Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men

BACKGROUND: Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass (FFM) and skeletal muscle and decreases in fat mass (FM) but have not reported the impact of baseline body composition. OBJECTIVE: The objective of the study was to determine the effect, in nonobese aging men with symptoms of androgen deficiency and low-normal serum testosterone levels, of testosterone therapy on total and regional body composition and hormonal and metabolic indices. METHODS: Sixty healthy but symptomatic, nonobese men aged 55 yr or older with total testosterone (TT) levels less than 15 nm were randomized to transdermal testosterone patches or placebo for 52 wk. Body composition, by dual-energy x-ray absorptiometry (FM, FFM, skeletal muscle) and magnetic resonance imaging (abdominal sc and visceral adipose tissue, thigh skeletal muscle, and intermuscular fat) and hormonal and metabolic parameters were measured at wk 0 and 52. RESULTS: Serum TT increased by 30% (P = 0.01), and LH decreased by 50% (P < 0.001). Relative to placebo, total body FFM (P = 0.03) and skeletal muscle (P = 0.008) were increased and thigh skeletal muscle loss was prevented (P = 0.045) with testosterone therapy and visceral fat accumulation decreased (P = 0.001) without change in total body or abdominal sc FM; change in visceral fat was correlated with change in TT levels (r2 = 0.36; P = 0.014). There was a trend to increasing total and low-density lipoprotein cholesterol with placebo. CONCLUSION: Testosterone therapy, relative to placebo, selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass. Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk.     

Serum total and bioavailable testosterone levels, central obesity, and muscle strength changes with aging in healthy Chinese men

OBJECTIVES: To investigate the effects of the changes in serum bioavailable and total testosterone (TT) levels with aging on visceral body fat distribution and muscle strength in Chinese men.
DESIGN: Cross-sectional study.
SETTING: Ambulatory care.
PARTICIPANTS: Four hundred seventy-five healthy ambulatory Chinese men (aged 18–89, body mass index (BMI) 16.4–40.0 kg/m²).
MEASUREMENTS: Morning serum total and bioavailable testosterone levels, waist circumference (WC), waist-hip ratio (WHR), and right handgrip strength.
RESULTS: Mean serum TT levels fell mildly but significantly with aging ( P =.02, linear trend; one-way analysis of variance (ANOVA)), whereas mean serum bioavailable testosterone (BT) levels fell greatly with aging ( P <.001, linear trend, one-way ANOVA). The rates of decline in serum TT and BT levels were 0.2% and 1.14% per year, respectively. [Correction added after online publication 14-May-2008: BT levels have been corrected from 1.44% to 1.14%.] After adjustment for adiposity according to BMI, multiple linear regression analyses showed that age remained significantly related to serum TT and BT levels. Handgrip strength decreased with age (correlation coefficient ( r )=−0.394, P <.001) and was greater with higher serum BT levels ( r =0.239, P <.001) but not with higher TT levels. WHR, before and after adjustment for BMI, was inversely related to serum TT ( r =−0.34 and −0.197 respectively, P <.001) and BT levels ( r =−0.104, P <.05 and −0.161, P <.001, respectively).
CONCLUSION: In Chinese men, serum BT levels decreased with aging and may contribute to central obesity and poorer muscle strength in aging men.     

Sit-to-Stand Kinetics and Correlates of Performance in Young and Older Males

PurposeTo compare sit-to-stand (STS) kinetics in young (YM) and older (OM) males and determine correlates of STS performance.MethodsYM (n = 15, age = 20.7 ± 2.2 yrs) and OM (n = 15, age = 71.6 ± 3.9 yrs) performed a single STS task as quickly as possible on a force plate and the vertical ground reaction force (VGRF) signal was analyzed. Peak VGRF, as well as peak (100 ms rolling average), early (minimum VGRF to 50% peak VGRF), late (50% peak VGRF to peak VGRF), and overall (minimum VGRF to peak VGRF) rate of force development (RFD) were calculated. Power (absolute and relative) and velocity parameters as well as rate of electromyography rise (RER) were also obtained.ResultsSTS time, average power, early RFD, and lower limb lean mass were similar between groups (p > 0.05). All other power, velocity, RFD, and RER measures were lower in OM (p < 0.05; d = 0.41-2.19). Peak VGRF and all RFD measures, except late RFD, were strongly correlated with STS performance in OM, while peak VGRF and peak RFD were only moderately correlated with performance in YM.ConclusionsMost kinetic variables, except absolute average power, were diminished in OM, and there was a preferential decrease in late RFD compared to early RFD. Peak VGRF and RFD exhibited stronger correlations with STS time and power in OM compared to YM, and early RFD appears to be more influential for STS performance than late RFD. These findings may be useful for practitioners/clinicians involved in designing interventions aimed at optimizing STS performance in older adults.     

