Women who took the supplements every day for two years didn't have any improvement in their symptoms compared with those who took a soy-free placebo pill - and they suffered more hot flashes by the end of a Florida study.
The controlled study involving nearly 250 US women going through "the change" found soy tablets did not abate hot flushes or bone density loss.
Tablets were no better than placebo over the two-year-long investigation, Archives of Internal Medicine reports.
Researchers also didn't see any changes in their bone mineral density compared to women taking placebos. Low bone mineral density puts women at higher risk of osteoporosis and broken bones.
Women seeking relief from menopause symptoms have been without a clear go-to treatment since the Women's Health Initiative (WHI) study of hormone therapy reported heart and cancer risks with estrogen and progestin use.
Previous studies have shown that soy supplements don't have those same added risks. But the studies have also found mixed results on soy's ability to slow bone weakening and ease hot flashes and other menopause symptoms.
"What prompted us to do this study was in the wake of WHI when many of our patients stopped using hormone therapy," said Dr. Silvina Levis, the study's lead author from the Miller School of Medicine, University of Miami.
"Many of them had just gone to a health food store and started on soy supplements," she told Reuters Health. "The study was started to try to answer a simple question: will these soy isoflavone tablets help women with the issues they were concerned with?"
Levis and her team randomly split 248 women who had recently hit menopause into two groups. For two years, half of the women took 200 milligrams of soy isoflavones every day -- about twice the amount that would be in a soy-rich diet. The other half took placebo pills. None of them knew whether they were getting the real or sham treatment.
Most of the participants were Hispanic, and 182 completed the study.
At their two-year visit, women in both groups had lost the same amount of bone density in their spine and hip since starting the study. They also reported a similar number of menopause symptoms, except more women in the soy group said they had hot flashes -- 48 percent of them, compared to 32 percent in the placebo group.
Women taking the daily soy supplements also reported some of the stomach and digestion problems, such as constipation, that have been linked to soy before, Levis said. But there were no serious side effects related to the supplements, the authors report in Archives of Internal Medicine.
The soy tablets can be bought for about 25 to 50 cents per day.
"When we started the study we wanted this to work, because it would provide an easy and healthy way to help women in the initial stages of menopause," Levis said.
However, "we didn't see any protection from bone loss or any relief from menopause symptoms." After this, she added, "maybe women will reconsider" taking soy tablets during menopause.
William Wong, a nutritionist at Baylor College of Medicine in Houston who didn't participate in the new study, agreed. "The scientific evidence is telling them that they might not receive any benefit" from extra soy, he told Reuters Health.
Wong, whose research has also shown a lack of effect of soy during menopause, said that doesn't mean soy couldn't have health benefits over a longer period of time -- such as if girls started getting more of it during puberty.
Medications including certain anti-depressants may provide relief for menopause symptoms in some women, Levis said. For bone health, Wong recommended regular physical activity, combined with calcium and vitamin D supplements.