Richard N. Baumgartner

Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men

Cross-sectional studies have demonstrated a decline in testosterone and free and bioavailable testosterone with age. This occurs in a majority of older persons without an increase in luteinizing hormone (LH), suggesting that a component of the testosterone decrease is due to secondary hypogonadism. To determine whether these findings could be duplicated in a longitudinal study, we measured testosterone, LH, follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels in 77 men participating in the New Mexico Aging Process Study who had sera available in 1980 or 1981 and two or more serial samples in 1982, 1984, 1989, and/or 1994. Thirty-nine subjects had samples available from both 1980 and 1994. The age at entry into the study ranged from 61 to 87 years. Testosterone levels decreased over the 15 years of the study. In persons who were alive for the duration of the study, testosterone levels were significantly lower 5 years before termination of the study (P < .05). Testosterone levels did not differ at entry into the study among those who died and those who were alive at the end of the study period. Eight of 77 subjects (10%) had LH levels above the normal range at some time during the study. In contrast, 43% of subjects had elevated FSH levels. Both LH and FSH increased significantly with age. SHBG levels were measured in 1980 and 1994 and increased significantly with age (P < .0001). LH and FSH were highly correlated with one another, but neither correlated with testosterone. This study demonstrated a longitudinal decline in testosterone and an increase in LH and FSH in older men. The average rate of decrement in testosterone concentration was 110 ng/dL every decade.

Predictors of skeletal muscle mass in elderly men and women.

BACKGROUND Elderly men and women lose muscle mass and strength with increasing age. Decreased physical activity, hormones, malnutrition and chronic disease have been identified as factors contributing to this loss. There are few data, however, for their multivariate associations with muscle mass and strength. This study analyzes these associations in a cross-sectional sample of elderly people from the New Mexico Aging Process Study. METHODS Data collected in 1994 for 121 male and 180 female volunteers aged 65-97 years of age enrolled in The New Mexico Aging Process Study were analyzed. Body composition was measured using dual energy X-ray absorptiometry; dietary intake from 3 day food records; usual physical activity by questionnaire; health status from annual physical examinations; and serum testosterone, estrone, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF1) from radioimmunoassays of fasting blood samples. Statistical analyses included partial correlation and stepwise multiple regression. RESULTS The muscle mass and strength (adjusted for knee height) decreased with increasing age in both sexes. The muscle mass was significantly associated with serum free-testosterone, physical activity, cardiovascular disease, and IGF1 in the men. In the women, the muscle mass was significantly associated with total fat mass and physical activity. Age was not associated significantly with muscle mass after controlling for these variables. Grip strength was associated with age independent of muscle mass in both sexes. Estrogen (endogenous and exogenous) was not associated with muscle mass or strength in women. CONCLUSIONS Age-related loss of muscle mass and strength occurs in relatively healthy, well-nourished elderly men and women and has a multifactorial basis. Sex hormone status is an important factor in men but not in women. Physical activity is an important predictor of muscle mass in both sexes.

One‐Leg Balance Is an Important Predictor of Injurious Falls in Older Persons

OBJECTIVE: To test the hypothesis that one‐leg balance is a significant predictor of falls and injurious falls.

SARCOPENIA: ITS ASSESSMENT, ETIOLOGY, PATHOGENESIS, CONSEQUENCES AND FUTURE PERSPECTIVES

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study.

Increased body weight at the time patients are diagnosed with breast carcinoma has been associated with an increased risk of recurrence and reduced survival. Weight gain also is common after diagnosis. Increasing physical activity (PA) after diagnosis may minimize these adverse outcomes. In this population‐based study, the authors investigated whether PA levels after diagnosis declined from prediagnosis levels and whether any changes in PA varied by disease stage, adjuvant treatment, patient age, or body mass index (BMI) in 812 patients with incident breast carcinoma (from in situ to Stage IIIa).

Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients

PURPOSE Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. PATIENTS AND METHODS We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). CONCLUSION Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.