Low testosterone levels and decline in physical performance and muscle strength in older men: findings from two prospective cohort studies

Objective Progressive declines in serum levels of testosterone parallel the decline in physical performance and muscle strength in ageing men, although findings are not conclusive. We examined whether levels of testosterone were associated with 3‐year decline in physical performance and muscle strength in older men. Design Longitudinal data were available for 486 men (mean age 74·9 years, SD 6·4) from the Longitudinal Ageing Study Amsterdam (LASA) and 1071 well‐functioning men (mean age 73·7 years, SD 2·8) from the Health, Ageing and Body Composition (Health ABC) study. Measurements Three‐year change in physical performance score and grip strength according to categories of total testosterone (TT) and free testosterone (FT) levels. Results The mean 3‐year change in physical performance was –1·1 (SD 2·7, –13·6%) in LASA and –0·3 (SD 1·5, –2·9%) in Health ABC. The mean 3‐year change in grip strength was –9·7 kg (SD 12·2, –13·2%) in LASA and –4·4 kg (SD 11·4,–5·8%) in Health ABC. Low levels of TT were not associated with decline in physical performance or with decline in muscle strength [e.g. mean change in physical performance –1·09 (SD 0·26) in the lowest quartile (Q1) and –0·88 (0·24) in the highest quartile (Q4) of total testosterone in LASA, and –0·26 (0·07) vs.–0·36 (0·11) in Health ABC]. Similar results were found for FT. Conclusions Low levels of TT and FT were neither associated with 3‐year decline in physical performance nor with 3‐year decline in muscle strength in two independent samples of older men.     

Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men

In the present cross-sectional study of 403 independently living elderly men, we tested the hypothesis that the decreases in bone mass, body composition, and muscle strength with age are related to the fall in circulating endogenous testosterone (T) and estrogen concentrations. We compared various measures of the level of bioactive androgen and estrogen to which tissues are exposed. After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (age, 73-94 yr) were randomly selected from a population-based sample. Total T (TT), free T (FT), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were determined by RIA. Levels of non-SHBG-bound T (non-SHBG-T), FT (calc-FT), the TT/SHBG ratio, non-SHBG-bound E2, and free E2 were calculated. Physical characteristics of aging included muscle strength measured using dynamometry, total body bone mineral density (BMD), hip BMD, and body composition, including lean mass and fat mass, measured by dual-energy x-ray absorptiometry. In this population of healthy elderly men, calc-FT, non-SHBG-T, E1, and E2 (total, free, and non-SHBG bound) decreased significantly with age. T (total and non-SHBG-T) was positively related with muscle strength and total body BMD (for non-SHBG-T, respectively, beta = 1.93 +/- 0.52, P < 0.001 and beta = 0.011 +/- 0.002, P < 0.001). An inverse association existed between T and fat mass (beta = -0.53 +/- 0.15, P < 0.001). Non-SHBG-T and calc-FT were more strongly related to muscle strength, BMD, and fat mass than TT and were also significantly related to hip BMD. E1 and E2 were both positively, independently associated with BMD (for E2, beta = 0.21 +/- 0.08, P < 0.01). Non-SHBG-bound E2 was slightly strongly related to BMD than total E2. The positive relation between T and BMD was independent of E2. E1 and E2 were not related with muscle strength or body composition. In summary, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging. A positive relation with muscle strength and BMD and a negative relation with fat mass was found. In addition, both serum E1 and E2 seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of the study precludes a definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD.     

