Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial.

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (-5.9%, P = .02; -7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol.

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial.

BACKGROUND: Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE: Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. DESIGN: We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS: Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS: Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.

The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women.

OBJECTIVES: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women. DESIGN: Randomized, placebo-controlled trial conducted for 3 years. SETTING: Academic health center in greater Hartford, Connecticut. PARTICIPANTS: Fifty-seven healthy, community-dwelling, older postmenopausal women. INTERVENTION: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MEASUREMENTS: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression. RESULTS: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age. CONCLUSION: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.

Adherence to calcium/vitamin D and estrogen protocols among diverse older participants enrolled in a clinical trial.

PURPOSE: This study was intended to identify characteristics of those who adhere poorly to calcium/vitamin D and estrogen replacement protocols, and aimed to assess the effects of ethnicity, socio-economic status, and health status on medication adherence. METHODS: The adherence rates of 107 older white, African American and Hispanic participants of a clinical trial involving calcium/vitamin D and either estrogen replacement or placebo therapy were analyzed. Structural equation modeling was used to test the hypothesis that minority participants would have lower adherence rates than white participants, but only if they had lower household incomes and educational achievement, more osteoporosis risk factors, negative health assessments, and fewer somatic complaints than white participants. RESULTS: The average age of participants was 76 years. Minority participants and those with lower SES had lower adherence rates than white participants and those with higher SES. Plausible models that met goodness-of-fit criteria showed that the estrogen/placebo adherence rates were affected directly by being African American or Hispanic and the SF-36 mental health score, and indirectly by somatic complaints. History of fracture and household income directly predicted calcium/vitamin D adherence rates. CONCLUSION: Efforts to improve adherence to medical regimens should consider differences in adherence behaviors based on ethnicity, SES, and mental health.

Impact of smoking cessation on bone mineral density in postmenopausal women.

BACKGROUND: Although clinical guidelines recommend smoking cessation to improve bone health, the impact of short-term smoking cessation (i.e., 1 year) on bone mineral density (BMD) is not known. We examined the effects of smoking cessation on BMD measurements, markers of bone turnover, and hormone profiles in postmenopausal women. METHODS: Postmenopausal women (n = 152) who smoked at least 10 cigarettes per day were randomly assigned to behavioral counseling and either nicotine or placebo patch for smoking cessation (3-month treatment with a 1-month taper) and followed for an additional year. The BMD at various sites (hip, spine, wrist, and total body), serum and urine biochemical markers of bone turnover, and sex hormones were measured at baseline and again 1 year after smoking treatment. Women who continuously abstained from smoking between the end of treatment and 1 year later (quitters) (n = 42) were compared with women who completed the study and continued to smoke (n = 77). RESULTS: Femoral trochanter BMD increased by 2.9% among quitters vs. 0.6% among continued smokers (p = 0.02). Total hip BMD increased by 1.52% among quitters vs. 0.43% among continued smokers (p = 0.03). Changes in BMD at the femoral neck, radius, spine, and total body did not significantly differ between groups. The effects of smoking cessation on bone were mediated in part by weight gain. Smoking cessation was also associated with an increase in bone alkaline phosphatase. CONCLUSIONS: Smoking cessation, relative to continued smoking, increases BMD at the femoral trochanter and total hip in postmenopausal women.

Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women.

OBJECTIVES: To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women. DESIGN: Double-blind, placebo-controlled trial. SETTING: Clinical research center in Connecticut. PARTICIPANTS: Healthy, community-dwelling women aged 65 and older (n=167). INTERVENTION: Eligible women were randomly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months. All women (estradiol or placebo) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months. All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day. MEASUREMENTS: Appendicular skeletal muscle mass (ASM), lean body mass (LBM), and percentage body fat were measured using dual x-ray absorptiometry. Sarcopenia was defined as skeletal muscle mass (ASM/height2) 2 standard deviations or less than young, healthy reference population mean. Physical activity (Physical Activity Scale in the Elderly (PASE)) and performance were measured. Serum estrone, estradiol, and sex hormone-binding globulin were measured. RESULTS: The prevalence of sarcopenia at baseline was 13%. There were no baseline differences between groups except for PASE score and chair rise time, in which the estrogen group had better performance. No changes in ASM, LBM, percentage of body fat, or physical performance were found after 3 years of estrogen therapy. CONCLUSION: Sarcopenia was present in 13% of this group of community-dwelling, postmenopausal older women. Ultra-low-dose estrogen therapy neither improves nor harms ASM. Similarly, no changes in body fat or physical performance were detected.

Low-dose estradiol alters brain activity.

