004). Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of Clinical Endocrinology and Metabolism, 89, 1207–1212.

doi:10.1016/j.ejca.2005.01.005
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Study Purpose:

The study explored the effects of daily use of isoflavonoids on climacteric symptoms and QOL in postmenopausal women who had been treated for breast cancer.

Intervention Characteristics/Basic Study Process:

Phytoestrogen tablets and similar-looking placebo tablets (six tablets per day) were taken every 12 hours with a glass of water. The participants were seen at the research center before and after each treatment period. Sixty-two postmenopausal, symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for three months; the treatment regimens were reversed after a 2-month washout period.

Sample Characteristics:

Six women discontinued the trial for various reasons during the first phase. Thus, 56 women completed the study. The mean age pf participants was 54 (± 6 years).

  • Inclusion criteria: breast cancer survivors (none using tamoxifen) who reported incapacitating hot flashes and other climacteric symptoms after the onset of spontaneous menopause, as seen from their high circulating levels of FSH and LH. 
  • Exclusion criteria: Use of sex steroids (including tamoxifen); use of natural products with possible estrogenic activity; use of drugs possibly affecting climacteric symptoms, metabolism, or absorption of phytoestrogens (e.g., antibiotics during the previous three months); and history of any thromboembolic or hepatic event.

Study Design:

This was a randomized placebo-controlled crossover trial of phytoestrogens in treatment of menopause in breast cancer participants.

Measurement Instruments/Methods:

At each visit, the participants were interviewed about hot flashes and other typical climacteric symptoms using the Kupperman index and Menopausal Visual Analogue scale. Blood levels of phytoestrogens, FSH, LH, estradiol, and sex hormone-binding globulin, liver enzymes, and creatinine levels were followed. Compliance with treatment was confirmed by diary records and by measurement of serum phytoestrogen levels.

Results:

The use of phytoestrogens led to significant rises in the levels of phytoestrogens, whereas the placebo regimen had no effect. Kupperman indexes at the end of treatment with phytoestrogen or placebo did not differ. Hot flashes and the other components of the Kupperman index were not relieved by the phytoestrogen regimen when evaluated separately.

Conclusions:

Pure isoflavonoids at a dose of 114 mg for three months did not relieve hot flashes or other menopausal symptoms in participants with breast cancer

Limitations:

Potential limitations of the trial included:

  1. Study period was of short duration (three months). 
  2. Possibility that phytoestrogens may trigger changes in target organs in processes requiring more than three months. It would be valuable to have long-term data on the effects of phytoestrogens.
  3. Were doses physiologically suitable? Doses appeared sufficiently large, given the elevations in phytoestrogen levels in participants.

Quella, S.K., Loprinzi, C.L., Barton, D.L., Knost, J.A., Sloan, J.A., LaVasseur, B.I., … Novotny, P.J. (2000). Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group trial. Journal of Clinical Oncology, 18, 1068–1074. 

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Study Purpose:

The study evaluated soy phytoestrogens for the treatment of hot flashes in breast cancer survivors.

Intervention Characteristics/Basic Study Process:

After a baseline documentation week, women received four weeks of either soy tablets or placebo. They then crossed-over to the opposite for the last four weeks. The soy product was formulated in 600 mg tablets. Participants took one tablet three times per day (150 mg of isoflavones day), an amount similar to that consumed with three glasses of soy milk.

Sample Characteristics:

Participants included 177 women with a history of breast cancer; 149 participants (84%) provided useable efficacy data for the entire nine weeks of the study.

Study Design:

All participants were randomized in a double-blind crossover design to one of two groups (soy or placebo) and crossed-over after four weeks. Participants were stratified according to age, duration of hot flashes, and the average daily hot flash frequency using a dynamic allocation procedure that balances marginal distributions. They were also stratified by current tamoxifen or raloxifene use (yes or no).

Measurement Instruments/Methods:

The instrument was a daily questionnaire documenting hot flashes frequency, intensity, and perceived side effects.

Results:

The soy product did not alleviate hot flashes in breast cancer survivors. No toxicity was observed. These data failed to suggest any patient preference for the soy compound over the placebo preparation.

Limitations:

Optimal daily dose of soy required to recognize a clinical response may be questioned. Data related to estimated intake of 150–200 mg daily in the Asian diet endorsed the choice of 150 mg/day. Experience from conventional HRT suggests that length of time on the soy isoflavones (four weeks) may be too short to elicit a clinical response. Study durations of less than three months have been excluded from overviews of the effects of HRT.