Serum 25-hydroxyvitamin D concentration and physical function in adult men

Objective Recent reports suggest that vitamin D status influences musculoskeletal health; yet, there are limited data in adult men. This study investigated whether serum 25‐hydroxyvitamin D [25(OH)D] concentration was associated with lean body mass, muscle strength and physical performance in men. Design Population‐based, observational survey. Participants 1219 black, Hispanic and white randomly selected men aged 30–79 years from the Boston Area Community Health/Bone Survey. Measurements Lean body mass by dual‐energy X‐ray absorptiometry, hand grip strength, a composite physical function score (chair stand and walking speed), 25(OH)D, parathyroid hormone (PTH), testosterone, age, race, body mass index, socioeconomic status, education, smoking, arthritis, self‐reported health, calcium intake, physical activity. Results The distributions of serum 25(OH)D quartiles differed by race/ethnicity, education and smoking status. After adjustment for multiple lifestyle factors, serum 25(OH)D was not related to lean body mass, grip strength or the composite physical function score (all P > 0·20). There was no variation in the associations between 25(OH)D level and outcomes by race/ethnicity. The relationship between PTH and the outcomes revealed similar results. Conclusion In this population‐based sample of adult men with a broad age range, there was no association between serum 25(OH)D concentration and lean body mass, muscle strength and physical function after controlling for multiple lifestyle factors.     

Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal.

Postprandial testosterone concentrations have been shown to significantly decrease after a fat-rich meal, which may be due to inhibition of testosterone production by chylomicrons. We examined the effects of a high-fat diet known to reduce postprandial chylomicrons on the testosterone response to a fat-rich meal. Total testosterone (TT), free testosterone (FT), cortisol, and insulin responses to a high-fat test meal containing 5.44 MJ (1,300 kcal, 11% carbohydrate, 3% protein, 86% fat) were determined before (week 0) and after (week 8) an 8-week high-fat diet (64% fat) in 11 healthy men. The high-fat diet resulted in significant reductions in postabsorptive and postprandial serum triacylglycerols (55% and 50%, respectively). There were no significant changes in postabsorptive serum TT, FT, and cortisol, but insulin concentrations were significantly (P < or = .05) lower at week 8 (-28%). There was a significant reduction 1 hour after the fat-rich meal for TT (-22%) and FT (-23%), which remained significantly below baseline for 8 hours. Postprandial TT and FT responses were not significantly different after the 8-week high-fat diet. Postprandial serum cortisol concentrations were significantly reduced 1 hour after the meal. There were no significant differences before and after the high-fat diet. Insulin was significantly increased at the 0-, 1-, and 2-hour postprandial time points before and after the high-fat diet. Compared with week 0, insulin concentrations were significantly lower prior to and immediately after the fat-rich meal at week 8. These data indicate a fat-rich meal results in a prolonged reduction in TT and FT concentrations that is not altered by lowering postprandial chylomicrons. Alternative mechanisms (eg, higher uptake at the receptor level of cells) other than chylomicron-induced or insulin-induced inhibition of steroidogenesis are likely responsible for the reduction in TT and FT after a fat-rich meal.     

雄激素及其受体与老年男性冠状动脉粥样硬化性心脏病的相关性研究

目的 观察老年男性冠状动脉粥样硬化性心脏病(冠心病)患者性激素及雄激素受体水平的变化及相关性. 方法 横断面调查老年男性539例,其中健康人(对照组)400例,年龄62～92岁,平均(71.4±5.2)岁;冠心病患者139例,年龄60～88岁,平均(73.6±6.4)岁.测定总睾酮、游离睾酮、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇、黄体生成素(LH)、卵泡刺激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平. 结果 老年男性冠心病患者DHAES、总睾酮、SHBG、游离睾酮、AR荧光强度均低于对照组(均为P<0.01),而FSH、E2高于对照组(均为P<0.01).年龄与总睾酮、游离睾酮呈负相关(r分别为-0.28、-0.17,P<0.01和P<0.05);与E2、SHBG呈正相关(r分别为0.33、0.14,P<0.01和P<0.05).AR荧光强度与收缩压呈负相关(r=-0.12,P<0.01).Logistic回归分析显示,总睾酮(OR=1.065,95%CI:1.012～1.121,P<0.05)、SHBG(OR=0.994,95%CI:0.990～0.998,P<0.01)和AR(OR=0.971,95%CI:0.956～0.986,P<0.01)与老年男性冠心病相关. 结论 老年男性冠心病患者存在低水平的DHEAS、总睾酮、SHBG、游离睾酮、AR,同时存在高水平的FSH、E2;低水平总睾酮、SHBG和AR可能是老年男性冠心病独立的危险因素.     

Regulation of macronutrient balance in healthy young and older men.