Influence of Pre- and Postdiagnosis Physical Activity on Mortality in Breast Cancer Survivors: The Health, Eating, Activity, and Lifestyle Study

PURPOSE To investigate the association between pre- and postdiagnosis physical activity (as well as change in prediagnosis to postdiagnosis physical activity) and mortality among women with breast cancer. PATIENTS AND METHODS This was a prospective observational study of 933 women enrolled onto the Health, Eating, Activity, and Lifestyle Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or September 2004, whichever came first. The primary outcomes measured were total deaths and breast cancer deaths. The primary exposures were physical activity in the year before and 2 years after diagnosis and the pre- to postdiagnosis change in physical activity. RESULTS Compared with inactive women, the multivariable hazard ratios (HRs) for total deaths for women expending at least 9 metabolic equivalent hours per week (approximately 2 to 3 h/wk of brisk walking) were 0.69 (95% CI, 0.45 to 1.06; P = .045) for those active in the year before diagnosis and 0.33 (95% CI, 0.15 to 0.73; P = .046) for those active 2 years after diagnosis. Compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45% lower risk of death (HR = 0.55; 95% CI, 0.22 to 1.38), and women who decreased physical activity after diagnosis had a four-fold greater risk of death (HR = 3.95; 95% CI, 1.45 to 10.50). CONCLUSION Moderate-intensity physical activity after a diagnosis of breast cancer may improve prognosis.

Changes in Body Fat and Weight After a Breast Cancer Diagnosis: Influence of Demographic, Prognostic, and Lifestyle Factors

PURPOSE Obese women and women who gain weight after a breast cancer diagnosis are at a greater risk for breast cancer recurrence and death compared with lean women and women who do not gain weight after diagnosis. In this population-based study, we assessed weight and body fat changes from during the first year of diagnosis to during the third year after diagnosis, and whether any changes in weight and body fat varied by demographic, prognostic, and lifestyle factors in 514 women with incident Stage 0-IIIA breast cancer. METHODS Patients were participants in the Health, Eating, Activity, and Lifestyle (HEAL) study. Weight and body fat (via dual-energy x-ray absorptiometry scans) were measured during the baseline visit and 2 years later at a follow-up visit. Analysis of covariance methods were used to obtain mean weight and body fat changes adjusted for potential cofounders. RESULTS Women increased their weight and percent body fat by 1.7 +/- 4.7 kg and 2.1% +/- 3.9%, respectively, from during their first year of diagnosis to during their third year of diagnosis. A total of 68% and 74% of patients gained weight and body fat, respectively. Greater increases in weight were observed among women diagnosed with a higher disease stage, younger age, being postmenopausal, and women who decreased their physical activity from diagnosis to up to 3 years after diagnosis (P for trend < .05). CONCLUSION Weight and body fat increased in the postdiagnosis period. Future research should focus on the effect of physical activity on weight and fat loss and breast cancer prognosis.

