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The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women
Abstract
The objective of this study was to examine whether low levels of oestradiol and testosterone are associated with impaired mobility, low muscle strength and the incidence of falls in a population-based sample of older men and women.
Cross-sectional population-based study, based on data of the Longitudinal Ageing Study Amsterdam (LASA), including 623 men and 663 women, aged 65-88 years.
Serum levels of oestradiol, testosterone, albumin and sex hormone-binding globulin (SHBG) were measured. Physical performance, functional limitations and muscle strength were assessed, and a follow-up on falls was performed prospectively within 3 years.
After adjustment for age, level of education, alcohol use, physical activity, chronic disease and body mass index (BMI), men in the highest quartile of the oestradiol/SHBG ratio had significantly higher physical performance scores than men in the lowest quartile (beta = 0.103). Serum levels of total testosterone were positively associated with muscle strength (beta = 0.085). Calculated bioavailable testosterone levels were positively associated with physical performance and muscle strength (beta = 0.128 and 0.109 respectively). No associations of oestradiol levels with mobility were seen in women. Levels of oestradiol and testosterone were not associated with falls.
It can be concluded that low levels of sex hormones were associated with impaired mobility and low muscle strength in men, but not in women. Levels of sex hormones were not associated with the incidence of falls neither in men, nor in women.
... Frailty is recognized as a state of decreased reserve and diminished resilience to stressors among middle-and older-aged people, resulting from an accumulated decline in multiple physiological systems [1]. Although previous studies have recognized the relevance of identifying frailty in the population, no classification exists under the International Classification of Diseases [2]. ...
... Oestradiol (pmol/L) Endocrine system Declined oestradiol is associated with grip strength which is one of the indicators of frailty [1]. ...
... Nonetheless, our results should be interpreted with caution since they are not exempt from limitations. Firstly, our sample was a relatively young population compared to previous studies recruiting participants aged over 65 years [1,16]. Secondly, due to the non-probability sample from the UK Biobank study, our study reported a lower prevalence of frailty (4.8%) than the UK average (7.8%) [3]. ...
Objective:
This study aimed to compare the biomarker profile of pre-frail and frail adults in the UK Biobank cohort by sex.
Methods:
In total, 202,537 participants (67.8% women, aged 37 to 73 years) were included in this cross-sectional analysis. Further, 31 biomarkers were investigated in this study. Frailty was defined using a modified version of the Frailty Phenotype. Multiple linear regression analyses were performed to explore the biomarker profile of pre-frail and frail individuals categorized by sex.
Results:
Lower concentrations of apoA1, total, LDL, and HDL cholesterol, albumin, eGFRcys, vitamin D, total bilirubin, apoB, and testosterone (differences ranged from -0.30 to -0.02 per 1-SD change), as well as higher concentrations of triglycerides, GGT, cystatin C, CRP, ALP, and phosphate (differences ranged from 0.01 to 0.53 per 1-SD change), were identified both in pre-frail and frail men and women. However, some of the associations differed by sex. For instance, higher rheumatoid factor and urate concentrations were identified in pre-frail and frail women, while lower calcium, total protein, and IGF-1 concentrations were identified in pre-frail women and frail women and men. When the analyses were further adjusted for CRP, similar results were found.
Conclusions:
Several biomarkers were linked to pre-frailty and frailty. Nonetheless, some of the associations differed by sex. Our findings contribute to a broader understanding of the pathophysiology of frailty as currently defined.
... Cross-sectional associations between endogenous estrogens and progestogens and skeletal muscle size and function When compared to androgens, the effect of estrogens and progestogens on female skeletal muscle has been the focus of a large number of studies. A number of cross-sectional studies conducted on post-menopausal and elderly females (Baumgartner, Waters, Gallagher, Morley, & Garry, 1999;Rolland, Perry, Patrick, Banks, & Morley, 2007;Schaap et al., 2005;Sipilä et al., 2006;van Geel et al., 2009) aimed to investigate the role of endogenous estrogens in relation to sarcopenia and prevention of falls. These studies can be used to extract insights on the association between endogenous estrogens and skeletal muscle size and function. ...
... These studies can be used to extract insights on the association between endogenous estrogens and skeletal muscle size and function. Of these studies, three (n = 663 (Schaap et al., 2005), 180 (Baumgartner et al., 1999) and 175 (Grundberg et al., 2005)) found no association between estrogens (E1, E2) or genetic variations of ERα and ERβ, and muscle strength or muscle mass. One study found a positive association between E2 and muscle strength (n = 187) (Sipilä et al., 2006), and another study found a positive association between the E2/SHBG ratio and lean muscle mass but not strength (n = 329) (van Geel et al., 2009). ...
... The authors reported that, as is the case with testosterone, intramuscular E2 concentration was higher in post-than in pre-menopausal females (Pöllänen et al., 2011). E2 is thought to be produced predominantly in adipose tissue after menopause (Schaap et al., 2005), and therefore, the higher amounts of fat infiltrated within and between muscle cells may contribute to local steroidogenesis in post-menopausal females. In addition, the investigators made the intriguing suggestion that not only adipose cells, but also myogenic cells may be able to not only produce the ERs (Ekenros et al., 2017;Pöllänen et al., 2011) but also E2 itself in vitro (Pöllänen et al., 2015). ...
Sex steroids, commonly referred to as sex hormones, are integral to the development and maintenance of the human reproductive system. In addition, male (androgens) and female (estrogens and progestogens) sex hormones promote the development of secondary sex characteristics by targeting a range of other tissues, including skeletal muscle. The role of androgens on skeletal muscle mass, function and metabolism has been well described in males, yet female specific studies are scarce in the literature. This narrative review summarises the available evidence around the mechanistic role of androgens, estrogens and progestogens in female skeletal muscle. An analysis of the literature indicates that sex steroids play important roles in the regulation of female skeletal muscle mass and function. The free fractions of testosterone and progesterone in serum were consistently associated with the regulation of muscle mass, while estrogens may be primarily involved in mediating the muscle contractile function in conjunction with other sex hormones. Muscle strength was however not directly associated with any hormone in isolation when at physiological concentrations. Importantly, recent evidence suggests that intramuscular sex hormone concentrations may be more strongly associated with muscle size and function than circulating forms, providing interesting opportunities for future research. By combining cross-sectional, interventional and mechanical studies, this review aims to provide a broad, multidisciplinary picture of the current knowledge of the effects of sex steroids on skeletal muscle in females, with a focus on the regulation of muscle size and function and an insight into their clinical implications.
• Highlights
• Free testosterone, but not total testosterone, is associated with lean mass but not strength in pre- and post-menopausal females.
• Progesterone and estrogens may regulate muscle mass and strength, respectively, in females.
• Intra-muscular steroids may be more closely associated to muscle mass and strength, compared to systemic fractions.
... 27,[30][31][32] Consequently, low testosterone levels are associated with functional impairment, increased risk of falls, and decreased quality of life. 33 Testosterone is known to reduce with age in both sexes, but most studies have focused on males, and the benefit of androgenic hormones in females remains largely unresolved. 33 A meta-analysis by Correa et al. revealed that androgen replacement therapy (ART) is associated with increased muscle mass and strength in addition to physical performance in middle-aged/ older males. ...
... 33 Testosterone is known to reduce with age in both sexes, but most studies have focused on males, and the benefit of androgenic hormones in females remains largely unresolved. 33 A meta-analysis by Correa et al. revealed that androgen replacement therapy (ART) is associated with increased muscle mass and strength in addition to physical performance in middle-aged/ older males. 36 However, ART is associated with potential side effects, such as prostatic hypertrophy and cardiovascular events. ...
Background
Sarcopenia is an age‐related condition characterized by a progressive and systemic decline in skeletal muscle mass, quality, and strength. The incidence of sarcopenia contains sex‐specific aspects, indicating the contribution of sex hormones to its pathophysiology. This review focuses on changing trends in sarcopenia, discusses alterations in definitions and diagnostic criteria, and emphasizes the association between sarcopenia and sex hormones.
Methods
A literature search was performed on PubMed for related articles published between 1997 and December 2023 using appropriate keywords.
Main Findings (Results)
Advances in research have emphasized the significance of muscle quality and strength over muscle mass, resulting in new diagnostic criteria for sarcopenia. Androgens demonstrated anabolic effects on skeletal muscles and played a significant role in the pathophysiology of sarcopenia. In clinical settings, androgen replacement therapy has exhibited certain positive outcomes for treating sarcopenia, despite concerns about potential side effects. Conversely, estrogen is involved in skeletal muscle maintenance, but the detailed mechanisms remain unclear. Moreover, results regarding the clinical application of estrogen replacement therapy for treating sarcopenia remained inconsistent.
Conclusion
The elucidation of molecular mechanisms that involve sex hormones is eagerly awaited for novel therapeutic interventions for sarcopenia.
... Numerous cross-sectional studies have confirmed significant correlations between testosterone and frailty in men [52][53][54]. A Massachusetts cohort study that included 646 men aged 50-86 years investigated the relationship between testosterone and frailty and its components [52]. ...
... and 1.6 (95% CI 1.0-2.5) in TT and FT, respectively) [53]. Another cross-sectional study based on data from the Longitudinal Aging Study Amsterdam (LASA) that included 623 men also suggested a potential correlation between low TT or bioavailable testosterone levels and impaired mobility and low muscle strength in men [54]. In a study of 461 individuals aged 60 years and older, a low FT value (<243 pmol/L) was a significant risk factor for developing frailty [55]. ...
Age-related decline in testosterone is known to be associated with various clinical symptoms among older men and it is possible that the accompanying decline in muscle mass and strength might lead to a decline in motor and physical functions. Sarcopenia is an important pathophysiological factor associated with frailty in older adults and is diagnosed in older adults as a decrease in muscle strength, muscle mass, and walking speed, which can lead to a significant decline in the quality of life and shortened healthy life expectancy. Testosterone directly interacts with the androgen receptor expressed in myonuclei and satellite cells and is also indirectly associated with muscle metabolism through various cytokines and molecules. Currently, significant correlations between testosterone and frailty in men have been confirmed by numerous cross-sectional studies. Many randomized control studies have also supported the beneficial effect of testosterone replacement therapy (TRT) on muscle volume and strength among men with low to normal testosterone levels. In the world’s aging society, TRT can be a tool for preventing the onset of sarcopenia in older-adult men. This narrative review aims to show the relationship between the decline in testosterone with age, sarcopenia, and frailty, as well as the effects of testosterone replacement therapy on muscle mass and strength.
... Testosterone levels are associated with muscle strength and physical performance in healthy men [76]. This meta-analysis found no significant changes in testosterone and free testoster- one levels after the exercise interventions (see Table 4), perhaps due to differences in the test- ing methods, the number of included studies and, more importantly, because this secondary outcome was extracted from studies mainly reporting changes in muscle strength. ...