OBJECTIVE: To determine the influence of age on the ability to adjust macronutrient oxidation to changes in diet composition. Our hypothesis was that the ability to adjust macronutrient oxidation to changes in diet composition would be impaired with age. DESIGN: Cross-sectional, randomized to three different isocaloric diets containing a constant percentage protein but varying in percentage fat and percentage carbohydrate: mixed diet (M; 15/30/55); high-fat diet (HF; 15/60/25), and high-carbohydrate (HC; 15/15/70). SUBJECTS: Six young (YM; age=25+/-1 y) and five middle-aged and older men (OM; age=63+/-3 y). MEASUREMENTS: Each subject underwent 24 h whole-room calorimetry on day 4 of each diet to determine 24 h macronutrient oxidation rates. Macronutrient balance was calculated from the individual macronutrient oxidation rates and the corresponding macronutrient intake. RESULTS: Body mass, percentage fat, and fat-free mass were similar in the two groups. Twenty-four-hour energy expenditure (EE) and energy balance did not differ across diets or between groups; 24 h EE was approximately 7% lower (NS) in the OM. Macronutrient oxidation rates were not significantly different in YM vs OM during M. Protein oxidation was similar across diets, but higher (P<0.05) in OM. Fat oxidation contributed 28.8+/-7.0% vs 37.8+/-4.7% to 24 h EE on M (NS) in the OM vs YM, respectively. This increased to 58.4+/-6.7 vs 51.9+/-5.3% of 24 h EE (NS) in the OM vs YM, respectively, during HF and decreased to 25.4+/-9.7 vs 20.2+/-14.3% (NS) during HC (diet effect, both P<0.05). Carbohydrate oxidation contributed 54.3+/-10.5% vs 56.6+/-2.4% of 24 h EE (NS) on M in the OM vs YM, respectively. This decreased to 19.5+/-10.6 vs 29.9+/-12.6% (NS) during HF and increased to 53.6+/-12.3 vs 64.7+/-14.3% (NS) in the OM vs YM, respectively during HC (diet effect, P<0.05). CONCLUSION: Taken together, these results suggest that the ability to adjust macronutrient oxidation to changes in diet composition is maintained in OM and, thus, is unlikely to contribute to the increased susceptibility to weight gain and obesity development that accompanies aging.     

Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age.

As men age, serum testosterone concentrations decrease, the percentage of body mass that is fat increases, the percentage of lean body mass decreases, and muscle strength decreases. Because these changes are similar to those that occur in hypogonadal men, we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass, increase their lean mass, and increase their muscle strength. We randomized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months. We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment. Ninety-six men completed the entire 36-month protocol. Fat mass decreased (-3.0+/-0.5 kg) in the testosterone-treated men during the 36 months of treatment, which was significantly different (P = 0.001) from the decrease (-0.7+/-0.5 kg) in the placebo-treated men. Lean mass increased (1.9+/-0.3 kg) in the testosterone-treated men, which was significantly different (P < 0.001) from that (0.2+/-0.2 kg) in the placebo-treated men. The decrease in fat mass in the testosterone-treated men was principally in the arms (-0.7+/-0.1 kg; P < 0.001 compared to the placebo group) and legs (-1.1+/-0.2 kg; P < 0.001), and the increase in lean mass was principally in the trunk (1.9+/-0.3 kg; P < 0.001). The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment, however, was not significantly different between the two groups. We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass, principally in the arms and legs, and increased lean mass, principally in the trunk, but did not increase the strength of knee extension and flexion, as measured by dynamometer.     

雄激素及其受体和雌激素变化在老年男性高血压患者中的初步研究

目的探讨老年男性高血压患者的雄激素及其受体以及雌激素水平变化。方法选择172例老年男性高血压患者(高血压组)和104例同龄健康男性(健康组),检测所有入选者血清7种性激素,黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(TT)和雌二醇(E2)采用化学发光法检测;游离睾酮(FT),硫酸脱氢表雄酮(DHEA-s),性激素结合球蛋白(SHBG)采用酶联免疫吸附法检测。使用流式细胞技术测定外周淋巴细胞的雄激素受体(AR)含量(AR平均荧光强度)。结果(1)与健康组比较,高血压组体重指数(BMI),腰围,腰臀比,空腹血糖和E2/TT明显增高,TT明显下降(P<0.01)(。2)控制BMI因素影响后,与收缩压相关的性激素有TT(P=0.047)和E2/TT(P=0.001);与舒张压相关的因素有E2,E2/TT和AR荧光强度(P<0.05)。结论男性高血压患者TT明显下降、E2/TT明显升高。E2/TT与收缩压和舒张压呈正相关,E2和AR荧光强度与舒张压呈正相关。     

