Biomedical subjects

W M Kohrt

Publications and source records attributed to W M Kohrt.

At least 19 recordsLinked to original sources

PubMed2005

Lower-body adiposity and metabolic protection in postmenopausal women.

CONTEXT: It has been suggested that the propensity to store fat in the gluteal-femoral region may be cardioprotective. OBJECTIVE: The primary aim of this study was to test whether the favorable associations of leg fat with risk factors for cardiovascular disease persist after controlling for the highly unfavorable effects of abdominal (visceral or sc) adiposity in postmenopausal women. STUDY PARTICIPANTS: The study included 95 postmenopausal women [age, 60 +/- 8 yr (mean +/- SD)]. MAIN OUTCOMES: Whole-body and regional fat distribution was measured using dual-energy x-ray absorptiometry and abdominal computed tomography. Markers of insulin resistance and dyslipidemia were determined from oral glucose tolerance tests and fasted lipid and lipoprotein measurements, respectively. Primary outcomes were: fasting insulin (INS0), area under the insulin curve (INS(AUC)), product of the oral glucose tolerance test insulin and glucose AUC (INS(AUC) - GLU(AUC)), serum triglycerides (TG), and high-density lipoprotein (HDL) cholesterol. RESULTS: Controlling for trunk fat revealed a favorable effect of leg fat on INS0, INS(AUC), INS(AUC) x GLU(AUC), TG, and HDL. However, after controlling for either visceral or sc abdominal adiposity, TG was the only risk factor for which the favorable effect of leg fat persisted. CONCLUSIONS: The lack of an association between leg fat and most of the risk factors, after adjusting for abdominal visceral or sc fat, suggests an overriding deleterious influence of abdominal adiposity on cardiovascular risk. Nevertheless, our finding that regional adipose tissue depots have apparent independent and opposing effects on serum TG supports the need for further research into the physiological mechanisms governing these effects.

Abdomen↗

PubMed2005

Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic--pituitary--adrenal axis activity.

OBJECTIVE: The aim of this study was to determine whether salivary cortisol measured by a simple enzyme immunoassay (EIA) could be used as a surrogate for serum total cortisol in response to rapid changes and across a wide range of concentrations. DESIGN: Comparisons of matched salivary and serum samples in response to dynamic hypothalamic-pituitary-adrenal (HPA) axis testing. Subjects Healthy women (n=10; three taking oral oestrogens) and men (n=2), aged 23--65 years, were recruited from the community. Measurements Paired saliva and serum samples were obtained during three protocols: 10 min of exercise at 90% of maximal heart rate (n=8), intravenous administration of corticotrophin-releasing hormone (CRH; n=4), and dexamethasone suppression (n=7). Cortisol was measured in saliva using a commercial high-sensitivity EIA and total cortisol was measured in serum with a commercial radioimmunoassay (RIA). Results The time course of the salivary cortisol response to both the exercise and CRH tests paralleled that of total serum cortisol. Salivary cortisol demonstrated a significantly greater relative increase in response to the exercise and CRH stimuli (697+/- 826%vs. 209+/- 150%, P=0.04 saliva vs. serum). A disproportionately larger increase in free cortisol, compared with total, would be expected when the binding capacity of cortisol-binding globulin (CBG) is exceeded. In response to dexamethasone suppression, relative decreases in cortisol were not significantly different between the two media (-47+/- 56%vs.-84+/- 8%, P=0.13 saliva vs. serum). Although a significant linear correlation was found for all paired salivary and serum total cortisol samples (n=183 pairs, r=0.60, P<0.001), an exponential model provided a better fit (r=0.81, P<0.001). The linear correlations were strengthened when data from subjects on oral oestrogens (n=52 pairs, r=0.75, P < 0.001) were separated from those not taking oestrogens (n=131 pairs, r=0.67, P<0.001). Conclusions Salivary cortisol measured with a simple EIA can be used in place of serum total cortisol in physiological research protocols. Evidence that salivary measures represent the biologically active, free fraction of cortisol includes: (1) the greater relative increase in salivary cortisol in response to tests that raise the absolute cortisol concentration above the saturation point of CBG; (2) the strong exponential relationship between cortisol assessed in the two media; and (3) the improved linear correlations when subjects known to have increased CBG were analysed separately. Thus, an advantage of measuring salivary cortisol rather than total serum cortisol is that it eliminates the need to account for within-subject changes or between-subject differences in CBG.

