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Logo of bmjThis ArticleThe BMJ
BMJ. 2007 August 11; 335(7614): 299.
PMCID: PMC1941896

Soy phytoestrogen genistein increases bone mineral density in postmenopausal women


Research question Can genistein reduce bone loss in osteopenic postmenopausal women?

Answer Yes, but it's still unclear whether genistein helps prevent fractures.

Why did the authors do the study? Small, brief trials suggest that the phytoestrogen genistein, found in many soy products, can help prevent bone loss after the menopause. These authors wanted to extend and confirm these preliminary findings.

What did they do? 389 Italian women took part in a double blind, randomised, controlled trial. All were postmenopausal and had osteopenia (with a bone mineral density at the femoral neck of <0.795 g/cm2) but were otherwise well. After randomisation, 198 women took a pill containing 54 mg genistein daily for two years. The rest took a matching placebo. Both pills contained calcium and vitamin D. All the women ate a low fat diet designed to meet their daily energy requirements.

The authors were particularly interested in the effects of genistein on bone mineral density at the femoral neck and lumbar spine, which they measured at baseline and then after one and two years. They also looked for changes in urinary markers of bone resorption and serum markers of bone formation and growth. They asked women about menopausal symptoms and side effects every three months, and measured endometrial thickness before and after treatment to asses the effects of genistein on the uterus. Their study was powerful enough to detect a difference in bone mineral density of at least 20% between the two groups after two years. The authors used intention to treat analysis to compare groups.

What did they find? Bone mineral density increased among the women taking genistein and decreased among those taking placebo, leading to a difference at two years of 0.10 g/cm2 (95% CI 0.08 to 0.12, P<0.001) at the lumbar spine and 0.062 g/cm2 (0.049 to 0.073, P<0.001) at the femoral neck. Compared with placebo, genistein increased serum concentrations of bone specific alkaline phosphatase and insulin-like growth factor 1 (both serum markers of bone formation) and decreased urinary excretion of pyridinoline and deoxypyridinoline (markers of bone resorption). It had no measurable effect on endometrial thickness.

Women taking genistein reported significantly fewer hot flushes than controls (mean 1.7 per day v 3.9 per day, P<0.001), but they had more gastrointestinal side effects and were more likely to drop out of the study early (19% v 8%). Constipation (13/198, 7%) and dyspepsia (9/198, 5%) were the commonest side effects associated with genistein.

What does it mean? Genistein, an isoflavone phytoestrogen, seems to have positive effects on bone mineral density and bone turnover in osteopenic women who are at least one year past the menopause. But about one in five women in this trial stopped their treatment early, so gastrointestinal side effects may be a problem.

Although these data look encouraging, the authors looked only at surrogate measures of effectiveness and safety. Bigger trials are now required with the power to find out if genistein can reduce the risk of osteoporotic fractures without increasing women's risk of uterine cancer.


  • Marini et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med 2007;146:839-47 [PubMed]

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