Background:No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women. Objective: Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the menopausal transition. Design: Perimenopausal subjects were randomly assigned, double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor soy (SPIϪ; n = 24), or whey (control; n = 21) protein. At baseline and posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline, midtreatment, and posttreatment, urinary N-telopeptides and serum bonespecific alkaline phosphatase (BAP) were measured. Results: The percentage change in lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or SPIϪ groups, but loss occurred in the control group (Ϫ1.28%, P = 0.0041; Ϫ1.73%, P = 0.0037). By regression analysis, SPI+ treatment had a positive effect on change in BMD (5.6%; P = 0.023) and BMC (10.1%; P = 0.0032). Baseline BMD and BMC (P ≤ 0.0001) negatively affected the percentage change in their respective models; baseline body weight (P = 0.0036) and bone-free lean weight (P = 0.016) contributed positively to percentage change in BMD and BMC, respectively. Serum BAP posttreatment was negatively related to percentage change in BMD (P = 0.0016) and BMC (P = 0.019). Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones, not soy protein, exerted the effect. Conclusion: Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women.Am J Clin Nutr 2000; 72:844-52. KEY WORDSSoy, isoflavones, bone density, lumbar vertebrae, biochemical markers, menopause, bone mineral content, perimenopausal women INTRODUCTIONCurrent therapies for treating osteoporosis include estrogen and hormone replacement therapies (ERT and HRT), bisphosphonates, calcitonin, and raloxifene. Because of possible contraindications of ERT and HRT, such as breast cancer, endometrial adenocarcinoma, and undesirable side effects (1), compliance with hormonal therapy is poor (2), leading to loss of treatment efficacy (3). Continued uterine bleeding and other adverse side effects of HRT cause women to search for alternatives to traditional therapy. Isoflavone-containing soy may be a potential alternative for preventing bone loss during the menopausal transition.Isoflavones, found predominantly in soy products, are estrogen-like substances structurally and functionally similar to 17 ␤-estradiol (4). On the basis of evidence primarily from animal and in vitro studies, isoflavones are thought to exert both estrogenic and antiestrogenic effects, depending on the tissue in which they act (5). Isoflavones may exert a weak antagonistic effect on the estrogen receptor (5), thereby having an antiestrogenic effect on uterine and breast tissue (6), where excess estrogen ...

Our results do not show a bone-sparing effect of extracted soy isoflavones, except for a modest effect at the femoral neck. This trial was registered at clinicaltrials.gov as NCT00043745.

In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.

Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals, thereby reducing cardiovascular disease risk. The primary purpose was to determine the effect of soy protein (40 g/d) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We also determined the contribution of coagulation and fibrinolytic and other factors (e.g., body size and composition; serum estrogens, ferritin, iron; dietary intake) to lipid profiles. Subjects were randomly assigned to treatment: isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n = 21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12 and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24. Coagulation and fibrinolytic factors were not adversely affected by treatment. Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or in all subjects combined. Time significantly (P < 0.001) affected serum total cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations. We could not attribute changes over time to various factors, but at baseline accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for 50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E and % energy from fat had positive effects, whereas plasma plasminogen activator inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids. The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women.