... High levels of IL-6 are related to T-cell failure [77], a greater risk of losing 40% of muscle strength [76] in the aging population, and a 1.3 times higher chance of presenting with a CVD [78]. Thus, strategies directed towards controlling levels of IL-6 may be helpful in PLWH. ...
Infection with human immunodeficiency virus (HIV) affects muscle mass, altering independent activities of people living with HIV (PLWH). Resistance training alone (RT) or combined with aerobic exercise (AE) is linked to improved muscle mass and strength maintenance in PLWH. These exercise benefits have been the focus of different meta-analyses, although only a limited number of studies have been identified up to the year 2013/4. An up-to-date systematic review and meta-analysis concerning the effect of RT alone or combined with AE on strength parameters and hormones is of high value, since more and recent studies dealing with these types of exercise in PLWH have been published.Randomized controlled trials evaluating the effects of RT alone, AE alone or the combination of both (AERT) on PLWH was performed through five web-databases up to December 2017. Risk of bias and study quality was attained using the PEDro scale. Weighted mean difference (WMD) from baseline to post-intervention changes was calculated. The I2 statistics for heterogeneity was calculated.Thirteen studies reported strength outcomes. Eight studies presented a low risk of bias. The overall change in upper body strength was 19.3 Kg (95% CI: 9.8-28.8, p< 0.001) after AERT and 17.5 Kg (95% CI: 16-19.1, p< 0.001) for RT. Lower body change was 29.4 Kg (95% CI: 18.1-40.8, p< 0.001) after RT and 10.2 Kg (95% CI: 6.7-13.8, p< 0.001) for AERT. Changes were higher after controlling for the risk of bias in upper and lower body strength and for supervised exercise in lower body strength. A significant change towards lower levels of IL-6 was found (-2.4 ng/dl (95% CI: -2.6, -2.1, p< 0.001).Both resistance training alone and combined with aerobic exercise showed a positive change when studies with low risk of bias and professional supervision were analyzed, improving upper and, more critically, lower body muscle strength. Also, this study found that exercise had a lowering effect on IL-6 levels in PLWH.
... Living rooms, bedrooms and kitchens were the most frequent sites for indoor falls, and women were particularly prone to falls in the kitchen and while engaging in housework [35,36]. In addition, as the ovarian function of older women diminishes after menopause, the secretion of estrogen decreases [37], causing an imbalance in bone metabolism and greater bone loss [38], thus making them more prone to osteoporosis. Furthermore, with age, their bone density decreases and their muscle strength and body functions weaken, increasing their chances of falls and fractures [39]. ...
Physical inactivity and sarcopenia are potentially modifiable risk factors for falls in older adults, but the strength of the association between physical activity (PA), sarcopenia, and falls in Chinese older adults is unclear. This study sought to investigate the potential mediation mechanism relationship in the connection between PA, sarcopenia, including its elements (muscle strength, physical performance, and skeletal muscle mass), and falls among Chinese older people. The subjects were 3592 community-dwelling Chinese aged 60 or over, selected from the China Health and Retirement Longitudinal Study (CHARLS). PA was evaluated through the International Physical Activity Questionnaire (IPAQ), and sarcopenia was determined through the Asian Working Group on Sarcopenia (AWGS) 2019 guidelines. We employed logistic regression to explore the link between physical activity, sarcopenia, and falls. Additionally, we applied Karlson, Holm and Breen’s (KHB) method to estimate two different mediation models. The results demonstrated that PA lowers the risk of falls [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.48–0.61], whereas sarcopenia increases the risk of falls (OR 1.34, 95% CI 1.16–1.55). Sarcopenia mediated the association between PA and falls, explaining a total of 2.69% of the association (indirect effect = −0.02). PA also had a significant mediating effect on the association between sarcopenia and falls, explaining a total of 20.12% of the association (indirect effect = 0.06). The proportion mediated by sarcopenia was 2.69% for PA and falls (indirect effect = −0.02). Our findings suggest that PA and sarcopenia have a direct effect on falls as well as an indirect effect through each other. Enhancing PA levels and preventing sarcopenia may help prevent falls in older adults.
... This is unusual given that testosterone improved muscle mass in previous studies, albeit not in the IBM setting [11][12][13]17]. Another study of older adults determined that testosterone concentrations are not associated with falls, therefore the falls that occurred are most likely to have been due to the underlying disease, and not related to testosterone [44]. It is also possible that testosterone supplementation increased levels of confidence, which may have led to increased activity and falls during this arm. ...
Introduction:
Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone.
Methods:
This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months.
Results:
14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events.
Conclusions:
Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.
... Ageing is associated with physiologic disturbance in glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), which have a role in maintaining β-cells growth and proliferation, contributing to β-cells dysfunction [43,44]. Reduced sex hormone secretion with ageing results in a reduction of lean muscle mass, increased visceral fat, reduction of subcutaneous fat and weight gain, which is another contributing factor to increased insulin resistance with ageing [45][46][47][48]. This age-related muscle-fat distribution leads to a reduction in the secretion of the beneficial myokines by the muscle cells and increased secretion of the harmful adipokines by the fat cells, resulting in an imbalance that promotes an unfavourable metabolic state such as increased insulin resistance, oxidative stress, low-grade inflammation, mitochondrial dysfunction and risk of diabetes [49,50]. ...
Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio–renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration.
... On the other hand, men are known to have higher grip strength than women across the lifespan, 47,48 possibly due to intrinsically higher levels of male hormones and stronger muscle strength. 49 In addition to intrinsic biological mechanisms, some sex-specific social factors might also be involved. For example, lifetime occupation has been found to be associated with both grip strength and cognitive function in older adults, 15 ...
Introduction:
This study investigated whether grip strength and gait speed predict cognitive aging trajectories and examined potential sex-specific associations.
Methods:
Community-dwelling older adults (n = 19,114) were followed for up to 7 years, with regular assessment of global function, episodic memory, psychomotor speed, and executive function. Group-based multi-trajectory modeling identified joint cognitive trajectories. Multinomial logistic regression examined the association of grip strength and gait speed at baseline with cognitive trajectories.
Results:
High performers (14.3%, n = 2298) and low performers (4.0%, n = 642) were compared to the average performers (21.8%, n = 3492). Grip strength and gait speed were positively associated with high performance and negatively with low performance (P-values < 0.01). The association between grip strength and high performance was stronger in women (interaction P < 0.001), while gait speed was a stronger predictor of low performance in men (interaction P < 0.05).
Discussion:
Grip strength and gait speed are associated with cognitive trajectories in older age, but with sex differences.
Highlights:
There is inter-individual variability in late-life cognitive trajectories.Grip strength and gait speed predicted cognitive trajectories in older age.However, sex-specific associations were identified.In women, grip strength strongly predicted high, compared to average, trajectory.In men, gait speed was a stronger predictor of low cognitive performance trajectory.
... Sarcopenic obesity is defined as the combination of obesity with low muscle mass and strength [35]. Although it can be caused by age-related changes in body composition [37], several pathways have also been proposed, including a sedentary lifestyle with less physically activity [38], higher inflammation status [39], insulin resistance [40], lower growth hormone and testosterone levels [41,42], relative malnutrition [43], and poor psychological status [44], all of which occur in older patients. ...
Background
Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) according to KDIGO category in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD according to KDIGO 2012 categories.
Methods
This is a cross-sectional study. The exposure variables (IC score and body mass index) and outcome variable (KDIGO categories of the risk of CKD) were collected at the same timepoint. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and KDIGO categories of risk of CKD.
Results
The KDIGO CKD risk category increased in parallel with IC score (p for trend < 0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a KDIGO moderately increased to very high risk category of CKD was 1.76 (1.31–2.37) times higher for those with an IC score of 2–5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the KDIGO moderately increased to very high risk category of CKD (synergy index = 1.683; 95% CI 0.630–3.628), and the proportion of the KDIGO moderately increased to very high risk category of CKD caused by this interaction was 25.6% (attributable proportion of interaction = 0.256).
Conclusions
Our findings indicate that IC score may be closely related to the KDIGO moderately increased to very high risk category of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the KDIGO CKD risk stage.
... However, functional muscle capacity remains of interest and is also used in the diagnosis of frailty. In general, most [136,158,183,185,[199][200][201] but not all [156,202] cross-sectional studies have shown positive associations between T levels and muscle strength. However, these studies were almost exclusively performed in older men. ...
... Sarcopenic obesity is de ned as the combination of obesity with low muscle mass and strength [35]. Although it can be caused by age-related changes in body composition [37], several pathways have also been proposed, including a sedentary lifestyle with less physically activity [38], higher in ammation status [39], insulin resistance [40], lower growth hormone and testosterone levels [41,42], relative malnutrition [43], and poor psychological status [44], all of which occur in older patients. ...
Background: Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD.
Methods: This is a cross-sectional study. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and CKD risk.
Results: The risk of CKD increased in parallel with IC score (p for trend<0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a moderately increased and very high risk stage of CKD was 1.76 (1.31-2.37) times higher for those with an IC score of 2-5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the risk of CKD (synergy index=1.683; 95% CI: 0.630-3.628), and the proportion of the CKD risk caused by this interaction was 25.6% (attributable proportion of interaction=0.256).
Conclusions: Our findings indicate that IC score may be closely related to the risk of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the risk of CKD.
... Those individuals with testosterone levels lower than the 25% quartile reference values exhibited a 40% increase in the risk of falls (Orwoll et al., 2006). In addition, cross-sectional population-based studies have shown that low testosterone levels were associated with decreased muscle strength, poor mobility, decreased muscle mass, and increased risk of falls (Schaap et al., 2005;Chiu et al., 2020). Furthermore, a pronounced testosterone decrease in aging men is associated with high mortality when compared to a normal decline in this hormone in age-matched individuals (Holmboe et al., 2018). ...
Sarcopenia is an emerging clinical condition determined by the reduction in physical function and muscle mass, being a health concern since it impairs quality of life and survival. Exercise training is a well-known approach to improve physical capacities and body composition, hence managing sarcopenia progression and worsening. However, it may be an ineffective treatment for many elderly with exercise-intolerant conditions. Thus, the use of anabolic-androgenic steroids (AAS) may be a plausible strategy, since these drugs can increase physical function and muscle mass. The decision to initiate AAS treatment should be guided by an evidence-based patient-centric perspective, once the balance between risks and benefits may change depending on the clinical condition coexisting with sarcopenia. This mini-review points out a critical appraisal of evidence and limitation of exercise training and AAS to treat sarcopenia.
... Accordingly, it is recommended to maintain a healthy WC. A possible explanation for this phenomenon is that excessive adiposity can downregulate the anabolic actions of testosterone (25), growth hormones (26), and insulin (27), which can contribute to a progressive loss of muscle mass and its functionality in both sexes. Additionally, excessive adipose tissue can induce a pro-inflammatory state by the action of several cytokines (e.g., higher plasma concentrations of tumor necrosis factor-alpha and interleukin-6), which is associated with lower muscle strength (28). ...