Sharma, P., Wisniewski, A., Braga-Basaria, M., Xu, X., Yep, M., Denmeade, S., … Basaria, S. (2009). Lack of an effect of high dose isoflavones in men with prostate cancer undergoing androgen deprivation therapy. Journal of Urology, 182, 2265–2272.

doi:10.1016/j.juro.2009.07.030
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Study Purpose:

The study evaluated the effects of high dose isoflavones, equivalent to that consumed by Asian populations, on the consequences of androgen deprivation therapy (ADT) for prostate cancer, such as sexual dysfunction, poor QOL, vasomotor symptoms, and altered cognition.

Intervention Characteristics/Basic Study Process:

The intervention contained 20 gm Revival® (Physicians Laboratories) soy protein consisting of 160 mg total isoflavones as powder to be mixed with beverages. Placebo contained 20 gm whole milk protein and similar nutrients as the intervention except for isoflavones. Active and placebo powders appeared and tasted similar. Supplements were ingested once daily for 12 weeks, and dispensed at the baseline and 6-week visits. Data were gathered at study baseline, and weeks 6 and 12. Men tolerated the compound well with only one withdrawing from study because he disliked its taste. Overall compliance was high at approximately 80%. Compliance was based on the number of sachets returned by each patient at treatment weeks 6 and 12. 

Sample Characteristics:

This was a 12-week pilot trial of high-dose isoflavones ingested by 39 men with prostate cancer undergoing ADT. Participants were randomly assigned to receive 20 gm soy protein containing 160 mg total isoflavones (17) versus taste-matched placebo (20 gm whole milk protein).  After enrollment, men were instructed to refrain from ingesting any kind of soy product during the 12-week study period. Thirty-three (33) completed the study.

  • Inclusion criteria: Men 21 years old or older undergoing medical or surgical ADT for at least three months.
  • Exclusion criteria: Hepatic, renal, thyroid or neurologic disease, active psychiatric disorder, current chemotherapy or glucocorticoids, appetite or weight promoting agents, substance abuse, triglycerides greater than 500 mg/dl, or allergy to soy protein or cow milk.

Men already on soy supplements were washed out for at least three months before entry.

Study Design:

Study was a randomized, double-blind, placebo-controlled trial.

Results:

Men were not well matched for hot flashes, with the isoflavones group reporting higher scores (increased distress) than men on placebo at baseline and at study end. However, within-group analysis showed no significant changes in the vasomotor distress score in either group. Using the Kupperman scale, men on isoflavones did not show any significant improvement in hot flashes compared to those on placebo. At 12 weeks, there were no significant differences between the two groups in any outcome measure. No safety issues were found during the study.

Conclusions:

This pilot study of high-dose isoflavones in androgen deprived men showed no significant improvement in cognition, vasomotor symptoms, or any other aspect of QOL measures compared to placebo.

Limitations:

This pilot study had a small sample size and short treatment duration. Future studies should use variable doses of isoflavones for a longer period before ruling out beneficial isoflavone effects in this population.

Van Patten, C.L. (2002). Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: A randomized, controlled clinical trial. Journal of Clinical Oncology, 20, 1449–1455.

doi:10.1200/JCO.20.6.1449
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Study Purpose:

The study examined the effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer:

Sample Characteristics:

The study randomized 157 participants with a mean age of 55 years and who had been previously treated for breast cancer from August 1998 to February 2000. Nine women (6%) became ineligible after randomization, and 25 (16%) dropped out because of time commitment (n = 9), intolerance of the study beverage (n = 10, 7 in the soy group, 3 in the placebo group), or other reasons (n = 6). The remaining 123 women completed the study by June 2000.

  •  Inclusion criteria:
    • Women had completed treatment for breast cancer more than four months prior to enrollment (tamoxifen use was allowed), were menopausal (12 or more months of amenorrhea), and had not used HRT for 4 or more months, were experiencing troubling hot flashes, defined as a score (frequency × intensity) of 10 or more per week.
    • Women using complementary therapies and prescription medications, including tamoxifen, were eligible if no change in therapy for four months or longer.
    • All participants were instructed to avoid soy-based foods and soy supplements during the study.
  • Exclusion criteria:
    • Based primarily on factors that modify estrogen or phytoestrogen metabolism or that had the potential to require medical intervention: smokers, using antibiotics, inflammatory bowel disease, liver impairment (gamma-glutamyl transferase and alkaline phosphatase of ≥ 1.5 times normal), or recurrent breast cancer.
    • Also, soy allergy or regular consumption of soy foods.