Physical activity levels among breast cancer survivors

Implications for Muscle Lipid Metabolism and An accumulation of intramuscular lipid has been reported with obesity and linked with insulin resistance. The purpose of this paper is to discuss: 1) mechanisms that may be responsible for intramuscular lipid accumulation with obesity, and 2) the effects of common interventions (weight loss or exercise) for obesity on skeletal muscle lipid metabolism and intramuscular lipid content. Data suggest that the skeletal muscle of morbidly obese humans is characterized by the preferential partitioning of lipid toward storage rather than oxidation. This phenotype may, in part, contribute to increased lipid deposition in both muscle and adipose tissue, and promote the development of morbid obesity and insulin resistance. Weight loss intervention decreases intramuscular lipid content, which may contribute to improved insulin action. On the other hand, exercise training improves insulin action and increases fatty acid oxidation in the skeletal muscle of obese/morbidly obese individuals. In summary, the accumulation of intramuscular lipid appears to be detrimental in terms of inducing insulin resistance; however, the accumulation of lipid can be reversed with weight loss. The mechanism(s) by which exercise enhances insulin action remains to be determined.INTRODUCTION/PURPOSE The Talk Test has been shown to be well correlated with the ventilatory threshold, with accepted guidelines for exercise prescription, and with the ischemic threshold. As such, it appears to be a valuable although quite simple method of exercise prescription. In this study, we evaluate the consistency of the Talk Test by comparing responses during different modes of exercise. METHODS Healthy volunteers (N = 16) performed incremental exercise, on both treadmill and cycle ergometer. Trials were performed with respiratory gas exchange and while performing the Talk Test. Comparisons were made regarding the correspondence of the last positive, equivocal, and first negative stages of the Talk Test with ventilatory threshold. RESULTS The %VO2peak, %VO2 reserve, %HRpeak, and %HR reserve at ventilatory threshold on treadmill versus cycle ergometer (77%, 75%. 89%, and 84% vs 67%, 64%, 82%, and 74%) were not significantly different than the equivocal stage of the Talk Test (83%, 82%, 86%, and 80% vs 73%, 70%, 87%, and 81%). The VO2 at ventilatory threshold and the last positive, equivocal and negative stages of the Talk Test were well correlated during treadmill and cycle ergometer exercise. CONCLUSIONS The results support the hypothesis that the Talk Test approximates ventilatory threshold on both treadmill and cycle. At the point where speech first became difficult, exercise intensity was almost exactly equivalent to ventilatory threshold. When speech was not comfortable, exercise intensity was consistently above ventilatory threshold. These results suggest that the Talk Test may be a highly consistent method of exercise prescription.INTRODUCTION Obesity and weight gain are negative prognostic factors for breast cancer survival. Physical activity (PA) prevents weight gain and may decrease obesity. Little information exists on PA levels among cancer survivors. We assessed PA, including the proportion of breast cancer survivors engaging in recommended levels, by categories of adiposity, age, disease stage, and ethnicity in 806 women with stage 0-IIIA breast cancer participating in the Health, Eating, Activity, and Lifestyle Study. METHODS Black, non-Hispanic white, and Hispanic breast cancer survivors were recruited into the study through Surveillance Epidemiology End Results registries in New Mexico, Western Washington, and Los Angeles County, CA. Types of sports and household activities and their frequency and duration within the third yr after diagnosis were assessed during an in-person interview. RESULTS Thirty-two percent of breast cancer survivors participated in recommended levels of PA defined as 150 min x wk(-1) of moderate- to vigorous-intensity sports/recreational PA. When moderate-intensity household and gardening activities were included in the definition, 73% met the recommended level of PA. Fewer obese breast cancer survivors met the recommendation than overweight and lean breast cancer survivors (P < 0.05). Fewer black breast cancer survivors met the recommendation compared with non-Hispanic white and Hispanic breast cancer survivors (P < 0.05). CONCLUSIONS Most of the breast cancer survivors were not meeting the PA recommendations proposed for the general adult population. Efforts to encourage and facilitate PA among these women would be an important tool to decrease obesity, prevent postdiagnosis weight gain, and improve breast cancer prognosis.PURPOSE To derive a regression equation that estimates metabolic equivalent (MET) from accelerometer counts, and to define thresholds of accelerometer counts that can be used to delineate sedentary, light, moderate, and vigorous activity in adolescent girls. METHODS Seventy-four healthy 8th grade girls, age 13 - 14 yr, were recruited from urban areas of Baltimore, MD, Minneapolis/St. Paul, MN, and Columbia, SC, to participate in the study. Accelerometer and oxygen consumption (.-)VO(2)) data for 10 activities that varied in intensity from sedentary (e.g., TV watching) to vigorous (e.g., running) were collected. While performing these activities, the girls wore two accelerometers, a heart rate monitor and a Cosmed K4b2 portable metabolic unit for measurement of (.-)VO(2). A random-coefficients model was used to estimate the relationship between accelerometer counts and (.-)VO(2). Activity thresholds were defined by minimizing the false positive and false negative classifications. RESULTS The activities provided a wide range in (.-)VO(2) (3 - 36 mL x kg x min) with a correspondingly wide range in accelerometer counts (1- 3928 counts x 30 s). The regression line for MET score versus counts was MET = 2.01 +/- 0.00171 (counts x 30 s) (mixed model R = 0.84, SEE = 1.36). A threshold of 1500 counts x 30 s defined the lower end of the moderate intensity (approximately 4.6 METs) range of physical activity. That cutpoint distinguished between slow and brisk walking, and gave the lowest number of false positive and false negative classifications. The threshold ranges for sedentary, light, moderate, and vigorous physical activity were found to be 0 - 50, 51- 1499, 1500 - 2600, and >2600 counts x 30 s, respectively. CONCLUSION The developed equation and these activity thresholds can be used for prediction of MET score from accelerometer counts and participation in various intensities of physical activity in adolescent girls.

Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer

PURPOSE Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. PATIENTS AND METHODS We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. RESULTS Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer-specific or all-cause mortality. CONCLUSION Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.