Handgrip strength (HGS) is a well-established indicator of muscle strength and a reasonable clinical predictor of metabolic health and diseases. This study explores the association between relative muscular strength and abdominal obesity (AO) in healthy Chilean adults. A convenience sample was recruited (n = 976) between 2018 and 2020. The HGS was determined by dynamometry. The anthropometry (weight, height, waist, and mid-arm circumference) and physical activity were also measured. The relative HGS (RHGS) was calculated by dividing the maximum HGS of the dominant hand by the body mass index. The AO was defined as a waist circumference (WC) >88 cm for women, and >102 cm for men. From the sample, 52.6% were women, 56.4% had excessive weight, and 42.7% had AO. The absolute and RHGS were greater in men compared to women (p < 0.001) and were decreased with age in both sexes. We observed a moderate negative correlation between WC and RHGS (rho = −0.54, and rho = −0.53, for men and women, respectively). The RHGS was lower in individuals with AO, independent of age and sex (p < 0.05). For each cm increase in WC, the odds of low RHGS (<25th percentile) increased by 12 and 9% for men and women, respectively. The AO is related to higher odds for low RHGS (OR: 1.72; 95% CI: 1.23–2.41). In our sample of healthy adults, a higher AO was associated with a lower muscle strength measured by dynamometry.
... 26,27 Older people are more likely to be frail because of reduced physical and physiological function, 6 and this issue is particularly significant in women with relatively low muscle mass after menopause. 28 Because the present study assessed falls in the workplace, the conditions and environment may be different from those in individuals' private lives, such as in the home. 29 Specifically, the current findings suggest that older people and women in agriculture may tend to be assigned light duties through work accommodation. ...
Objectives:
As the workforce ages, the incidence of occupational falls is increasing. However, risk factors for occupational falls in farm workers have not been evaluated in detail. The current study sought to identify the risk factors for occupational falls among middle-aged and elderly farm workers in Thailand.
Methods:
We conducted a cross-sectional study using a self-administered questionnaire among 419 farm workers aged ≥40 years in Nan province, Thailand. Multiple logistic regression analysis was used to examine the factors associated with occupational falls.
Results:
Occupational falls were experienced by 25.5% of participants. Men had 2.22 times higher odds of occupational falls than women (95% confidence interval [CI]: 1.19-4.13). Participants aged ≥60 years were less likely to experience occupational falls compared with those aged 40-49 years (odds ratio [OR]: 0.44; 95% CI: 0.20-0.96). Fruit growers were 2.72 times more likely to experience occupational falls than rice growers (95% CI: 1.33-5.55). Individuals with body mass index ≥30 kg/m2 and over were 3.05 times more likely to experience occupational falls than those with body mass index <25 kg/m2 (95% CI: 0.20-0.96).
Conclusion:
The sex- and age-related trends in fall risk may indicate that elderly individuals and women in agriculture tend to be assigned lighter duties through work accommodation. To prevent falls during agricultural work, it is necessary to pay attention to farm-specific tasks and work environments, such as working at a height in fruit cultivation, as well as instability of walking caused by obesity.
... Moreover, several studies in adult men have reported that the positive relationship between serum T and muscle strength could be nonlinear. In the Longitudinal Ageing Study Amsterdam, Schaap et al. found that only the concentration of total T (TT) in the 4th quartile group was related to muscle strength in 623 men [19]. The concentrations of sex hormones are among the factors that differ most prominently between the different stages of puberty. ...
This study analysed the associations of sex steroids with fat-free mass (FFM) and handgrip strength in 641 Chinese boys. Serum total testosterone (TT) and oestradiol were measured by chemiluminescence immunoassay. Free testosterone (FT) and oestradiol were calculated. FFM and handgrip strength were measured by bioelectrical impedance analysis and a hand dynamometer, respectively. Generalised additive models and multiple linear regression were used to explore the relationships. A subgroup analysis was conducted in early-mid pubertal and late-post pubertal groups. Age, height, weight, physical activity, intake of dietary protein and/or stage of puberty were adjusted. TT and FT were positively related to FFM and handgrip strength, with a curvilinear relationship being detected for handgrip strength ( p <0.050). This curvilinear relationship was only observed in the late-post pubertal group, suggesting a potential threshold effect (FT>11.99ng/dL, β = 1.275, p = 0.039). In the early-mid pubertal group, TT and/or FT were linearly or near-linearly related to FFM or handgrip strength (β = 0.003–0.271, p <0.050). The association between FT and FFM was stronger than that in the late-post pubertal group. This study found that serum T had different associations with muscle parameters in Chinese early-mid pubertal and late-post pubertal boys. In the late-post pubertal boys, serum T was curvilinearly related to muscle strength with a threshold effect and its link with muscle mass was weaker.
... Primary hypogonadism is caused by disruption at the level of the testis whilst secondary form is due to disruption at the level of the hypothalamus and pituitary. A decline in testosterone level in older men is associated with impaired mobility, lower muscle strength, and a decrease in muscle mass [3,4]. Testosterone replacement therapy (TRT) has been shown to have benefits on sexual function, mood and depressive symptoms, physical performance, and an increase in lean body mass [5][6][7]. ...
Testosterone replacement therapy (TRT) has become increasingly popular over the years and there has been an increasing debate on whether testosterone replacement should be offered to older men due to its association with cardiovascular events. In this study, we evaluated the risk of myocardial infarction (MI) associated with TRT in hypogonadal men through a meta-analysis. We carried out the analysis by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: Google Scholar, PubMed, Science Direct, Cochrane Library trials, and ClinicalTrials.gov. The search strategy resulted in a total of 782 articles, after applying our inclusion and exclusion criteria. Six observational studies and two randomized controlled trials (RCTs) were included for the analysis. A total of 55,806 hypogonadal men with baseline testosterone levels <300ng/mL were included in the analysis. The intervention group received testosterone in various routes including transdermal patches, gels, mouth patches, testosterone injections, and deposits. The incidence of MI was taken to be the primary measure outcomes. The pooled data from eight studies showed MI incidence in 249 out of 11,720 (2.1%) in the TRT group and 1420 out of 33,086 (4.3%) in the control group. The pooled OD showed no statistically significant association of TRT and MI compared to the control group (OR = 0.76, 95% CI 0.36-1.31; p=0.48). The model revealed high heterogeneity with I2 =79%. With sensitivity analysis and, excluding two studies out of the eight, the pooled data was able to achieve low heterogeneity with I2 = 0%. The newly pooled data from six studies showed MI incidence in 226 out of 10,137 (2.2%) in the TRT group and 969 out of 36,304 (2.7%) in the control group. The pooled OD shows no statistical significance in the association between TRT treatment and MI compared to the control group. (OR =0.87, 95% CI 0.75-1.01; P =0.08). It appears that TRT does not increase the risk of MI as compared to the non-intervention group. Further RCTs with greater population size are needed that could produce more solid results, allowing more definitive conclusions to be made on this topic.
... This may imply that there is a remaining biological difference and/or that other contributing determinants are missing from the current study, such as gender or dietary habits. Although beyond the scope of this study, other potential biological determinants have been proposed to account for sex differences in physical performance, such as sex hormones [29], body composition [17,30] and physiological differences in muscle function and structure [30]. These may explain the unexplained part of the sex difference in gait speed in the current study and could also explain the contributing role of some variables in our model like chronic diseases. ...
Background
This study explores whether a sex difference in sensitivity to (strength of the association) and/or in exposure to (prevalence) determinants of gait speed contributes to the observed lower gait speed among older women compared to men.
Methods
Data from the Longitudinal Aging Study Amsterdam (LASA) were used. In total 2407 men and women aged 55–81 years were included, with baseline measurements in 1992/2002 and follow-up measurements every 3–4 years for 15/25 years. Multivariable mixed model analysis was used to investigate sex differences in sensitivity (interaction term with sex) and in exposure to (change of the sex difference when adjusted) socio-demographic, lifestyle, social and health determinants of gait speed.
Results
Women had a 0.054 m/s (95 % CI: 0.076 − 0.033, adjusted for height and age) lower mean gait speed compared to men. In general, men and women had similar determinants of gait speed. However, higher BMI and lower physical activity were more strongly associated with lower gait speed in women compared to men (i.e. higher sensitivity). More often having a lower educational level, living alone and having more chronic diseases, pain and depressive symptoms among women compared to men also contributed to observed lower gait speed in women (i.e. higher exposure). In contrast, men more often being a smoker, having a lower physical activity and a smaller personal network size compared to women contributed to a lower gait speed among men (i.e. higher exposure).
Conclusions
Both a higher sensitivity and higher exposure to determinants of gait speed among women compared to men contributes to the observed lower gait speed among older women. The identified (modifiable) contributing factors should be taken into account when developing prevention and/or treatment strategies aimed to enhance healthy physical aging. This might require a sex-specific approach in both research and clinical practice, which is currently often lacking.
... The gradual decline in estradiol production in women and testosterone in men beginning near middle age is associated with the onset of muscle weakness. This relationship has been demonstrated clinically as hormone replacement therapy in both men and women is associated with improved muscle strength and function [117]. Overall, these findings support the hypothesis that sex-specific levels of sex hormones affect the incidence of CVD and muscle weakness throughout the lifespan. ...
Doxorubicin (DOX) is an anthracycline antibiotic used to treat a wide variety of hematological and solid tumor cancers. While DOX is highly effective at reducing tumor burden, its clinical use is limited by the development of adverse effects to both cardiac and skeletal muscle. The detrimental effects of DOX to muscle tissue are associated with the increased incidence of heart failure, dyspnea, exercise intolerance, and reduced quality of life, which have been reported in both patients actively receiving chemotherapy and cancer survivors. A variety of factors elevate the probability of DOX-related morbidity in patients; however, the role of sex as a biological variable to calculate patient risk remains unclear. Uncertainty regarding sexual dimorphism in the presentation of DOX myotoxicity stems from inadequate study design to address this issue. Currently, the majority of clinical data on DOX myotoxicity come from studies where the ratio of males to females is unbalanced, one sex is omitted, and/or the patient cohort include a broad age range. Furthermore, lack of consensus on standard outcome measures, difficulties in long-term evaluation of patient outcomes, and other confounding factors (i.e., cancer type, drug combinations, adjuvant therapies, etc.) preclude a definitive answer as to whether differences exist in the incidence of DOX myotoxicity between sexes. This review summarizes the current clinical and preclinical literature relevant to sex differences in the incidence and severity of DOX myotoxicity, the proposed mechanisms for DOX sexual dimorphism, and the potential for exercise training to serve as an effective therapeutic countermeasure to preserve muscle strength and function in males and females.