Although several studies have examined the effects of estrogen replacement therapy (ERT) on neural activity associated with tasks of learning and memory, no study has examined such effects on a sustained attention task. This study examined the effect of low-dose estrogen replacement therapy on hemodynamic activity elicited by a visual three-stimulus oddball task recorded using event-related functional magnetic resonance imaging (fMRI). Participants included 16 women between the ages of 73 and 84 who were part of a randomized controlled double-blind study to evaluate the effect of an ultralow dose micronized estradiol on bone. No significant differences in behavioral performance were found with ERT. However, there was evidence that ERT group participants had both reductions and increases in the amplitude of hemodynamic response in a variety of subcortical and cortical brain regions. These included regions involved in perception and attention such as the occipital and parietal lobes, motor cortex, anterior cingulate and prefrontal cortex. These findings suggest that estrogen may facilitate the efficiency of brain function during the performance of sustained attention tasks in post-menopausal elderly women.

Osteoporosis medications used by older African-American women: effects of socioeconomic status and psychosocial factors.

This study examined the effects of socioeconomic status, knowledge and Health Belief Model variables on ever use of hormone therapy and other osteoporosis medications among older African-American women. One-hundred and two African-American women, 60 years old or older, randomly selected from Registers of Voters and a list of participants in educational activities of a university hospital, were interviewed in their homes. Data collected concerned knowledge of osteoporosis, Health Belief Model variables, and cues to action such as history of hysterectomy, personal and family history of cancer, bone mineral density testing, and discussion with a physician about osteoporosis. Socioeconomic status indicators included years of education and household income. The average respondent age was 71.1 years; 47% were current or previous users (ever users) of hormone therapy, and 11% were ever users of other osteoporosis medications. Knowledge of osteoporosis, (odds ratio = 1.4), Hormone therapy benefits, (odds ratio = 1.63), a hysterectomy (odds ratio = 4.35), and a family history of cancer (odds ratio = 4.0) increased the odds of ever using hormone therapy. Perceptions of susceptibility (odds ratio = 3.5) and discussion with a physician about osteoporosis (odds ratio = 6.4) increased odds of ever using other osteoporosis medications. Socioeconomic status mediated the effects of knowledge of osteoporosis on ever using hormone therapy. Efforts to promote bone health to older African-American women should focus primary efforts to increasing perceptions of susceptibility to fracture and persuading physicians to initiate discussions about fracture prevention with African-American patients before a fracture occurs.

Bone health and aging: implications for menopause.

Osteoporosis is one major health condition that contributes to excess morbidity and mortality in women after menopause. In the past, hormone therapy (HT) was prescribed commonly for symptoms of menopause, and there was also evidence that HT protected against osteoporosis. Recently, however, the overall health risks have been reported to exceed benefits, with the beneficial effects seen only in the decreased incidence of hip fractures and colon cancer. The role of HT in menopausal women is unclear at this time, although many women may require it to reduce menopausal symptoms. Osteoporosis may be an area where the benefit of using HT may outweigh the risks in a select group of women. Further, because lower than usual doses of estrogen have been shown to reduce menopausal symptoms and to protect bone, additional research will likely expand physicians' current knowledge of the use of HT in menopausal women. This article reviews the use of low-dose estrogen to promote bone health in postmenopausal women.

The effect of different doses of micronized 17beta-estradiol on C-reactive protein, interleukin-6, and lipids in older women.

BACKGROUND: The authors evaluated the effect of 3 doses (0.25 mg/day, 0.5 mg/day, and 1 mg/day) of micronized 17beta-estradiol (E2) on C-reactive protein (CRP), interleukin-6 (IL-6), and lipids, compared with placebo, in healthy older women participating in an osteoporosis study. METHODS: This randomized, double-blind, placebo-controlled study was conducted in a University clinical research center. Participants were healthy, community-living women older than 65 years. The primary outcome measure of the study was bone metabolism as estimated by serum and urine markers of bone turnover. For this analysis, the authors measured serum markers of CRP, IL-6, lipids, intracellular adhesion molecule-1, and E-selectin at baseline, after 12 weeks of treatment, and after 12 weeks with no treatment. RESULTS: A significant dose-response effect of estrogen occurred on CRP levels. After 12 weeks of treatment, CRP decreased 59% in the 0.25 mg/day E2 group and increased 65% in the 1 mg/day E2 group, compared with placebo. The CRP level continued to be elevated (92%), compared with placebo, 12 weeks after treatment was discontinued in the 1 mg/day E2 group. High-density lipoprotein (HDL) and HDL2 cholesterol increased and low-density lipoprotein (LDL) cholesterol decreased at 12 weeks in the 1 mg/day E2 group, with a significant dose-response effect. E-selectin decreased significantly in the 1 mg/day E2 group 12 weeks after discontinuation of treatment (-7%), and there was a significant dose-response effect at this time. The 2 lower doses did not affect any of these parameters. Total and HDL3 cholesterol, triglycerides, lipoprotein(a), intracellular adhesion molecule-1, and IL-6 did not change with any dose of E2. CONCLUSIONS: C-reactive protein, an inflammation marker associated with increased risk for cardiovascular disease, decreased in women taking the lowest estrogen dose but increased in women assigned to the highest estrogen dose, suggesting decreased inflammation with lower dose E2. However, with 3 months of treatment, 0.25 or 0.5 mg/day E2 did not have the same beneficial effects on HDL or LDL cholesterol as did 1 mg/day E2. These data suggest that estradiol doses have differential short-term effects on markers of cardiovascular disease. Low-dose E2 decreased CRP, an important marker of inflammation, but did not affect lipid parameters, whereas the highest dose increased CRP and had a beneficial effect on lipid parameters. The long-term consequences of these effects are unknown, but it is possible that estradiol dose should be considered when risk:benefit ratios are evaluated for individual women before estrogen replacement therapy is initiated.

