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.     

The 6-minute walk is associated with frailty and predicts mortality in older adults with heart failure

Heart failure (HF) may contribute to the development of functional decline and frailty in older adults. Sixty HF patients with an ejection fraction ≤ 40% evaluated in 2004 and 2005 were reevaluated in 2008. Six-minute walk distance (6MW), frailty score, and biomarkers (25-hydroxyvitamin D, C-reactive protein, and interleukin-6 [IL-6]) were measured. Participants were categorized at baseline and follow-up into 3 groups: nonfrail/normal endurance (NF/NE), nonfrail/low endurance (NF/LE) and frail/low endurance (F/LE). Survival time was assessed according to frailty/endurance status and associated predictors of mortality. Forty-three men, 17 women (mean age, 78 ± 12 years) were contacted. At follow-up, 20 had died, 20 participated, and 20 did not participate. There were no changes in frailty/endurance status over time (McNemar;P=.19). Deaths occurred in 18% of NF/NE, 45% of NF/LE, and 60% of F/LE persons. The NF/NE group had greater survival rates than the NF/LE ( P=.032) and F/LE ( P=.014) groups. The 6MW and frailty score were independently predictive of mortality, with hazard ratios of 0.82 (95% confidence interval, 0.72-0.94) and 1.64 (95% confidence interval, 1.19-2.26), respectively, as was New York Heart Association class and IL-6. Backward stepwise Cox regression revealed that 6MW and frailty each were associated with mortality (P=.005) and highly correlated. Physical function is an important predictor of mortality in older adults with HF. The 6MW may be useful as a measure of frailty.     

Dementia care consultation for family caregivers: Collaborative model linking an Alzheimer's association chapter with primary care physicians

Objective: The primary objective is to report on the efficacy of an individualized dementia care consultation intervention for family caregivers of patients with diagnosed dementia living in the community. The secondary objective is to present evidence on the intervention process to inform the feasibility and sustainability of the model featuring collaboration between primary care physicians and a voluntary sector organization.

Method: Randomization was based on primary care physician practice site. In the intervention group, dementia care consultants located at an Alzheimer's association chapter provided individualized counseling and support over a 12-month period, and sent copies of care plans developed with family caregivers to referring primary care physicians. In the control group, family caregivers received educational and community resource information but no care consultation. Nursing home admission of patients during the 12-month study period was the primary outcome; secondary outcomes included measures of caregiver self-efficacy for managing dementia, caregiver depressive symptoms, and caregiver burden.

Results: A total of 84 family caregivers participated. After adjusting for baseline characteristics, patients whose family caregivers were in the intervention group were less likely than their control group counterparts to be admitted to a nursing home (Adjusted odds ratio = 0.40; 95% C.I. = 0.14–1.18; p = 0.10). No other outcomes were significantly different between treatment groups; however, intervention group caregivers reporting greater satisfaction with the intervention showed improved self-efficacy for managing dementia compared to their less satisfied counterparts. Medical record reviews found that care plans were found in most patient records, but that only 27% of intervention group caregivers reported discussing these care plans with physicians. Three different individuals occupied the dementia care consultant position during the study period, and this turnover led to family caregiver dissatisfaction.

Conclusion: The dementia care consultation intervention showed favorable effects on nursing home admission and on caregiver outcomes among intervention group caregivers more satisfied with the intervention, but there are important barriers to sustaining this collaboration between primary care physicians and a voluntary sector organization such as an Alzheimer's association chapter.     

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.     

Association between level of frailty and bone mineral density in community-dwelling men.