... 44 There is a theoretical side with good acceptance that attributes the differences of strength and body composition to the sex hormones, in which each sex produces predominantly a different type of hormone, thus generating kinetics of muscular strength development and discrepant body composition. [45][46][47] Because of the great differences between their anatomical and physiological conditions, the comparisons between genders become unviable and with little applicability in the praxis of gerontological attention. 35,[48][49][50] In order to generate clinical inferential power, the comparisons were arbitrarily performed within strong and weak groups of women and men, with a statistical difference (P ≤ 0.05) of force between them. ...
Background
Studies in ethnic minority communities with social isolation have low genetic variability. Furthermore, assuming that any attempt to determine ageing by chronological cuts is misleading, it is recommended that functional capacity assessments be performed especially during and at the end of adulthood. Specifically, muscle strength performance is an interesting screening measure of functional capacity because of its association with functional level. However, the behaviour of the muscle strength manifestation between sexes and its association with body composition (BC) parameters in a low genetic variability community are unknown. Therefore, the objective of this study was to verify the influence of BC and sex on the handgrip strength of mature remaining Quilombolas.
Methods
Seventy Quilombola volunteers of both sexes (♀ = 39; ♂ = 31) were recruited. BC and muscle strength were tested by dual‐energy X‐ray absorptiometry (DEXA) and handgrip equipment (Jamar), respectively. Correlations between muscle strength and age and BC parameters were determined by Spearman equation. In addition, it has executed comparisons of BC and age between strongest and weakest men and women from the interquartile analysis by Mann–Whitney U test. The significance level was adopted: P ≤ 0.05.
Results
Of the 70 remaining Quilombolas, with a mean age 64.6 ± 7.07 years, 55.7% were women with a mean age of 63.77 ± 7.56 years and 44.3% men with 65.65 ± 7.87 years. Statistical differences were identified for all parameters of BC and performance evaluated between men and women, except for the ratio of appendicular and axial fat‐free mass (P = 0.183). The evaluation of the influence of BC on strength identified that Quilombola men and women have different processes in the decline of strength, considering both the correlation's tests and the comparisons between groups of different degrees of strength.
Conclusions
For Quilombola individuals, strength is a variable that can be modulated due to the influence of gender and BC.
... With its high prevalence and proved impact on disability and hospitalization risk, quality of life and mortality, sarcopenia poses a major health issue for older people and a public health burden [3][4][5][6]. The pathogenesis of this disorder comprises of various factors and mechanisms [7,8], including genetic variability [9,10], cytokine activity [11][12][13], vitamin D, testosterone and growth hormone deficiency [14][15][16][17], mitochondrial dysfunction and apoptosis [18][19][20], muscle disuse [15,21,22], nutritional status [23,24], atherosclerosis [25,26] and diabetes [27,28]. Some authors distinguish primary (or age-related sarcopenia), occurring in otherwise healthy, usually aged persons, from secondary transcriptional factors, such as myocyte enhancing factor 2 (MEF2), peroxisome proliferator-activated receptor gamma (PPARγ), MyoD and NF-κB, as well as a mechanism for myostatin upregulation by glucocorticoids [62]. ...
Sarcopenia is a geriatric syndrome with a significant impact on older patients’ quality of life, morbidity and mortality. Despite the new available criteria, its early diagnosis remains difficult, highlighting the necessity of looking for a valid muscle wasting biomarker. Myostatin, a muscle mass negative regulator, is one of the potential candidates. The aim of this work is to point out various factors affecting the potential of myostatin as a biomarker of muscle wasting. Based on the literature review, we can say that recent studies produced conflicting results and revealed a number of potential confounding factors influencing their use in sarcopenia diagnosing. These factors include physiological variables (such as age, sex and physical activity) as well as a variety of disorders (including heart failure, metabolic syndrome, kidney failure and inflammatory diseases) and differences in laboratory measurement methodology. Our conclusion is that although myostatin alone might not prove to be a feasible biomarker, it could become an important part of a recently proposed panel of muscle wasting biomarkers. However, a thorough understanding of the interrelationship of these markers, as well as establishing a valid measurement methodology for myostatin and revising current research data in the light of new criteria of sarcopenia, is needed.
... Positive associations of serum levels of total T, bioavailable T and/or free T with indices of muscle strength (i.e. handgrip strength and/or leg strength) have been reported for several cohorts of older men 27,31,37 . In the MrOS US and the MrOS Hong-Kong cohorts men with higher bioavailable T and free T, ...
Background
Cognitive decline and impairment of physical performance and mobility are age‐related clinical problems with major negative impact on quality of life of elderly men. In how far the decline of testosterone (T) production contributes to these problems in older men and whether T therapy can contribute to slow‐down, prevent or reverse their development remains subjects of debate.
Methods
This narrative review presents the current knowledge on association of sex steroid status with cognitive decline and impairment of physical function and mobility in elderly men and on the effects of T therapy on cognition and on physical performance and mobility in elderly men. Primary focus is on evidence from larger prospective observational studies and from controlled randomized trials, respectively.
Results
In most observational studies T levels do not predict cognitive decline or development of Alzheimer’s disease. In randomized trials T therapy did not significantly affect cognition in men with low or low‐to‐normal serum T, regardless of whether they have preexisting cognitive impairment. Overall, observational data indicate that the usually moderate decline of androgen exposure in older men cannot fully account for the parallel decline of physical performance and mobility. Trials of T therapy in older men with low or low‐normal serum T, whether they were generally healthy or suffered from physical function impairments, either did not show any effect on mobility and physical performance or showed limited effects of uncertain clinical relevancy.
Conclusions
The whole of the evidence tends to downplay the role of sex steroid status in the decline of cognitive function and impairment of physical function and mobility in older men. Based on the available evidence, prevention or treatment of cognitive decline or of impairment of mobility and physical function are not valid indications for T treatment in older men with low or low‐to‐normal serum T levels.
... In women, declining estrogen levels after menopause result in increased body weight and fat mass as well as shifts in the accumulation of fat from subcutaneous to visceral deposits (126,127). In older men, total testosterone levels decline by about 1% per year of age, with lower levels associated with sarcopenia, lower muscle strength, poorer physical performance, and increased fall risk (128)(129)(130). Randomized controlled trials of various formulations of testosterone supplementation in older men have reported improvements in body composition including increased lean body mass and reduced fat mass (131,132). ...
Sarcopenia is defined as the age-related loss of muscle mass and strength or physical performance. Increased amounts of adipose tissue often accompany sarcopenia, a condition referred to as sarcopenic obesity. The prevalence of sarcopenic obesity among adults is rapidly increasing worldwide. However, the lack of a universal definition of sarcopenia limits comparisons between studies. Sarcopenia and obesity have similar pathophysiologic factors, including lifestyle behaviors, hormones, and immunological factors, all of which may synergistically affect the risk of developing a series of adverse health issues. Increasing evidence has shown that sarcopenic obesity is associated with accelerated functional decline and increased risks of cardiometabolic diseases and mortality. Therefore, the identification of sarcopenic obesity may be critical for clinicians in aging societies. In this review, we discuss the effect of sarcopenic obesity on multiple health outcomes and its role as a predictor of these outcomes based on the components of sarcopenia, including muscle mass, muscle strength, and physical performance.
... For example, de Carvalho et al. [8] found that abdominal obesity is associated with lower HGS, accelerating the decline of muscle strength. A possible explanation for this phenomenon is that excessive adiposity can downregulate the anabolic actions of testosterone [34], growth hormones [35], and insulin [36], which may contribute to a progressive loss of muscle mass and associated function in both sexes. Additionally, excessive adipose tissue can induce a proinflammatory state by the action of several cytokines (e.g., higher plasma concentrations of tumor necrosis factor-alpha and interleukin-6), which is associated with lower muscle strength [37] and disability in older adults [38]. ...
Normal-weight obesity (NWO) syndrome has been shown to be associated with cardiometabolic dysfunction. However, little is known regarding this potential relationship in Latin American children and adolescents. The aim of this study was two-fold: (i) to investigate whether Colombian youth with NWO syndrome have a poorer cardiometabolic profile and physical fitness performance than normal-weight lean (NWL) peers; and (ii) to determine if physical fitness levels are related to prevalence of normal-weight obesity in youth. This was an analytical cross-sectional study of 1919 youths (9–17.9 years old, 53.0% girls) in the capital area of Colombia. NWO was defined as a body mass index <25 kg/m2 and a validated body fat percentage above the sex-age-specific 90th percentile for Colombian children and adolescents. Body fat was estimated using bioelectrical impedance analysis, cardiorespiratory fitness (CRF) was estimated using the 20-meter shuttle run test, and muscular fitness with the handgrip test. Biochemical profile blood samples were collected for cardiometabolic risk factors. After adjusting for chronological age, pubertal stage, and Mediterranean diet adherence, the NWO group (boys and girls) had significantly higher values for cardiometabolic risk factors, and waist circumference (WC) than the NWL group. The prevalence of NWO was lower in youth classified with healthy CRF (boys, odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37 to 0.78; girls, OR = 0.35, 95% CI 0.24 to 0.50), p < 0.001. Our findings indicate that using only body mass index for the assessment of cardiometabolic risk likely misrepresents true adiposity and suggest the need to include the assessment of body fat in the routine clinical evaluation of individuals during childhood and adolescence.
... For example, de Carvalho et al. [8] found that abdominal obesity is associated with lower HGS, accelerating the decline of muscle strength. A possible explanation for this phenomenon is that excessive adiposity can downregulate the anabolic actions of testosterone [34], growth hormones [35], and insulin [36], which may contribute to a progressive loss of muscle mass and associated function in both sexes. Additionally, excessive adipose tissue can induce a proinflammatory state by the action of several cytokines (e.g., higher plasma concentrations of tumor necrosis factor-alpha and interleukin-6), which is associated with lower muscle strength [37] and disability in older adults [38]. ...
The adverse effects of fat mass on functional dependence might be attenuated or worsened, depending on the level of muscular strength. The aim of this study was to determine (i) the detrimental effect of excess adiposity on dependence in activities of daily living (ADL), and (ii) whether relative handgrip strength (HGS) moderates the adverse effect of excess adiposity on dependence, and to provide the threshold of relative HGS from which the adverse effect could be improved or worsened. A total of 4169 participants (69.3 ± 7.0 years old) from 244 municipalities were selected following a multistage area probability sampling design. Measurements included anthropometric/adiposity markers (weight, height, body mass index, waist circumference, and waist-to-height ratio (WHtR)), HGS, sarcopenia “proxy” (calf circumference), and ADL (Barthel Index scale). Moderation analyses were performed to identify associations between the independent variable (WHtR) and outcomes (dependence), as well as to determine whether relative HGS moderates the relationship between excess adiposity and dependence. The present study demonstrated that (i) the adverse effect of having a higher WHtR level on dependence in ADL was moderated by relative HGS, and (ii) two moderation thresholds of relative HGS were estimated: 0.35, below which the adverse effect of WHtR levels on dependency is aggravated, and 0.62, above which the adverse effect of fat on dependency could be improved. Because muscular strength represents a critically important and modifiable predictor of ADL, and the increase in adiposity is inherent in aging, our results underscore the importance of an optimal level of relative HGS in the older adult population.