Oestradiol is a protective factor for non-alcoholic fatty liver disease in healthy men

Visceral fat is a risk factor for non‐alcoholic fatty liver disease (NAFLD). A reduction in sex hormones is associated with increased abdominal fat. Thus, we investigated whether reduced testosterone (T) or oestradiol (E2) levels in men are associated with NAFLD and central obesity. The study involved a survey of 1,882 men between 20 and 60 years of age. We detected hepatic fat infiltration by ultrasound. Early morning serum was analyzed for total testosterone (TT), E2, sex hormone‐binding globulin (SHBG), follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Free testosterone (FT) was calculated using the Vermeulen method. In the studied population, the prevalence of NAFLD, FSH, LH and SHBG increased with age, TT and FT declined with age, and E2 remained stable. However, in the NAFLD group, TT remained stable, FT and E2 declined, and hepatic fat infiltration increased (P < 0.001 for both). Using multivariate analysis, a correlation was found between E2 and NAFLD, with an odds ratio of 0.954 (95% confidence interval: 0.946–0.967). E2 is one of the protective factors against NAFLD in healthy men. T has no significant correlation with NAFLD. Further investigation would be required to assess the clinical consequences of reduced E2 in men with NAFLD, particularly for men whose TT remained stable.     

性激素和雄激素受体与老年男性糖尿病的相关性研究

目的 研究老年男性糖尿病患者的性激素和雄激素受体水平的变化,探讨老年男性糖尿病患者性激素和雄激素受体与糖尿病的相关性. 方法横断面调查老年男性492例,其中健康对照组104例,平均年龄(71.4±5.2)岁;非糖尿病对照组259例,平均年龄(71.5±5.0)岁;糖尿病组129例,平均年龄(73.0±6.3)岁.测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E_2)、黄体生成素(LH)、卵泡刺激素(FSH)水平,采用流式细胞术检测外周血白细胞雄激素受体(AR)水平. 结果糖尿病组TT水平显著低于两对照组,分别为(17.1±6.1)、(15.8±6.0)nmol/L和(13.8±4.7)nmol/L(P<0.01),FT、SHBG、AR阳性率、AR荧光强度健康对照组、非糖尿病对照组和糖尿病组3组间呈下降趋势.但差异无统计学意义.多元回归分析町见TT、E_2,E_2/T,SHBG与血糖水平呈负相关;SHBG与糖尿病病程呈正相关.TT和AR阳性率与糖尿病病程呈负相关.Logistic多元同归分析示年龄、腰臀围比、FSH、SHBG、AR阳性率是糖尿病的危险因素. 结论低水平的TT、SHBG和AR可能是糖尿病的危险因素,在老年男性糖尿病的发生和发展中起到一定作用.     

Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction

OBJECTIVE: Androgens are essential in the maintenance of nitric oxide-mediated erectile activity in the rat. The objective of the present study was to investigate the role of androgens in regulating trabecular smooth muscle relaxation in the corpus cavernosum in response to vasoactive challenge in men with erectile dysfunction (ED). DESIGN: Retrospective, double-blind correlation analyses. PATIENTS: Fifty-two impotent patients without confounding risk factors for ED were obtained from a total of 250 undergoing diagnostic evaluation. MEASUREMENTS: All patients had dynamic colour duplex ultrasound (D-CDU) and hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol. RESULTS: Based upon D-CDU results patients were diagnosed as having arteriogenic (AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49) ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)-ED was made by comprehensive psychogenic testing and confirmed by normal D-CDU results. AR and CVO patients had altered compliance of cavernous arteries recorded by D-CDU [20-25% lower resistive index (RI) than patients with psychogenic ED], and lower free testosterone (FT) levels than psychogenic patients [42.3 +/-3.5 SE and 49.3+/-5.2 vs. 75.2+/-7.6 pmol/l, respectively; P<0.01]. More important, in all patients there was a strong direct correlation between resistive index values and FT levels (r = 0.47, P = 0.002); the relationship was maintained also when adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02). CONCLUSIONS: These results indicate that in men with erectile dysfunction low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.     

Obesity and testicular function

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.     