The goal of this study is to determine the associations between the components of a frailty definition and bone mineral density (BMD) in older men. A total of 392 community dwelling men (age range: 58-95 yr) with a mean age of 73+/-8 yr were evaluated. Femoral neck BMD T-scores ranged from -5.78 to +2.50, with 48.7% who had T-scores between -1 and -2.5 (low bone mass) and 8.7% who had T scores < or = -2.5 (osteoporosis). Participants were characterized as normal (39%), intermediate (55%), or frail (6%). Hand grip strength was 31.5+/-9.1 kg in those with normal BMD compared with 26.5+/-7.9 kg in those with osteoporotic BMD (p=0.0026). Walk speed (8 ft) was 2.32+/-0.49 s in those with normal BMD compared with 2.87+/-1.30 s with osteoporotic BMD (p=0.0015). Femoral neck T-score declined significantly with increasing level of frailty (p=0.014), but significance of decline was lost when corrected for age. Increasing frailty was associated with lower femoral neck BMD, although the association was not independent of age. Two components of the frailty model (i.e., hand grip strength and walking speed) were independently associated with lower femoral neck BMD, a finding that has not previously been reported in men.     

Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen. The objective of this study was to determine the prevalence of sarcopenia in a population of older, nonobese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT). METHODS: We measured appendicular skeletal muscle mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to 78 years old who had been using ERT for at least 2 years (mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia as an adjusted appendicular skeletal muscle mass (ASM) (mass divided by height squared) more than 2 SDs below the mean for a young healthy reference population. Health and menopause history were obtained. Body mass index (BMI) was calculated, and physical activity and performance were measured using the Physical Activity Scale in the Elderly, the chair rise time, the 6-minute walk, and measures of lower extremity strength and power. Serum estrone, estradiol, testosterone, and sex hormone binding globulin were measured. RESULTS: The prevalence of sarcopenia in nonobese, community-dwelling women who were long-term ERT users was 23.8%. Skeletal muscle mass correlated significantly with BMI, age at the time of starting ERT, hand grip strength, lower extremity strength and power, and testosterone level, but not with estradiol level. In linear regression analysis, BMI, leg press strength, and testosterone level contributed to adjusted ASM, accounting for 48.7% of the variance (p <.001). CONCLUSIONS: Sarcopenia is as common in nonobese women who are long-term ERT users as in community-dwelling women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. BMI, strength, and testosterone level contributed to appendicular skeletal mass in women. These data suggest that interventions to target nutrition, strength training, and testosterone replacement should be further investigated for their role in preventing muscle loss with age.     

Dehydroepiandrosterone Combined with Exercise Improves Muscle Strength and Physical Function in Frail Older Women

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women. DESIGN: Double‐blind, randomized, placebo‐controlled trial. SETTING: A major medical institution. PARTICIPANTS: Ninety‐nine women (mean age 76.6 ± 6.0) with low sulfated DHEA (DHEAS) levels, low bone mass, and frailty. INTERVENTION: Participants received 50 mg/d DHEA or placebo for 6 months; all received calcium and cholecalciferol. Women participated in 90‐minute twice‐weekly exercise regimens. MEASUREMENTS: Hormone levels, bone mineral density (BMD), bone turnover markers, body composition, upper and lower extremity strength, physical performance. RESULTS: Eighty‐seven women (88%) completed 6 months. There were no significant changes in BMD or bone turnover markers. DHEA supplementation resulted in gains in lower extremity strength (from 459 ± 121 N to 484 ± 147 N; P=.01). There was also improvement in Short Physical Performance Battery score, a composite score that focuses on lower extremity function, in those taking DHEA (from 10.1 ± 1.8 to 10.7 ± 1.9; P=.02). There were significant changes in all hormone levels, including DHEAS, estradiol, estrone, and testosterone, and a decline in sex hormone‐binding globulin levels in those taking DHEA. CONCLUSION: DHEA supplementation improved lower extremity strength and function in older, frail women involved in a gentle exercise program of chair aerobics or yoga. No changes were found in BMD either due to small sample size, short duration of study or no effect. The physical function findings are promising and require further evaluation as frail women are at high risk for falls and fracture.     

Preventive vaccines against bioterrorism: evaluation of efficacy and safety

This paper discusses the US Food and Drug Administration's approach to evaluation of vaccines in general, and vaccines against diseases of bioterrorism in particular. We summarize the scientific bases for development and approval of vaccines and then discuss specific issues regarding vaccines against disease organisms that could potentially be used as weapons of bioterrorism.