... Furthermore, muscle mass is linked to total, free, and bioavailable testosterone levels among older men 15,30 and to free testosterone levels among postmenopausal women 31 . Muscle strength and physical performance are correlated with the total, free, and bioavailable testosterone levels among older men 15,16,32 , but no correlation among older women 33 . Notably, plasma total and free testosterone levels are associated with instrumental activities of daily living (IADL) among elderly men, but no association between testosterone levels and IADL among elderly women is observed 34 . ...
This study aimed to explore the combined effects of having sleep problems and taking sleeping pills on the skeletal muscle mass and performance of community-dwelling elders. A total of 826 participants who have complete information regarding dual-energy X-ray absorptiometry examination, questionnaire, and physical performance tests were included. The status of having sleep problems and taking sleeping pills was assessed with a self-reported questionnaire. The prevalence rates of sleep problems among older men and women were 37.4% and 54.5%, respectively. After multivariate adjustment, the mean height-adjusted skeletal muscle indices for elders having sleep problems and taking sleeping pills among men and women were 7.29 and 5.66 kg/m2, respectively, which were lower than those without sleep problems (P = 0.0021 and P = 0.0175). The performance of the older men having sleep problems and taking sleeping pills in terms of walking speed, grip strength, and number of squats, was poorer than those of the older men without sleep problems. The status of having sleep problems and taking sleeping pills was correlated with low skeletal muscle mass and poor physical performance in community-dwelling elders. These findings suggest that having sleep problems and taking sleeping pills are associated with having sarcopenia among community elderly.
... Also studies have indicated significant relation of sex hormones with muscle mass and strength, but not with physical activity (14)(15)(16). In different studies, plasma sex hormone levels have been proposed to be positively or inversely related to muscle mass and strength, as well as physical activity (17)(18)(19). Given the mixed and contradictory results, the current study was not in support of applying these sex hormones to improving activity of daily living in Chinese female centenarians. ...
Background
Activity of daily living declines in female elderly, which not only increases hospitalization and mortality rates, but also aggravates individual and societal burden. Large samples are needed to elucidate the relationships of plasma sex hormone levels with activity of daily living in Chinese female centenarians to better understand the effects of hormone-replacing therapy.
Objective
As the first time in the world, the current study was designed to investigate the relationships of plasma sex hormone levels with activity of daily living in Chinese female centenarians.
Participants
China Hainan Centenarian Cohort Study was carried out in 18 cities and counties of Hainan Province.
Main measures
Home interview, physical examination and blood analysis were carried out in 583 female centenarians following standard procedures. Barthel Index was used to assess the activity of daily living.
Key results
Median age of all female centenarians was 102 years, with the range from 100 to 115 years. Median values of Barthel Index were 85(60–90). In multivariate linear regression analyses, Barthel Index values were inversely associated with plasma luteinizing hormone (LH), follicle-simulating hormone (FSH), testosterone, progesterone and estradiol levels (P<0.05 for all).
Conclusion
Plasma sex hormone levels, including LH, FSH, testosterone, progesterone and estradiol, had significant relationships with activity of daily living in Chinese female centenarians.
... Another cross-sectional study of 1489 older men by TungWai Auyeung found that high serum testosterone concentration was correlated with not only greater muscle power and mass but also better physical functioning. Similarly, a study [12] showed that lower levels of sex hormones in men were accompanied by impaired physical functioning and weak muscle power. Conversely to our study with healthy participants, Loncar et al.'s study [13] declared that the testosterone level had no correlation with grip strength in patients with heart failure. ...
Background: Skeletal muscle is an important site for storing proteins and providing general physical function. Recent research has shown that muscle strength decreases earlier than muscle mass decreases, as shown during the aging process. Our article aimed to compare the association between testosterone levels and grip strength to provide an earlier biomarker to detect muscle weakness.
Method: We adopted quartile-based analysis by dividing handgrip power into quartiles, with all participants in the lowest quartile serving as the reference group. Linear regression analysis was conducted between handgrip power and testosterone. Logistic regression models were used to analyze the longitudinal correlation between testosterone levels and the presence of low muscle strength.
Results: Serum testosterone levels had a significant correlation with grip strength in all models (p < .001). In addition, high testosterone levels were negatively associated with low muscle strength in all groups (p < .001). A stronger relationship was observed between testosterone levels and grip strength among non-obese participants than among obese participants.
Conclusions: In conclusion, our study highlighted that testosterone levels are related to greater grip strength.
... Differences in DHEAS level between sexes had been described by Orentreich N et al 4 . Further studies by Schaap LA et al., found an association between DHEAS level and physical performance in men but not in women 9 . While we found an association between frailty and DHEAS level, the association did not differ by gender. ...
Objective: To determine the association between dehydroepiandrosterone and frailty in the elderly.
Methods: In this cross-sectional analytical study, older people aged 65 and above attending the geriatric outpatient and inpatient services were screened for frailty using Fried's criteria. The frailty phenotype criteria include unintentional weight loss, slow walking speed, self-reported exhaustion, reduced grip strength and reduced physical activity. Subjects having 3 of the 5 criteria are termed as frail and having 1 or 2 criteria are termed as intermediate-frail and having none of the criteria is termed as non-frail, 33 frail, 34 intermediate-frail and 33 non-frail subjects were randomly selected from the screened subjects to participate in the study. Dehydroepiandrosterone sulphate ester (DHEAS) level in all the study subjects was measured.
Results: Of the 100 study subjects, 53 were males, and 47 were females. The mean age of the study participants was 77.12 years. The frailty phenotype increased with advancing age. The mean DHEAS level was 49.55μg/dL We found an inverse relationship between the frailty categories and the DHEAS level. No gender interaction was observed in the association between frailty and DHEAS level. BMI ≥ 29 kg/m2 attenuated the association found between frailty and DHEAS level.
Conclusion: In this study, we found an association between frailty and DHEAS level. The DHEAS level in the frail group was lower when compared with those of the non-frail group.
... Testosterone is the primary male sex hormone secreted by testis interstitial cells and has a wide variety of effects on sex differentiation (Isidori et al., 2005), fat deposition (Mammi et al., 2011;Kelly and Jones, 2013), muscle growth (Schaap et al., 2005), the cardiovascular system (Reckelhoff, 2005;Lopes et al., 2012), and the immune system (Trigunaite et al., 2015). In the cell cytoplasm, testosterone is often converted by 5α-reductase to the more active form, dihydrotestosterone (DHT). ...
Mammalian mitochondrial biogenesis is a complex process involving mitochondrial proliferation and differentiation. Mitochondrial DNA transcription factor A (TFAM), which encodes a major component of a protein-mitochondrial DNA (mtDNA) complex, is regulated by peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Testosterone is the primary male sex hormone and plays an increasingly important role in mammalian development through its interaction with androgen receptor (AR). However, the function of AR in mitochondrial biogenesis induced by testosterone deficiency has not been investigated. Here, we explored the molecular mechanism underlying the effect of testosterone deficiency on mitochondrial biogenesis using a Yorkshire boar model. Testosterone deficiency caused by castration induced changes in mtDNA copy numbers in various tissues, and AR showed the opposite tendency to that of mtDNA copy number, particularly in adipose tissues and muscle tissues. In addition, castration weakened the correlation of PGC1α and mtDNA copy number, while AR and TFAM showed a relatively high correlation in both control and castrated pigs. Furthermore, luciferase assays revealed that AR binds to potential AR elements in the TFAM promoter to promote TFAM expression. Taken together, testosterone may be involved in the pathway linking PGC1α to mitochondrial biogenesis through the interaction between AR and TFAM.
... In women, T levels drop rapidly from 20 to 45 years of age [148]. High levels of these anabolic hormones are positively associated with elevated muscle strength and may therefore contribute to muscle improvement in obese individuals [149][150][151]. In young men, low T secretion results in decreased muscle mass and strength, and T replacement therapy increases muscle mass, increases the sensibility of T receptors and restores muscle strength [152,153]. ...
... In women, T levels drop rapidly from 20 to 45 years of age [148]. High levels of these anabolic hormones are positively associated with elevated muscle strength and may therefore contribute to muscle improvement in obese individuals [149][150][151]. In young men, low T secretion results in decreased muscle mass and strength, and T replacement therapy increases muscle mass, increases the sensibility of T receptors and restores muscle strength [152,153]. ...
Although there are several reviews that report the interrelationship between sarcopenia and obesity and insulin resistance, the relation between sarcopenia and the other signs that compose the metabolic syndrome (MetS) has not been extensively revised. Here, we review the mechanisms underlying MetS-related sarcopenia and discuss the possible therapeutic measures proposed. A vicious cycle between the loss of muscle and the accumulation of intramuscular fat might be associated with MetS via a complex interplay of factors including nutritional intake, physical activity, body fat, oxidative stress, proinflammatory cytokines, insulin resistance, hormonal changes, and mitochondrial dysfunction. The enormous differences in lipid storage capacities between the two genders and elevated amounts of endogenous fat having lipotoxic effects that lead to the loss of muscle mass are discussed. The important repercussions of MetS-related sarcopenia on other illnesses that lead to increased disability, morbidity, and mortality are also addressed. Additional research is needed to better understand the pathophysiology of MetS-related sarcopenia and its consequences. Although there is currently no consensus on the treatment, lifestyle changes including diet and power exercise seem to be the best options.
... In young men undergoing anterior cruciate ligament reconstruction, perioperative testosterone supplementation increased lean mass at 6 weeks (19). Physiological levels of testosterone were associated positively with lean mass in younger and older men (20)(21)(22), and baseline serum testosterone and 17b-estradiol levels were associated positively with handgrip strength in older men (23). Longitudinal data suggest that high baseline serum testosterone levels may protect elderly men against frailty (24)(25)(26)(27)(28). ...
Context
Sex steroid hormones exhibit anabolic effects whereas a deficiency engenders sarcopenia. Moreover, supra-physiological levels of glucocorticoids promote skeletal muscle atrophy, while physiologic levels of glucocorticoids may improve muscle performance.
Objective
To study the relationship between both groups of steroid hormones at a physiological range with skeletal muscle mass and function in the general population.
Design
Cross-sectional analysis of the associations between urinary excreted androgens, estrogens, glucocorticoids and steroid hormone metabolite ratios with lean mass and handgrip strength in a population-based cohort.
Setting
Three centers in Switzerland including 1128 participants.
Measures
Urinary steroid hormone metabolite excretion by GC-MS, lean mass by bioimpedance analysis and isometric handgrip strength by dynamometry.