Adult↗

PubMed2004

Protection of bone mass by estrogens and raloxifene during exercise-induced weight Loss.

The aim of this study was to determine whether estrogen and/or raloxifene help to conserve bone mineral density (BMD) during moderate weight loss. Postmenopausal women (n = 68) participated in a 6-month weight loss program that consisted primarily of supervised exercise training. Another 26 women were studied over 6 months of weight stability. All participants were randomized to three treatment arms: placebo, raloxifene (60 mg/d), or hormone therapy (HT; conjugated estrogens, 0.625 mg/d; trimonthly medroxyprogesterone acetate, 5 mg/d for 13 d, for women with a uterus). Changes in body weight (mean +/- se) averaged 0.8 +/- 0.5 kg in the weight-stable group and -4.1 +/- 0.4 kg in the weight loss group. Across all measured skeletal sites, average changes in BMD in weight stable women were -0.6 +/- 1.1% (n = 7), 0.9 +/- 0.6% (n = 9), and 3.0 +/- 0.7% (n = 10) in the placebo, raloxifene, and HT groups, respectively; comparable BMD changes in the weight loss groups were -1.5 +/- 0.5% (n = 22), -0.5 +/- 0.5% (n = 23), and 1.1 +/- 0.4% (n = 23). There were no significant interactions between weight loss and drug treatment on changes in BMD, but there were significant main effects of weight loss on lumbar spine (P = 0.022), total hip (P = 0.010), and trochanter BMD (P < 0.001). These findings suggest that weight loss, even when modest in magnitude and induced by exercise training, causes a reduction in BMD, particularly in women not taking raloxifene or HT. It is not known whether reductions in BMD of this magnitude increase the risk for osteoporotic fracture.

Aged↗

PubMed2003

Intravenous estrogens increase insulin clearance and action in postmenopausal women.

To test the hypothesis that estrogens alter insulin action, we evaluated the effects of intravenous conjugated estrogens (CE) on insulin-stimulated steady-state glucose infusion rate (SSGIR) and suppression of plasma glycerol in postmenopausal women (mean +/- SD; 56 +/- 4 yr; n = 12) not using hormone replacement. SSGIR and glycerol were measured during a two-stage (8 and 40 mU. m-2. min-1) hyperinsulinemic euglycemic clamp on 2 days, with or without a 2.5-mg intravenous CE bolus. Serum estradiol concentrations were increased approximately 200% on the estrogen (EST) compared with the control (CON) days. Serum insulin was reduced (P < 0.01) during stage 2 of the clamp for EST (63.3 +/- 12.8 micro U/ml) vs. CON (78.2 +/- 15.8 micro U/ml). Mean SSGIR and plasma glycerol did not differ between CON and EST days. With adjustment for differences in insulin concentration between conditions, stage 2 glucose disposals were significantly higher (8.63 vs. 7.20 mg. kg-1. min-1) and plasma glycerol concentrations were significantly lower (29.4 vs. 35.0 micro mol/l) for EST vs. CON. Our findings suggest that acute CE administration increases insulin clearance and action in postmenopausal women.

Body Composition↗

PubMed2003

Effects of estrogen replacement on metabolic factors that influence physical performance in female hypogonadism.

There is a lack of knowledge regarding the effects of estrogens on physical performance. This is related, in part, to the challenge of isolating the effects of estrogens from those of progestins, because levels of both hormones fluctuate across the menstrual cycle, both decline during the menopausal transition, and the administration oh hormones to hypogonadal women typically involves a combination of estrogens and progestins. Some research findings suggest that fluctuations in estrogen levels acutely influence factors that may affect physical performance, such as substrate utilization or maximal aerobic power, but solid evidence is lacking. The simple observation that hypogonadism is not uncommon among elite athletes in some sports suggests that estrogen deficiency does not have a major negative impact on athletic performance. However, chronic hypogonadism may ultimately lead to impaired performance by menas that are not necessarily obvious. For example, chronic estrogen deficiency has potent, deleterious effects on the skeleton that can increase risk for stress fracture and may limit the ability to sustain a high level of physical training. Estrogen deficiency also appears to promote fat accumulation and may accelerate the loss of fat-free mass, and both of these changes in body composition could impair physical performance. There is evidence that hormone replacement attenuates the negative effects of hypogonadism on body composition and bone density, and that effects are mediated primarily by estrogens rather than progestins. Further research is necessary to broaden the understanding of the role of the estrogens in physical performance.