Strategies for enrolling diverse older women in an osteoporosis trial.

OBJECTIVES: This study reviewed a consumer-oriented process for recruiting research volunteers age 65 or older for an osteoporosis clinical trial. METHODS: Odds ratios were used to estimate the relative importance of methods to enroll research volunteers from three racial or ethnic groups. RESULTS: Nine hundred and four women were screened; 168 African American, White, and Hispanic women enrolled. Mailings and media were effective when the target population was large and knowledgeable about the disease and treatment being investigated. Efficiency of mailings was increased when individuals in the mailing list were familiar with research and the research center. An interpersonal approach was more effective than a media-based approach when the target population was small, unaware of their personal risk of the disease, and unfamiliar with research and research center. DISCUSSION: Information on the characteristics of potential volunteers and their communities will enable readers to evaluate the applicability of recruitment methods used.

Multicultural medication adherence: a comparative study.

The purpose of this study was to evaluate the effect of several interventions on improving medication adherence among White, Black, and Hispanic older women. A total of 109 women older than age 65 who were participating in a clinical osteoporosis trial were recruited for this 12-month study examining medication adherence. After baseline medication adherence was assessed, participants underwent standardized teaching. Participants were contacted monthly by telephone and were seen in a clinic setting every 3 months. All participants used a pillbox for 6 months, and the minority women used an electronic monitoring bottle for 6 months. Adherence was highest in White women. Black women showed significant improvement in adherence at 9 and 12 months, and Hispanic women demonstrated a significant increase in adherence at 12 months. The use of electronic monitors had a positive effect on adherence for the minority women.

Barriers to eligibility and enrollment among older women in a clinical trial on osteoporosis: effects of ethnicity and SES.

OBJECTIVES: The study examined whether ethnicity or socioeconomic status influenced a group's ability to meet eligibility criteria and willingness to enroll. METHOD: The eligibility and enrollment status of 904 women aged 65 years and older who responded to recruitment efforts of an estrogen and osteoporosis clinical trial were analyzed. RESULTS: Among women screened, 59% were White, 27% African Americans, and 14% Hispanics; average age was 75 years; 57.6% were eligible, of which 32% enrolled. High-income area residents were more likely to be eligible than low-income residents. African Americans were less likely to be eligible for medical reasons than non-African Americans. Eligible Hispanics were more likely to be enrolled than non-Hispanics. African Americans were equally willing to enroll as Whites. Minority residents of low-income areas were more likely to enroll than minority residents of high-income areas. DISCUSSION: Recruitment efforts should address barriers to eligibility and barriers to willingness to enroll.

The effect of raloxifene on markers of bone turnover in older women living in long-term care facilities.

OBJECTIVES: To examine the effect of raloxifene on bone turnover in elderly women. DESIGN: Clinical intervention. SETTING: Long-term care facilities. PARTICIPANTS: Nineteen women completed the study, mean age 85 (range 76-99). INTERVENTION: Raloxifene 60 mg was given daily for 12 weeks. MEASUREMENTS: Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate-resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point. RESULTS: Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P<.01), and serum TRAP 5b by 10% (P<.05) on treatment. CONCLUSION: Raloxifene reduces bone turnover in elderly women living in long-term care facilities. The effect of raloxifene on bone turnover is comparable with that seen in younger postmenopausal women.

Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women.

Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C-telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.

Osteoporosis in older men and women.

Hip fracture incidence accelerates approximately 10 years following the menopause in women and after age 70 in men. Approximately one million Americans suffer fragility fractures each year at a cost of over 14 billion dollars. The disability, mortality and cost of hip and vertebral fractures are substantial in the rapidly growing aging population so that prevention of osteoporosis is a major public health concern. Bone mineral density (BMD) measurement is used to make the diagnosis of osteoporosis prior to incident fracture, and to predict fracture risk. Recommendations for treatment and prevention of osteoporosis based on bone mineral density score published by the World Health Organization and the National Osteoporosis Foundation are outlined.