Results
For lean mass a strong positive association was found with 11β-OH-androsterone and with most glucocorticoids. Androsterone showed a positive association in middle-aged and older adults. Estriol showed a positive association only in men. For handgrip strength strong positive associations with androgens were found in middle-aged and older adults, whereas positive associations were found with cortisol metabolites in young to middle-aged adults.
Conclusions
Sex steroid and glucocorticoids are strongly positively associated with skeletal muscle mass and strength in the upper limbs. The associations with muscle strength appear to be independent of muscle mass. Steroid hormones exert age-specific anabolic effects on lean mass and handgrip strength: Deficits in physical performance of aged muscles may be attenuated by androgens, whereas glucocorticoids in a physiological range increase skeletal muscle mass at all ages, and muscle strength in particular in younger adults.
... The sex hormone distribution in prenatal period is significantly correlated with the incidence of various mental disorders (such as autism, dyslexia, migraine, stammering) but also immune dysfunction [12], myocardial infarction [13], breast and prostate cancer [14,15] facial attractiveness [16] or hand grip strength [17]. Therefore the 2D:4D digit ratio may serve as an indicator of the risk of certain diseases, attractiveness [18] or of the general biological condition [15,18]. ...
The 2D:4D digit ratio (in the right hand) in the analysed group of children at the age 6–13 years is significantly differentiated depending on sex; boys are characterised by lower values of the indicator.
The muscle mass variability of girls is also dependent on the proportion of sex hormones in prenatal life, which is visible as the value of the 2D:4D digit ratio.
We have found no relationship between the 2D:4D digit ratio values and the relative body weight and the WHR in both sexes what is inconsistent result with some previous studies.
Maternal traits, such as maternal education and maternal weight gain during pregnancy, significantly modify the body composition in the group of girls aged 6–13 years.
... Hormonal changes contribute to the onset of SO, as determined by epidemiological investigations of Asian people: high levels of serum insulin are positively correlated with SO, while low levels of 25-OH-vitamin D are negatively correlated with SO [8,9] . Some prospective studies have shown that low levels of testicular hormone and growth hormone result in decreased muscle mass in SO patients [10,11] . Other investigations have revealed that low amounts of exercise and protein intake may induce SO [12,13] . ...
Objective:
Aging which is accompanied by loss of skeletal muscle and increase of body fat in some adults older than 60 years does not only result in remarkable influences on daily life function but also increases the risk of cardiovascular events. This study used electrical acupuncture together with essential amino acid supplementation to treat sarcopenic obesity (SO) in male older adults.
Methods:
A total of 48 male participants with SO (>60 years old) were randomized to electrical acupuncture with oral essential amino acids (EA + AA) or oral essential amino acids alone (AA). Acupuncture points on the limbs were punctured and stimulated electrically once every 3 days for 12 weeks. All participants received essential amino acids orally, twice per day for 28 weeks. Body fat percentage (BFP) and appendicular skeletal muscle index (ASM/H2) was determined by bioelectrical impedance analysis.
Results:
Both groups exhibited significant changes in BFP after 12, 20, and 28 weeks compared with baseline values; for ASM/H2, there were significant differences to baseline values after 12, 20, and 28 weeks in the EA + AA group, but only after 28 weeks in the AA group. Between the two groups, there were significant differences in BFP after 12, 20, and 28 weeks, and in ASM/H2 after 20 and 28 weeks.
Conclusion:
Both methods decrease BFP and increase ASM/H2. In male older adults, electrical acupuncture with oral essential amino acids is more effective and can increase muscle mass in a shorter time than oral essential amino acids alone.
Background
There is growing recognition of the importance of sex and gender differences within falls literature, but the characterization of such literature is uncertain. The aim of this scoping review was to (1) map the nature and extent of falls literature examining sex or gender differences among older adults, and (2) identify gaps and opportunities for further research and practice.
Methods
We used a scoping review methodology. Eligible studies included participants with a mean age of 60 years and study aims specifying falls and either sex or gender concepts. MEDLINE, Embase, CINAHL, Ageline, and Psychinfo databases were searched from inception to March 2, 2022. Records were screened and charted by six independent reviewers. Descriptive and narrative reports were generated.
Results
A total of 15,266 records were screened and 74 studies were included. Most studies reported on sex and gender differences in fall risk factors ( n = 52, 70%), incidence/prevalence ( n = 26, 35%), fall consequences ( n = 22, 30%), and fall characteristics ( n = 15, 20%). The majority of studies ( n = 70, 95%) found significant sex or gender differences in relation to falls, with 39 (53%) identifying significant sex differences and 31 (42%) identifying significant gender differences. However, only three (4%) studies defined sex or gender concepts and only nine (12%) studies used sex or gender terms appropriately. Fifty‐six (76%) studies had more female participants than males. Four (5%) were intervention studies. Studies did not report falls in line with guidelines nor use common fall definitions.
Conclusion
Sex and gender differences are commonly reported in falls literature. It is critical for future research to use sex and gender terms appropriately and include similar sample sizes across all genders and sexes. In addition, there is a need to examine more gender‐diverse populations and to develop interventions to prevent falls that address sex and gender differences among older adults.
Objectives:
This study aimed to evaluate the endogenous hormonal factors related to dominant handgrip strength (HGS) in postmenopausal women.
Methods:
A cross-sectional study was performed on 402 postmenopausal women aged 47 to 83 years. The following variables were recorded: age, age at menopause, smoking status, adiposity, HGS, and physical activity. Hormonal parameters (follicle-stimulating hormone, estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate, Δ4 androstenedione, insulin-like growth factor-1 [IGF-1], vitamin D, and parathormone levels) were measured and results reported as odds ratios (ORs), β coefficients and 95% confidence interval (95% CI). A directed acyclic graph was used to identify potential confounding variables and was adjusted in the regression model to assess associations between endogenous hormones and HGS.
Results:
The mean dominant HGS was 22.8 ± 3.7 kg, and 25.6% of women had dynapenia. There were significant differences in plasma levels of follicle-stimulating hormone (OR, 0.99; 95% CI, 0.98-1.00), cortisol (OR, 1.07; 95% CI, 1.02-1.12), and dehydroepiandrosterone sulfate (OR, 0.99; 95% CI, 0.98-1.00) between women with normal HGS and those who presented with dynapenia. After adjusting for confounding variables, no significant association was found between endogenous hormones and HGS.
Conclusions:
Our results showed that studied ovarian steroids, adrenal hormones, IGF-1, parathormone, and vitamin D were not associated with HGS.
The clinical manifestation of osteopenia/osteoporosis is the fragility fracture, which is associated with significant morbidity and mortality. It also causes a high risk of disability. Fragility fractures may occur spontaneously but most frequently they are the consequence of falls. Sarcopenia, the age-related loss of muscle mass and physical performance, is becoming an increasing medical and financial concern in aging societies. Sarcopenia is evident in around 20% of over 70-year-olds; the figure rises to 50% for those over the age of 80. Those affected by this syndrome exhibit impaired mobility, a higher disability rate, and also a higher risk for falls and fractures. There is an intensive and complex interaction, between bones and muscles, with a magnified negative impact on the individual health. Individuals suffering from both, sarcopenia and osteopenia, are identified as osteosarcopenic or sarcoosteopenic. Fracture risk is increased 3.5-fold in male osteosarcopenia patients and herewith significantly higher than in sarcopenia and osteopenia alone. The importance of osteosarcopenia is not just linked to such potential additive risk of negative functional outcome, but also the suggestion that osteosarcopenia results from progression of osteopenia and/or sarcopenia. Consequently, therapeutic interventions (nutrition, exercise, vitamin D) should be started early in the development of this “hazardous duet” in a trial to prevent or at least stop such negative synergistic effects of osteosarcopenia on physical performance and bone turnover. This chapter starts by discussing osteosarcopenia and the impact of aging on the human body and the potential mechanisms of age-related sarcopenia. It then highlights the biochemical communication between muscle and bone and how muscle and bone act as an endocrine organ. The chapter then discusses osteosarcopenia is standard practice, presenting a case finding practical algorithm as well as categories of sarcopenia and sarcopenia-like conditions. This is followed by tools of diagnosis and treatment protocols of osteosarcopenia. The chapter concludes by presenting patient-centered care approach for osteosarcopenia patients.
Background and objectives:
Several cross-sectional and prospective longitudinal studies have shown a progressive decline in Serum (S) Testosterone levels with an increase in age. The clinical consequence of this decline in S Testosterone is not clear from the prevailing data. Several ageing features like decreased libido, Osteo-sarcopenia, anemia, and depressed mood may be associated with reduced androgen levels in elderly males. This study was aimed to study the prevalence of androgen deficiency in elderly males more than 60 years of age presenting to the outpatient department of a tertiary care hospital and its association with frailty and mobility.
Methods:
A cross-sectional observational study was conducted over two years at a tertiary care hospital in Pune, India. The participants underwent a detailed history and physical examination. Biochemical tests and S total testosterone estimation was done. Mobility was estimated by calculating the time taken to perform the Timed Up and Go test (TUGT). Frailty was calculated by Fried's frailty index. Data are presented as mean ± standard deviation, and a comparison between the groups was made using Mann-Whitney U-test. The categorical variables are presented in frequencies along with respective percentages and were compared using the Chi-square or Fisher's exact test. The data was analyzed using SPSS version 22. A P <.05 was considered statistically significant in all the tests.
Results:
The mean age of the study participants was 68.37 ± 6.3 years, with a range of 60-88 years. The mean S total testosterone levels were 3.95 ± 2.06 ng/ml with a range of 0.04-25.36 ng/ml. As per the study definition, Ninety-two (21.67%) participants had testosterone deficiency. Three hundred and thirty-three (78.5%) participants had impaired motility represented by a TUGT time of more than 12 seconds. The Frailty index calculated revealed 94 (22.2%) of the study participants to be normal, 263 (62%) to be vulnerable, and 67 (15.8%) of the patients to be frail.
Conclusion:
The prevalence of testosterone deficiency in the elderly male population was 21.67%. However, there was no association of testosterone deficiency with frailty or impaired mobility. Furthermore, testosterone deficiency was not associated with BMI and hemoglobin levels. In the elderly, testosterone deficiency is associated with low bone mass and therefore imply an increased risk of osteoporotic fractures.
Aim:
Although menstrual/reproductive factors are known to be associated with physical disability, little is known about these associations in relation to activities of daily living (ADL). This study aimed to clarify associations between menstrual/reproductive factors and ADL limitations in peri- and postmenopausal women.
Study design:
A nested case-control study of the Japan Public Health Center-based Prospective (JPHC) Study.