Adult↗

PubMed2002

Contributions of total and regional fat mass to risk for cardiovascular disease in older women.

The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.

Abdomen↗

PubMed2001

Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial.

CONTEXT: Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women. OBJECTIVE: To determine whether HRT increases bone mineral density (BMD) in frail elderly women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000. PARTICIPANTS: Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. INTERVENTION: Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months. MAIN OUTCOME MEASURES: The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. RESULTS: Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%). CONCLUSIONS: In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.

Absorptiometry, Photon↗

PubMed2001

Effects of hormone replacement therapy on serum lipids in elderly women. a randomized, placebo-controlled trial.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among older women. In observational studies, the incidence of CHD has been reduced in postmenopausal women who take hormone replacement therapy (HRT). A low serum level of high-density lipoprotein (HDL) cholesterol is one of the risk factors predictive of death from CHD. OBJECTIVE: To determine the effects of HRT on serum lipid and lipoprotein levels in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University research center. PARTICIPANTS: 59 sedentary women 75 years of age or older. INTERVENTION: Participants were assigned to 9 months of oral therapy with placebo or conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days. MEASUREMENTS: Serum lipid and lipoprotein levels. RESULTS: After 9 months of treatment, women in the HRT group compared with women in the placebo group had decreased low-density lipoprotein cholesterol levels (mean change [+/-SD], -0.47 +/- 0.69 mmol/L [-18.2 +/- 26.5 mg/dL] vs. -0.06 +/- 0.32 mmol/L [-2.2 +/- 12.2 mg/dL], respectively; between-group difference, 0.41 mmol/L [95% CI, 0.09 to 0.74 mmol/L], 16 mg/dL [95% CI, 3.5 to 28.5 mg/dL]; P = 0.01) and increased HDL cholesterol levels (mean change, 0.21 +/- 0.27 mmol/L [8.1 +/- 10.5 mg/dL] vs. 0.06 +/- 0.11 mmol/L [2.4 +/- 4.3 mg/dL], respectively; between-group difference, 0.15 mmol/L [CI, 0.008 to 0.29 mmol/L], 5.7 mg/dL [CI, 0.8 to 10.6 mg/dL]; P = 0.02). The observed changes were independent of age at menopause onset, baseline lipid values, body weight, waist circumference, percentage body fat, and peak aerobic power. CONCLUSIONS: In women 75 years of age or older, HRT improved the lipoprotein profile to the extent observed previously in younger postmenopausal women. Further studies are needed to evaluate whether these effects protect against CHD in this population.

Aged↗

PubMed2001

Effects of hormone replacement therapy on cognitive performance in elderly women.

OBJECTIVE: To determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older. METHODS: A 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests. RESULTS: At baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy. CONCLUSIONS: Although conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression.

Aged↗

PubMed2001

Modest lifestyle intervention and glucose tolerance in obese African Americans.

OBJECTIVE: Previous studies have demonstrated the benefit of short-term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short-term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. RESEARCH METHODS AND PROCEDURES: An intervention group (n = 45; 47 +/- 1 year [mean +/- SE]), 105 +/- 4 kg; body mass index: 39 +/- 1 kg/m(2)) received an energy-restricted diet (943 +/- 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (-125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C-peptide during an oral glucose tolerance test were measured at baseline, 1-week, and 4-month intervals. A control group (n = 24; 48 +/- 1 year; 110 +/- 5 kg; body mass index: 41 +/- 2 kg/m(2)) underwent these measurements at 4-month intervals. RESULTS: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1-week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: -4.6 +/- 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: -103 +/- 44 mM. min; p < 0.05 vs. control). DISCUSSION: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.

Adult↗

PubMed2001

Waist circumference vs body mass index for prediction of disease risk in postmenopausal women.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women. DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine. SUBJECTS: A total of 323 healthy postmenopausal (66+/-5 y; mean+/-s.d.) women not using any hormone replacement. MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol. RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m(2)) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24--28 kg/m(2)). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size. CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Adipose Tissue↗

PubMed2001

Osteoprotective benefits of exercise: more pain, less gain?