Serum albumin and muscle strength: a longitudinal study in older men and women

OBJECTIVES: To examine whether low serum albumin is associated with low muscle strength and future decline in muscle strength in community-dwelling older men and women. DESIGN: Population-based cohort study. SETTING: The Longitudinal Aging Study Amsterdam. PARTICIPANTS: Six hundred seventy-six women and 644 men aged 65 to 88. MEASUREMENTS: Serum albumin was determined at baseline. Muscle strength was assessed using grip strength at baseline, after 3 (n=1,009), and 6 (n=741) years. The outcomes were continuous baseline muscle strength, 3- and 6-year change in muscle strength, and a dichotomous indicator for substantial decline (a decrease if > or =1 standard deviations for women=11 kg, for men=12 kg) in muscle strength. RESULTS: Mean serum albumin concentration+/-standard deviation was 45.0+/-3.3 g/L for women and 45.2+/-3.2 g/L for men. At baseline, adjusting for age, lifestyle factors, and chronic conditions, lower serum albumin was cross-sectionally associated with weaker muscle strength (P<.001) in women and men. After 3 years of follow-up, mean decline in muscle strength was -5.6+/-10.9 kg in women and -9.6+/-11.9 kg in men. After adjustment for potential confounders, lower serum albumin was associated with muscle strength decline over 3 years (P<.01) in women and men (beta=0.57, standard error (SE)=0.18; beta=0.37, SE=0.16, respectively). Lower serum albumin was also associated with substantial decline in muscle strength in women (per unit albumin (g/L) adjusted odds ratio (OR)=1.14, one-sided 95% confidence limit (CL)=1.07) and men (per unit albumin (g/L) adjusted OR=1.14, 95% CL=1.08). Similar but slightly weaker associations were found between serum albumin and 6-year change in muscle strength (P<.05). CONCLUSION: These results suggest that low serum albumin, even within the normal range, is independently associated with weaker muscle strength and future decline in muscle strength in older women and men.     

Triceps surae muscle power, volume, and quality in older versus younger healthy men

This study investigated whether loss of power with aging is fully accounted for by a decrease in muscle volume. Triceps surae power and volume (VOL) were measured in 18 older (OM: 69-82 years) and 12 younger men (YM: 19-35 years). Isokinetic peak torque was measured to determine torque-velocity and power-velocity relationships. Both peak power observed (PP(obs)) and peak power estimated from Hill's equation (PP(est)) were markedly reduced in the OM (PP(obs) was 45% and PP(est) was 43% of those of the YM). VOL was 81% of that of the YM (p <.001). Specific power (PP(est)/VOL) of the OM was 55.2% of that of the YM (p <.001). Torque at PP(est) accounted for a greater proportion of the decline in PP(est) in the OM than did optimum velocity (50% vs 13%, respectively). Hence, the present results showed that only approximately half of the loss in triceps surae peak power in old age is due to decreases in muscle VOL.     

Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism

CONTEXT: There is a large interindividual variation in serum (free) testosterone (FT) levels in men, underlain in part by genetic components. OBJECTIVE: The objective of the study was to explore the hypothesis that this variability results in part from differences in androgen sensitivity and feedback loop set point and assess the role of the androgen receptor (AR) polyglutamine tract polymorphism encoded by a CAG repeat of variable length in exon 1 of the AR gene. DESIGN/SETTING/PARTICIPANTS: We performed a cross-sectional analysis in two independent populations of healthy men, consisting of 2322 men aged 35-59 yr (Belstress study) and 358 men aged 25-45 yr (Siblos study), respectively. MAIN OUTCOME MEASURES: Serum hormonal levels and the AR gene CAG repeat length were determined. RESULTS: In the Belstress population, serum testosterone and calculated FT showed a positive linear association with LH (P < 0.001). In the 200 men with lowest FT, CAG repeat number was lower than in the 200 men with highest FT (P = 0.004). As studied in a larger subset of the population consisting of 857 men covering the whole FT range, FT increased progressively with CAG repeat length (P = 0.003). These findings of a positive relation of FT with both LH and CAG repeat length were confirmed in the Siblos study population (both P < or = 0.001). Difference in FT between extreme quartiles of CAG repeat was 10 and 14% in the Belstress and Siblos study, respectively. In both study populations, CAG repeat length was also positively associated with serum total testosterone (P < or = 0.004). CONCLUSIONS: The data support the view that between-subject variability in serum FT in healthy men is underlain in part by differences in androgen sensitivity and feedback set point, with a contributory role of AR polymorphism. These findings have potential implications for the interpretation of epidemiological studies, diagnosis of hypogonadism, and pharmacogenetics of androgen treatment in men.