Study Design:

In this randomized, placebo-controlled, double-blind clinical trial, participants were stratified for tamoxifen use and randomized to a soy beverage (n = 59) containing 90 mg of isoflavones or to a placebo rice beverage (n= 64).

Measurement Instruments/Methods:

Women recorded the number/severity of hot flashes with a daily diary for 4 weeks at baseline, then for 12 weeks while consuming 500 ml of a soy or placebo beverage daily. The primary outcome variable was the mean 24-hour hot flash score, created by summing the hot flash score (frequency × intensity) during the day and night. The main analysis, with Student’s t test, was a comparison between groups in the change in the mean 24-hour hot flash score during the 4 weeks of baseline compared with the last 4 weeks of treatment. This analysis was also conducted for the hot flash number and score during the day and night and the hot flash number per 24 hours. Secondary analyses included a comparison between groups of:

  1. Consumption and acceptability ratings for each beverage
  2. Frequency of side effects
  3. Responses to the study exit questionnaire
  4. Serum isoflavone concentrations

The average serum isoflavone concentration of the soy beverage was also calculated. All statistical tests were two-tailed and used a significance level of alpha = 0.05.

Conclusions:

This trial does not support the use of a soy beverage containing phytoestrogens as a treatment for hot flashes in breast cancer survivors. The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo. Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy.

Vitolins, M.Z., Griffin, L., Tomlinson, W.V., Vuky, J., Adams, P.T., Moose, D., . . . Shaw, E.G. (2013). Randomized trial to assess the impact of venlafaxine and soy protein on hot flashes and quality of life in men with prostate cancer. Journal of Clinical Oncology, 31, 4092–4098.  

doi: 10.1200/JCO.2012.48.1432
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Study Purpose:

To determine the effectiveness of venlafaxine, soy, and a combination of venlafaxine and soy on hot flashes in men with prostate cancer

Intervention Characteristics/Basic Study Process:

Participants randomly were assigned to one of four groups: daily placebo pill in the morning plus daily milk powder (20 g per day); daily venlafaxine (75 mg) in the morning plus daily milk powder (20 g per day); daily placebo pill in the morning plus daily soy powder (20 g with 160 mg isoflavones); or daily venlafaxine (75 mg) in the morning plus daily soy powder (20 g with 160 mg isoflavones). Venlafaxine was provided in extended-release capsules. Prior to enrollment, participants completed a seven-day prescreening period. The intervention was administered for 12 weeks. Patients kept a daily log of medications and were contacted via phone at week 2, 4, 8, and 12 to assess toxicities and complete study measures. Patients on venlafaxine were titrated off medication after the end of the study.

Sample Characteristics:

  • N = 119
  • MEAN AGE = 68.5 years
  • AGE RANGE = 46–91 years
  • MALES: 100%
  • KEY DISEASE CHARACTERISTICS: Prostate cancer

Setting:

  • SITE: Single site    
  • SETTING TYPE: Outpatient    
  • LOCATION: United States

Phase of Care and Clinical Applications:

PHASE OF CARE: Late effects and survivorship

Study Design:

  • RCT, double-blind, placebo-controlled, 2 x 2 factorial design

Measurement Instruments/Methods:

  • Daily count of hot flashes
  • Hot Flash Symptom Severity Score (HFSSS)
  • Functional Assessment of Cancer Therapy-Prostate (FACT-P)
  • Body mass index (BMI)

Results:

There was no significant difference in sample characteristics between the four groups including severity of disease, BMI, performance status, and type of treatment. Vasomotor symptoms decreased in all arms (p < 0.001). No differences existed between treatment arms at baseline and 4, 8, or 12 weeks. The severity of hot flashes decreased in all arms (p < 0.001). All four arms showed a decrease in the HFSSS (p < 0.001). Toxicities did not differ between groups and were mild. The study was ended by the Data Safety Monitoring Board due to a lack of effect. The placebo group had the largest decrease in HFSSS scores (55%).

Conclusions:

In men with prostate cancer, venlafaxine, soy, and a combination of the two were no more effective than a placebo at decreasing the number and severity of hot flashes.

Nursing Implications:

Venlafaxine, soy, and a combination of both are not effective at treating hot flashes in men with prostate cancer.


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