Based on the results of their study, Hagberg et al. suggested that physical activity that is moderate in intensity might be most appropriate for the prevention of osteoporosis in postmenopausal women. The take-home message is that being physically active has osteoprotective benefits. However, the implication that more vigorous exercise is less beneficial must be carefully scrutinized. When compared with the physically active nonathletes, the highly trained athletes in this study tended to be more years beyond menopause, had been on HRT for a smaller proportion of the postmenopausal period, and may have had lower endogenous estrogen levels as a result of having less fat mass. The chronic exposure of the skeleton to estrogens very likely played a more prominent role in determining BMD status in the women in this study than the investigators were able to ascertain, owing largely to the cross-sectional nature of the investigation. It is safe to conclude that an exercise prescription for the prevention of osteoporosis should include weight-bearing exercise, but the optimal intensity, frequency, and duration of exercise remain to be established. The results of the study by Hagberg et al. emphasize the importance of physical activity for sustaining BMD, but should not provide a basis for discouraging women from performing vigorous exercise.

Aged↗

PubMed2001

Frail older women's participation in a trial of hormone replacement therapy: perceived benefits and concerns.

OBJECTIVE: The aim of this study was to identify the reasons that were important to frail older women's decisions to participate or not participate in a clinical trial of hormone replacement therapy (HRT). DESIGN: We conducted a cross-sectional study of a community-based sample of physically frail women > or = 75 years old, who were recruited to participate in an intervention trial of HRT. Participants were randomized 2:1 to either HRT or placebo, respectively. Questionnaires measured participants' reasons for participation and nonparticipants' reasons for declining. Five-point scaled responses to questionnaire items ranged from least to most important or least to most concerned. RESULTS: Sixty-nine women participated (84% white, 16% African American) in the trial. Nonparticipants (n = 41) were older, on average, than participants (83.8+/-4.2 vs. 82.2+/-3.6 years; p = 0.04). Important reasons for participation were reducing risk for Alzheimer's disease and osteoporosis, having more energy, improving self-care ability, and benefiting other women. Fear of cancer from postmenopausal estrogen was the predominant concern of 46% of nonparticipants and 78% of participants (p = 0.08). Recommendation against participation or use of estrogen by a woman's personal physician was the most prevalent additional reason given for nonparticipation. CONCLUSIONS: Disease prevention and improving self-care abilities were most important to participants. Fear of cancer was not a greater concern for nonparticipants than for participants. The role of the physician in older women's decision-making about use of postmenopausal estrogen seems to be important.

Aged↗

PubMed2001

Aging and the osteogenic response to mechanical loading.

The osteogenic response to mechanical stress is blunted with aging. It has been postulated that this decline in responsiveness is related to (a) a limited ability to engender the strain necessary to reach the bone modeling threshold, due to decreased muscle mass and strength, and/or (b) a decline in certain hormones or growth factors that may interact with mechanical signals to change the sensitivity of bone cells to strain. There is reason to believe that both of these factors contribute to the reduced ability to increase bone mass through exercise with advancing age. Weight-bearing endurance exercise and resistance exercise have both been found to increase bone mass in older women and men. However, exercise training studies involving older individuals have generally resulted in increased bone mineral density only when the exercise is quite vigorous. There is also evidence that the osteogenic response to mechanical loading is enhanced by estrogens. Whether age-related changes in other factors (e.g., other hormones, growth factors, cytokines) also contribute to the reduced responsiveness of the aged skeleton to mechanical loading remains to be investigated.

Aging↗

PubMed2001

Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women.

The independent and combined effects of exercise training and hormone replacement therapy (HRT) on body composition, fat distribution, glucose tolerance, and insulin action were studied in postmenopausal women, aged 68 +/- 5 yr, assigned to control (n = 19), exercise (n = 18), HRT (n = 15), and exercise + HRT (n = 16) groups. The exercise consisted of 2 mo of flexibility exercises followed by 9 mo of endurance exercise. HRT was conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Total and regional body composition were measured by dual-energy X-ray absorptiometry. Serum glucose and insulin responses were measured during a 2-h oral glucose tolerance test. There were significant main effects of exercise on reductions in total and regional (trunk, arms, legs) fat mass, increase in leg fat-free mass, and improvements in glucose tolerance and insulin action. There were significant main effects of HRT on the reduction of total fat mass (HRT, -3.0 +/- 4.0 kg; no HRT, -1.3 +/- 2.6 kg), with a strong trend for reductions in trunk and leg fat mass (both P = 0.07). There was also a significant improvement in insulin action in response to HRT. These results suggest that there are independent and additive effects of exercise training and HRT on the reduction in fat mass and improvement in insulin action in postmenopausal women; the effect of HRT on insulin action may be mediated, in part, through changes in central adiposity.

