Laura N. Hanson

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: a 3-y randomized controlled trial in postmenopausal women

BACKGROUND Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss in midlife women. OBJECTIVE We examined the efficacy of isoflavones (extracted from soy protein) on bone mineral density (BMD) in nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D) and lifestyle (physical activity, dietary intake) factors modulating BMD loss. DESIGN Our double-blind, randomized controlled trial (36 mo) included healthy postmenopausal women (aged 45.8-65.0 y) with intent-to-treat (n = 224) and compliant (n = 208) analyses. Treatment groups consisted of a placebo control group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received 500 mg calcium and 600 IU vitamin D(3). Outcomes included lumbar spine, total proximal femur, femoral neck, and whole-body BMD. RESULTS Analysis of variance for intent-to-treat and compliant (> or =80%) models, respectively, showed no treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46), neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and compliant models, respectively, BMD decreases were as follows: spine (-2.08%, -1.99%), femur (-1.43%, -1.38%), neck (-2.56%, -2.51%), and whole body (-1.66%, -1.62%). Regression analysis (compliant model) indicated that age, whole-body fat mass, and bone resorption were common predictors of BMD change. After adjustment for these factors, 120 mg (compared with placebo) was protective (P = 0.024) for neck BMD. We observed no treatment effect on adverse events, endometrial thickness, or bone markers. CONCLUSION 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.

Association of Oxidative Stress, Iron, and Centralized Fat Mass in Healthy Postmenopausal Women

OBJECTIVE Centralized adiposity, insulin resistance, excess iron, and elevated oxidative stress place postmenopausal women at risk for atherosclerotic cardiovascular disease (CVD). The objective of this study was to determine the relationship among excess iron, oxidative stress, and centralized fat mass in healthy postmenopausal women. METHODS The parent project recruited healthy women for a randomized, double-blind, clinical trial designed to examine the effect of soy isoflavones on bone. At baseline (n = 122), we measured three antioxidant enzymes, iron status indices (serum ferritin among others), oxidative stress indices (oxidized low-density lipoprotein [oxLDL], urinary isoprostanes [PGF(2alpha)], protein carbonyls, DNA damage), and waist, hip, and thigh fat mass using dual-energy x-ray absorptiometry (DXA). We calculated insulin resistance using the homeostasis model assessment (HOMA). Multiple regression analysis was used to determine the CVD risk factors that contributed to oxidative stress and centralized fat mass (waist + hip/thigh = AndGynFM ratio). RESULTS Almost 14% (p < 0.0005) of the variability in oxLDL was accounted for by AndGynFM ratio (6.1%, p < 0.0005), age (4.0%, p = 0.012), and serum iron (2.8%, p = 0.053). Similarly, 16% (p < 0.0001) of the variability in PGF(2alpha) was accounted for by the AndGynFM ratio (4.8%, p = 0.011), HOMA (3.9%, p = 0.021), and serum iron (2.7%, p = 0.054). We accounted for 33% (p </= 0.0001) of the variability in AndGynFM ratio by high-density lipoprotein cholesterol (HDL-C) (4.3%, p = 0.008), ferritin (4.9%, p = 0.005), HOMA (4.5%, p = 0.006), oxLDL (2.6%, p = 0.04), and PGF(2alpha) (3.0%, p = 0.025). CONCLUSIONS Our study suggests that reducing centralized fat mass and maintaining a favorable lipid profile, antioxidant status, and iron status all may be important in protecting postmenopausal women from atherosclerotic CVD.

Centrally located body fat is related to inflammatory markers in healthy postmenopausal women

Objective:C-reactive protein and fibrinogen are established atherosclerotic cardiovascular disease risk factors. These acute-phase proteins and the proinflammatory cytokines tumor necrosis factor &agr;, interleukin-6, and interleukin-1&bgr; may be elevated in obesity and with menopause. The purpose of this multicenter study was to identify whether centrally located fat and/or overall adiposity were related to these inflammatory markers in healthy postmenopausal women. Design:We used dual-energy x-ray absorptiometry to assess overall and regional body composition (fat mass in particular) in 242 postmenopausal women in relation to plasma fibrinogen, serum C-reactive protein, and these proinflammatory cytokines. Results:Multiple regression analyses revealed that 36% of the variability in C-reactive protein (F = 32.4, P ≤ 0.0001) was accounted for by androidal fat mass (16.1%, P ≤ 0.0001), white blood cells (5.6%, P ≤ 0.0001), and age (2.3%, P = 0.0045). Regression analyses revealed that 30% of the variability in fibrinogen (F = 24.5, P ≤ 0.0001) was accounted for by white blood cells (3.1%, P = 0.0015), hip fat mass (2.2%, P = 0.0081), years since menopause (0.9%, P = 0.082), and geographic site (P ≤ 0.0001). Our results indicated that androidal fat mass and hip fat mass contributed to C-reactive protein and fibrinogen, respectively, whereas we found no association between whole-body or regional fat measures and cytokines. Conclusion:Further study is warranted to determine the responsiveness of these acute-phase proteins and cytokines to loss of body fat through exercise and dietary intervention in postmenopausal women.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased.

Centrally located body fat is related to appetitive hormones in healthy postmenopausal women

OBJECTIVE Body composition and energy homeostasis are thought to affect the appetitive hormones: adiponectin, leptin, insulin, and ghrelin. This study examined whether centrally located fat and/or overall adiposity were related to these appetitive hormones in healthy postmenopausal women. DESIGN Overall and regional body composition was assessed by dual-energy X ray absorptiometry in relation to plasma adiponectin, serum leptin, serum insulin, and plasma ghrelin in 242 postmenopausal women. RESULTS Regression analyses revealed that the androidal-to-gynoidal fat mass ratio (18.0%), age (3.2%), and white blood cell count (1.8%) accounted for 28% of the variability in adiponectin (F=22.2; P<0.0001); androidal (waist+hip) fat mass (66.0%), androidal fat mass(2) (6.2%), whole-body lean mass (2.2%), and age (0.8%) accounted for 69% of the variability in leptin (F=102.5; P<0.0001). Regression analyses revealed that sagittal abdominal diameter (8.4%), glucose (5.4%), white blood cell count (2.6%), and dietary omega-3 fatty acids (2.0%) accounted for 32% of the variability in insulin (F=20.8; P<0.0001); waist circumference (12.7%), hip lean mass (2.0%), and white blood cell count (1.9%) accounted for 26% of the variability in ghrelin (F=20.7; P<0.0001). Our results indicated that centralized fat mass was the primary contributor to these appetitive hormones in healthy postmenopausal women. CONCLUSION Since central adiposity in postmenopausal women was related to appetitive hormones, minimizing weight gain during the menopausal transition may optimize appetitive hormones, thereby facilitating appetite control and weight maintenance.