Methods:
The main outcome measure was self-reported ADL levels in the 10-year follow-up questionnaire survey of the JPHC Study conducted between 2000 and 2004 (N = 36 460). Women who "live inside almost independently, but go out with assistance" or had a lower level of activity were considered to have ADL limitations ("cases"), and all others served as controls. Candidate menstrual/reproductive predictors were as follows: menarcheal age, menopausal status, menopausal age, regularity of menses, menstrual cycle, number of pregnancies, age at first pregnancy, number of deliveries, age at first delivery, and breast feeding. Multiple logistic regression analyses were conducted, and odds ratios adjusted for age and past lifestyle were calculated.
Results:
Mean ages of cases (N = 592) and controls (N = 38 656) were 68.3 (SD = 7.6) and 61.1 (SD = 7.7) years, respectively. With respect to menopausal age, groups aged <45 and ≥55 years had significantly higher adjusted ORs (1.44, 95% CI: 1.09-1.90 and 1.55, 95%CI: 1.09-2.18, respectively) than the reference group (50-54 years). Multiparous women had significantly lower ORs than nulliparous women.
Conclusion:
Our findings suggest that menopausal age and parity may predict future ADL limitations in women.
Background
Ageing is associated with body composition changes that include a reduction of muscle mass or sarcopenia and an increase in visceral obesity. Thus, ageing involves a muscle-fat imbalance with a shift towards more fat and less muscle. Therefore, sarcopenic obesity, defined as a combination of sarcopenia and obesity, is a global health phenomenon due to the increased ageing of the population combined with the increased epidemic of obesity. Previous studies have shown inconsistent association between sarcopenic obesity and the risk of cardiovascular disease (CVD).
Aims
To systematically review the recent literature on the CVD risks associated with sarcopenic obesity and summarises ways of diagnosis and prevention.
Methods
A systematic review of studies that reported the association between sarcopenic obesity and CVD risk in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations.
Results
Risk factors of sarcopenic obesity included genetic factors, ageing, malnutrition, sedentary lifestyle, hormonal deficiencies and other molecular changes. The muscle-fat imbalance with increasing age results in an increase in the pro-inflammatory adipokines secreted by adipocytes and a decline in the anti-inflammatory myokines secreted by myocytes. This imbalance promotes and perpetuates a chronic low-grade inflammatory state that is characteristic of sarcopenic obesity. After application of exclusion criteria, only 12 recent studies were included in this review. The recent studies have shown a consistent association between sarcopenic obesity and cardiovascular disease risk although most of the studies are of cross-sectional design that does not confirm a causal relationship. In addition, most of the population studied were of Asian origin which may limit the generalisability of the results. Non-pharmacological interventions by exercise training and adequate nutrition appear to be useful in maintenance of muscle strength and muscle mass in combination with a reduction of adiposity to promote healthy ageing.
Conclusions
Sarcopenic obesity appears to increase the risk of CVD in older people however, future prospective studies of diverse population are still required. Although non-pharmacologic interventions are useful in reducing the risk of sarcopenic obesity, novel specific pharmacologic agents are lacking.
This narrative review presents an overview of present knowledge on fertility and reproductive hormones changes in aging men, the factors driving and modulating these changes, their clinical consequences, and benefits and risks of testosterone (T) therapy.
Aging is accompanied by moderate decline of gamete quality and fertility. Population mean levels show mild total T decline, SHBG increase, steeper free T decline, and moderate LH increase with important contribution of comorbidities (e.g. obesity) to these changes. Sexual symptoms and lower hematocrit are associated with low T and partly responsive to T therapy. Relationship of serum T with body composition and metabolic health is bidirectional; limited beneficial effects of T therapy on body composition have only marginal effects on metabolic health and physical function. Skeletal changes are associated primarily with estradiol and SHBG. Cognitive decline is not consistently linked to low T and not improved by T therapy. Although limited evidence links moderate androgen decline with depressive symptoms, T therapy has small beneficial effects on mood, depressive symptoms and vitality in elderly with low T. Not optimal T (and/or DHT) has been associated with increased risk of stroke, but not of ischemic heart disease, whereas association with mortality probably reflects that low T is a marker of poor health. Globally, neither severity of clinical consequences attributable to low T, nor nature and magnitude of beneficial treatment effects justify the concept of some broadly applied ‘T replacement therapy’ in older men with low T. Moreover, long-term safety of T therapy is not established.
Background: In nondemented aging, higher levels of everyday physical activity (EPA) and mobility performance are associated with better executive function (EF) trajectories. However, these associations may be moderated by both sex and Alzheimer’s disease (AD) genetic risk.
Objectives: In a longitudinal study, we investigate sex differences in (a) EPA and mobility effects on EF performance (level) and change (slope) and (b) AD genetic risk moderation of these associations. Methods: The longitudinal design included nondemented adults (n = 532, mean age = 70.4 years, range 53–95) from the Victoria Longitudinal Study. Using structural equation analyses on an EF latent variable, we tested (a) sex moderation and (b) interactive effects of sex and APOE on observed EPA-EF and mobility-EF performance and change relationships. Results: First, we observed independent sex effects for the EPA-EF and mobility-EF predictions. Whereas EPA had a significant effect on EF performance and change only for females, mobility had a significant effect for both sexes. Notably, males with lower mobility levels experienced steeper EF decline than females with lower mobility levels. Second, we observed significant sex × APOE interaction effects. The combination of lower genetic risk and higher EPA benefitted females but not males. In contrast, lower genetic risk and higher mobility benefited both sexes, although male APOE no-risk carriers with lower mobility levels had EF decline patterns that were similar to APOE risk carriers.
Conclusions: Longitudinal analyses across a broad band of aging show that sex moderates the effects of both EPA and mobility on EF performance and change. Notably, this moderation occurs differentially across the AD genetic risk status. These results point to a precision health approach to observational and interventional research in which effects of physical activity and mobility on EF trajectories and dementia are examined in the personalized and interactive context of sex and AD risk.
Anemia is a common health problem in older adults and is associated with risk factors for fracture such as low physical function and low bone mass. The aim of this study was to examine the relationship between anemia and fracture risk in older adults. We conducted a retrospective cohort study from 2003 to 2013. The participants were community‐dwelling Korean adults aged 65 years and older who participated in the National Health Screening Program (n = 72,131) between 2003 and 2008. Anemia (<12 g/dL for women and <13 g/dL for men) and severity of anemia (mild: 11g/dL ≤ Hb < 12 g/dL, moderate to severe: Hb < 11g/dL) were defined by World Health Organization (WHO) criteria. The incidence of any fractures, vertebral fractures, and femur fractures was identified using ICD‐10 codes. Cox proportional hazard regression models were used to assess risk of fracture according to anemia. Anemia was associated with increased risk of fracture in men (Any: adjusted hazard ratio [aHR] 1.29; 95% confidence interval [CI], 1.18‐1.41; vertebral: aHR 1.20, 95% CI 1.03‐1.40; femur: aHR 1.71, 95% CI 1.44‐2.04), and less strongly, but still significantly in women (Any: aHR 1.10, 95% CI 1.11‐1.41; vertebral: aHR 1.11, 95% CI 1.03‐1.20; femur: aHR 1.37, 95% CI 1.25‐1.52). Higher risk was observed in subjects with moderate‐to‐severe anemia in both sexes. Considering the high prevalence of anemia in older adults, it is important that health professionals recognize increased fracture risk in older adults with anemia. This article is protected by copyright. All rights reserved
In male mammals, changes at all levels of the hypothalamic-pituitary-testicular axis, including alterations in the GnRH pulse generator, gonadotropin secretion, and testicular steroidogenesis, in addition to alterations of feed-forward and feedback relationships contribute to the age-related decline in circulating testosterone concentrations. The rate of age-related decline in testosterone levels is affected by the presence of chronic illness, adiposity, medication, sampling time, and the methods of testosterone measurement. Epidemiologic surveys reveal an association of low testosterone levels with changes in body composition, physical function and mobility, risk of diabetes, metabolic syndrome, coronary artery disease, and fracture risk. Age-related decline in testosterone should be distinguished from classical hypogonadism due to known diseases of the hypothalamus, pituitary and the testis. In young hypogonadal men who have a known disease of the hypothalamus, pituitary and testis, testosterone therapy is generally beneficial and has been associated with a low frequency of adverse events. However, neither the long-term benefits in improved health outcomes nor the long-term risks of testosterone therapy are known in older men with age-related decline in testosterone levels. Well-conducted studies of up to one-year duration have found improvements in sexual desire, erectile function, and overall sexual activity; mobility; and volumetric bone density, and correction of anemia with testosterone replacement of older men with unequivocally low testosterone levels. Although testicular morphology, semen production, and fertility are maintained up to a very old age in men, there is clear evidence of decreased fecundity with advancing age and an increased risk of specific genetic disorders related to paternal age among the offspring of older men. Thus, reproductive aging of men is emerging as an important public health problem whose serious societal consequences go far beyond the quality of life issues related to low testosterone levels.
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The decline in skeletal muscle mass and function with age is referred as sarcopenia. It is characterized by the muscle fiber's quality, strength, muscle endurance and metabolic ability decreasing as well as the fat and connective tissue growing. Previous studies have shown that sarcopenia in itself features decreased number and cross-sectional area of muscle fibers and the net degradation of protein, which results from the joint effects of multiple factors such as the exacerbation of inflammation, oxidative stress injury, mitochondrial dysfunction, abnormal autophagy and dysregulation of muscle quality regulatory factors. In this review, we systematically displayed the molecular mechanism of sarcopenia, which will be helpful to deepen our understanding of sarcopenia and provide potential targets for the prevention and treatment of sarcopenia.
Introduction: Age-related decline in serum testosterone (T) has been suggested in some studies to be associated with individual components of frailty: diminished energy, muscle strength and physical function.
Areas covered: The aim of this study is to comprehensively review evidence from observational and interventional studies on the relationship of T to frailty in older men. We reviewed observational studies exploring the relationship between circulating T and its potent metabolite dihydrotestosterone (DHT) with frailty. We further reviewed the effects of T treatment on lean mass, muscle strength and physical function in both frail and non-frail older men.
Expert commentary: T treatment may provide modest improvements in lean mass among both frail and non-frail older men, but current evidence on the T effect on muscle strength is conflicting and the effect on physical function is weak.
Frailty is a condition characterized by a high vulnerability to low-power stressors affecting around 10% of people older than 65 years.
Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons.
This prospective cohort study included men and women 71 years of age or older who were living in the community, who reported no disability in the activities of daily living, and who reported that they were able to walk one-half mile (0.8 km) and climb stairs without assistance. The subjects completed a short battery of physical-performance tests and participated in a follow-up interview four years later. The tests included an assessment of standing balance, a timed 8-ft (2.4-m) walk at a normal pace, and a timed test of five repetitions of rising from a chair and sitting down.
