Taking soy supplements won't ease the symptoms of menopause or protect against bone loss in women, researchers have found.
Over two years, there were no differences in changes in bone density or menopausal symptoms between women taking soy and those taking a placebo, although women taking isoflavones did have more hot flashes, Silvina Levis, MD, of the University of Miami, and colleagues reported in the August 8/22 issue of Archives of Internal Medicine.
Since results of the Women's Health Initiative tied hormone replacement therapy to several adverse effects, particularly cardiovascular disease, women have been searching for alternative treatments for menopausal symptoms.
Many have turned to soy, which contains phytoestrogens, specifically the isolflavones genistein and daidzein, the researchers wrote. Studies have shown a lower prevalence of osteoporotic fractures, breast cancer, and cardiovascular disease in Asian women, which has been largely attributed to their soy-rich diets.
Yet prior evidence for the efficacy of soy supplementation has been limited by poor study design, small sample size, and short duration of treatment.
So to clarify previous findings, the researchers conducted the Soy Phytoestrogens As Replacement Estrogen (SPARE) study, a single-center randomized, controlled, double-blind trial, in 248 women, ages 45 to 60, between July 1, 2004 and March 31, 2009.
All of the women were within five years of the start of menopause, and had a bone mineral density score of -2.0 or higher at the lumbar spine or total hip.
They were randomized to placebo, or to 200 mg daily of soy isoflavone tablets (91 mg genistein, 103 mg daidzein).
The primary outcome was change in bone density at the lumbar spine, total hip, and femoral neck after two years, and secondary outcomes included changes in menopausal symptoms.
After two years, the researchers found no significant differences in any measurements of bone mineral density between those on soy versus those on placebo:
- -2% versus -2.3% at the lumbar spine
- -1.2% versus -1.4% at the total hip
- -2.2% versus -2.1% at the femoral neck
Levis and colleagues found no differences when controlling for confounders, except with regard to vitamin D status. Women whose levels were below 20 ng/mL in the placebo group had a significantly greater decrease in spinal bone density than those taking soy (P=0.03).
With regard to secondary outcomes, the researchers found that significantly more women taking soy supplements had hot flashes (48.4% versus 31.7%, P=0.02).
There no differences in vaginal cytologic characteristics or cholesterol, triglycerides, or thyrotropin levels between groups, they reported.
As well, there were no differences between the groups in adverse effects, except those on soy reported more constipation, a finding of marginal significance (31.2% versus 20.6%, P=0.06).
Overall, there were 12 serious adverse events -- nine in the soy group and three in the placebo group. Seven women in the soy group reported fractures compared with just one on placebo (P=0.03). All these fractures were associated with a traumatic event and not considered to be osteoporotic fractures, the researchers noted.
There was also a higher dropout rate in the placebo group (34.1% versus 18.8%), but Levis and colleagues said the numbers don't necessarily indicate favorable effects for soy because there was no objective documentation of a benefit. In a post hoc survey, similar proportions of patients in both arms thought they were in the active group.
The dropout rate was one limitation of the study, because it was higher than expected, the researchers said. Also, the small amount of bone loss overall may have precluded detection of any treatment effects.
They noted, however, that their population was largely white and overweight, two groups known to have some protection against bone loss.
In an invited commentary, Katherine Newton, PhD, of Group Health in Seattle, and Deborah Grady, MD, MPH, of the University of California San Francisco, wrote that questions still remain as to whether soy may have benefits in specific groups.
For instance, they wrote, a metabolic product of daidzein known as equol is thought to be more biologically active than daidzein, but only 25% to 50% of women metabolize daidzein into equol.
Though the study found no enhanced effects for equol producers, Newton and Grady said this metabolite should have been measured immediately after daidzein ingestion in order to accurately assess equol producer status. Thus, these findings may require further investigation, they wrote.
In general, they said, efforts may need to move "away from the hope of a one-size-fits-all therapy for menopausal symptoms towards using existing treatments to target the symptoms that disturb patients most," adding that non-hormonal therapies, such as selective serotonin reuptake inhibitors and gabapentin, may be effective treatments.
This article was developed in collaboration with ABC News.
Primary source: Archives of Internal Medicine Source reference: Levis S, et al "Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms" Arch Intern Med 2011; 171(15): 1363-1369.
Additional source: Archives of Internal Medicine Source reference: Newton KM, Grady D "Soy isoflavones for prevention of menopausal bone loss and vasomotor symptoms" Arch Intern Med 2011; 171(15): 1369-1370.
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
August 8, 2011
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