Adipose Tissue↗

PubMed2001

Acute exercise effect on postabsorptive serum leptin.

We postulated that high circulating cortisol levels during intense exercise would lead to increased serum leptin concentrations. Young, lean men ate a small meal and then exercised on a cycle ergometer for 41 min or rested on a control day. Serum leptin concentration was 10% greater during exercise than in the control condition (P < 0.05). Directly after exercise, serum leptin dropped to approximately 10% less than the control level (P < 0.05) but had recovered to the nonexercised level after approximately 2 h of recovery. Rapid exercise effects on circulating leptin were related to changes in hemoconcentration rather than changes in leptin mass. When serum leptin was normalized to serum protein, leptin increased by 10% in the exercise condition compared with control by the end of recovery (P < 0.05). Although exercise increased serum cortisol concentration threefold, there was no relation between differences in cortisol and exercise vs. control differences in normalized leptin. The increased leptin mass after exercise may have been related to greater plasma glucose concentration during recovery after exercise compared with the control condition.

Adult↗

PubMed2000

Effects of DHEA replacement on bone mineral density and body composition in elderly women and men.

OBJECTIVE: Dehydroepiandrosterone (DHEA) is a precursor for both oestrogens and androgens. Its marked decline with ageing may influence age-related changes in tissues influenced by sex hormones. The aim of this study was to determine the effects of DHEA replacement on bone mineral density (BMD) and body composition in elderly women and men with low serum DHEA sulphate (DHEAS) levels. DESIGN: Prospective 6 month trial of oral DHEA replacement, 50 mg/day. PATIENTS: Experimental subjects were 10 women and eight men, aged 73 +/- 1 years. Control subjects were 10 women and eight men, aged 74 +/- 1 years. MEASUREMENTS: BMD, body composition, serum markers of bone turnover, serum lipids and lipoproteins, oral glucose tolerance, serum IGF-I, total serum oestrogens and testosterone. RESULTS: BMD of the total body and lumbar spine increased (mean +/- SEM; 1.6 +/- 0.6% and 2.5 +/- 0.8%, respectively; both P < or = 0.05), fat mass decreased (- 1.3 +/- 0.4 kg; P < 0.01) and fat-free mass increased (0.9 +/- 0.4 kg; P < or = 0. 05) in response to DHEA replacement. DHEA replacement also resulted in increases in serum IGF-I (from 108 +/- 8 to 143 +/- 7 microg/l; P < 0.01) and total serum testosterone concentrations (from 10.7 +/- 1.2 to 15.6 +/- 1.8 nmol/l in the men and from 2.1 +/- 0.2 to 4.5 +/- 0.4 nmol/l in the women; both P < or = 0.05). CONCLUSIONS: The results provide preliminary evidence that DHEA replacement in those elderly women and men who have very low serum DHEAS levels can partially reverse age-related changes in fat mass, fat-free mass, and BMD, and raise the possibility that increases in IGF-I and/or testosterone play a role in mediating these effects of DHEA.

Adjuvants, Immunologic↗

PubMed2000

Low-intensity exercise as a modifier of physical frailty in older adults.

OBJECTIVE: To examine the effects of a 3-month low-intensity exercise program on physical frailty. DESIGN: Randomized clinical trial. SETTING: Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center. PARTICIPANTS: Eighty-four physically frail older adults (mean age, 83 +/- 4 yrs). INTERVENTION: Three-month low-intensity supervised exercise (n = 48) versus unsupervised home-based flexibility activities (n = 36). MAIN OUTCOME MEASURES: Physical performance test, measures of balance, strength, flexibility, coordination, speed of reaction, peripheral sensation. RESULTS: Significant improvement was made by the exercise group on our primary indicator of frailty, a physical performance test (PPT) (29 +/- 4 vs 31 +/- 4 out of a possible 36 points), as well as many of the risk factors previously identified as contributors to frailty; eg, reductions in flexibility, strength, gait speed, and poor balance. Although the home exercise control group showed increases in range of motion, the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT. CONCLUSIONS: Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults. They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty. Although results suggest that frailty is modifiable, it is not likely to be eliminated with exercise, and efforts should be directed toward preventing the condition.

Aged↗