Among the 1122 subjects who were not disabled at base line and who participated in the four-year follow-up, lower scores on the base-line performance tests were associated with a statistically significant, graduated increase in the frequency of disability in the activities of daily living and mobility-related disability at follow-up. After adjustment for age, sex, and the presence of chronic disease, those with the lowest scores on the performance tests were 4.2 to 4.9 times as likely to have disability at four years as those with the highest performance scores, and those with intermediate performance scores were 1.6 to 1.8 times as likely to have disability.
Among nondisabled older persons living in the community, objective measures of lower-extremity function were highly predictive of subsequent disability. Measures of physical performance may identify older persons with a preclinical stage of disability who may benefit from interventions to prevent the development of frank disability.
A short battery of physical performance tests was used to assess lower extremity function in more than 5,000 persons age 71 years and older in three communities.
Balance, gait, strength, and endurance were evaluated by examining ability to stand with the feet together in the side-by-side, semi-tandem, and tandem positions, time to walk 8 feet, and time to rise from a chair and return to the seated position 5 times.
A wide distribution of performance was observed for each test. Each test and a summary performance scale, created by summing categorical rankings of performance on each test, were strongly associated with self-report of disability. Both self-report items and performance tests were independent predictors of short-term mortality and nursing home admission in multivariate analyses. However, evidence is presented that the performance tests provide information not available from self-report items. Of particular importance is the finding that in those at the high end of the functional spectrum, who reported almost no disability, the performance test scores distinguished a gradient of risk for mortality and nursing home admission. Additionally, within subgroups with identical self-report profiles, there were systematic differences in physical performance related to age and sex.
This study provides evidence that performance measures can validly characterize older persons across a broad spectrum of lower extremity function. Performance and self-report measures may complement each other in providing useful information about functional status.
A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population.
Fifteen hypogonadal men (mean age 68 ± 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65± 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone <60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory.
Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean ± sem: −2.0 ± 0.9 ng/dL vs. 0.8 ± 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit.
Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.
A randomized open trial of hormone replacement therapy was used to assess changes in adductor pollicis muscle strength during 6-12 months of treatment with Prempak C 0.625(R) in comparison with an untreated control group. Muscle strength (maximal voluntary force; MVF), muscle cross-sectional area and bone mineral density were measured. Women entering the trial had oestrogen levels below 150 pmol.l-1, confirming their post-menopausal hormonal status. In the treated group, MVF increased by 12.4+/-1.0% (mean+/-S.E.M.) of initial MVF over the duration of treatment, while it declined slightly (2.9+/-0.9%) in the control group. This increase in strength could not be explained by an increase in muscle bulk, there being no significant increase in cross-sectional area during the study. Those subjects who were weakest at enrolment showed the greatest increases in muscle strength after treatment. Bone mineral density in total hip, Ward's triangle and total spine increased in the treated group, in agreement with previous studies. There was no correlation between the individual increases in bone mineral density and those in MVF.
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, β = 1.93 ± 0.52, P < 0.001 and β = 0.011 ± 0.002, P < 0.001). An inverse association existed between T and fat mass (β = −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, β = 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.
This large prospective cohort study was undertaken to construct a fall-risk model for elderly. The emphasis of the study rests on easily measurable predictors for any falls and recurrent falls. The occurrence of falls among 1285 community-dwelling elderly aged 65 years and over was followed during 1 year by means of a "fall calendar." Physical, cognitive, emotional and social functioning preceding the registration of falls were studied as potential predictors of fall-risk. Previous falls, visual impairment, urinary incontinence and use of benzodiazepines were the strongest predictors identified in the risk profile model for any falls (area under the curve [AUC] = 0.65), whereas previous falls, visual impairment, urinary incontinence and functional limitations proved to be the strongest predictors in the model for recurrent falls (AUC = 0.71). The probability of recurrent falls for subsequent scores of the screening test ranged from 4.7% (95% Confidence Interval [CI]: 4.0-5.4%) to 46.8% (95% CI: 43.0-50.6%). Our study provides a fall-risk screening test based on four easily measurable predictors that can be used for fall-risk stratification in community-dwelling elderly.
The functional consequences of the age-associated decline in IGF-I are unknown. We hypothesized that low IGF-I levels in older women would be associated with poor muscle strength and mobility. We assessed this question in a population representative of the full spectrum of health in the community, obtaining serum IGF-I levels from women aged 70-79 yr, enrolled in the Women's Health and Aging Study I or II. Cross-sectional analyses were performed using 617 women with IGF-I levels drawn within 90 d of measurement of outcomes. After adjustment for age, there was an association between IGF-I and knee extensor strength (P = 0.004), but not anthropometry or other strength measures. We found a positive relationship between IGF-I levels and walking speed for IGF-I levels below 50 microg/liter (P < 0.001), but no relationship above this threshold. A decline in IGF-I level was associated with self-reported difficulty in mobility tasks. All findings were attenuated after multivariate adjustment. In summary, in a study population including frail and healthy older women, low IGF-I levels were associated with poor knee extensor muscle strength, slow walking speed, and self-reported difficulty with mobility tasks. These findings suggest a role for IGF-I in disability as well as a potential target population for interventions to raise IGF-I levels.
We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism. Twelve older men (> or =60 yr) with serum total testosterone concentrations <17 nmol/l (480 ng/dl) were randomly assigned in double-blind manner to receive either placebo (n = 5) or testosterone enanthate (TE; n = 7) injections. Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point. TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l. Lean body mass (LBM), muscle volume, prostate size, and urinary flow were measured at baseline and at 6 mo. Protein expression of androgen receptor (AR) and insulin-like growth factor I, along with muscle strength and muscle protein metabolism, were measured at baseline and at 1 and 6 mo of treatment. Hematological parameters were followed monthly throughout the study. Older men receiving testosterone increased total and leg LBM, muscle volume, and leg and arm muscle strength after 6 mo. LBM accretion resulted from an increase in muscle protein net balance, due to a decrease in muscle protein breakdown. TE treatment increased expression of AR protein at 1 mo, but expression returned to pre-TE treatment levels by 6 mo. IGF-I protein expression increased at 1 mo and remained increased throughout TE administration. We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength.
To determine whether oxymetholone increases lean body mass (LBM) and skeletal muscle strength in older persons, 31 men 65-80 yr of age were randomized to placebo (group 1) or 50 mg (group 2) or 100 mg (group 3) daily for 12 wk. For the three groups, total LBM increased by 0.0 +/- 0.6, 3.3 +/- 1.2 (P < 0.001), and 4.2 +/- 2.4 kg (P < 0.001), respectively. Trunk fat decreased by 0.2 +/- 0.4, 1.7 +/- 1.0 (P = 0.018), and 2.2 +/- 0.9 kg (P = 0.005) in groups 1, 2, and 3, respectively. Relative increases in 1-repetition maximum (1-RM) strength for biaxial chest press of 8.2 +/- 9.2 and 13.9 +/- 8.1% in the two active treatment groups were significantly different from the change (-0.8 +/- 4.3%) for the placebo group (P < 0.03). For lat pull-down, 1-RM changed by -0.6 +/- 8.3, 8.8 +/- 15.1, and 18.4 +/- 21.0% for the groups, respectively (1-way ANOVA, P = 0.019). The pattern of changes among the groups for LBM and upper-body strength suggested that changes might be related to dose. Alanine aminotransferase increased by 72 +/- 67 U/l in group 3 (P < 0.001), and HDL-cholesterol decreased by -19 +/- 9 and -23 +/- 18 mg/dl in groups 2 and 3, respectively (P = 0.04 and P = 0.008). Thus oxymetholone improved LBM and maximal voluntary muscle strength and decreased fat mass in older men.
The Women's Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life.
The WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women.
Randomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes.
In this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life.
This study analyzes the associations of socioeconomic status (SES), health, and physical activity with maximal isometric strength in 75-year-old men (n = 104) and women (n = 191). Maximal isometric strength was measured with dynamometers; the forces were adjusted using body weight. The maximal forces for women varied from 66% (trunk flexion) to 73% (knee extension) of those of the men. SES was not associated with muscle force. For men the trunk forces and elbow flexion force correlated negatively with the number of chronic diseases, index of musculoskeletal pain, and self-rated health. For women all the strength test results correlated with self-rated health; the other health indicators showed significant correlation with trunk extension force only. For both sexes the physically more active exhibited greater strength. The index of musculoskeletal symptoms explained the variance on trunk force factor in both sexes. It was concluded that a higher level of everyday physical activity and good values in the st...
BACKGROUND: Muscle strength declines with advancing age; the causes of this are uncertain. In women, strength begins to decline around the time of menopause, suggesting that hormonal changes might influence strength. To determine the effect of postmenopausal estrogen use on muscle strength, neuromuscular function, and the risk of falling, we examined 9704 participants aged 65 years or more enrolled in the Study of Osteoporotic Fractures. METHODS: We measured hip abductor, triceps extensor, and hand-grip muscle strength, balance, gait speed, and self-reported functional disability. Falls during the first year of follow-up were determined from postcards that participants mailed every 4 months indicating whether they had fallen in the previous 4 months (> 99% complete follow-up). RESULTS: After adjusting for age, medications, medical history, and personal habits, current estrogen users did not differ in a clinically meaningful way from those who had never used estrogen on tests of hip abductor strength (mean difference, 0.15 kg; 95% confidence interval, -0.05 to 0.34 kg), triceps extensor strength (0.005 kg; -0.17 to 0.18 kg), or grip strength (0.30 kg; 0.00 to 0.59 kg). Gait speed, time to stand five times from a chair, balance, self-reported disability, and incidence of falls (odds ratio, 1.12; 95% confidence interval, 0.87 to 1.44) also did not differ between current users and never users. In addition, current users were similar to past users on all measures. CONCLUSION: We found no evidence that postmenopausal estrogen use has beneficial effects on muscle strength or neuromuscular function or that it reduces the risk of falling. Language: en
This large prospective cohort study was undertaken to construct a fall-risk model for elderly. The emphasis of the study rests on easily measurable predictors for any falls and recurrent falls. The occurrence of falls among 1285 community-dwelling elderly aged 65 years and over was followed during 1 year by means of a “fall calendar.” Physical, cognitive, emotional and social functioning preceding the registration of falls were studied as potential predictors of fall-risk. Previous falls, visual impairment, urinary incontinence and use of benzodiazepines were the strongest predictors identified in the risk profile model for any falls (area under the curve [AUC] = 0.65), whereas previous falls, visual impairment, urinary incontinence and functional limitations proved to be the strongest predictors in the model for recurrent falls (AUC = 0.71). The probability of recurrent falls for subsequent scores of the screening test ranged from 4.7% (95% Confidence Interval [CI]: 4.0–5.4%) to 46.8% (95% CI: 43.0–50.6%). Our study provides a fall-risk screening test based on four easily measurable predictors that can be used for fall-risk stratification in community-dwelling elderly.
The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
OBJECTIVE The purpose of this study was to examine the effect of hormone (oestrogen) replacement therapy (HRT) on the risk of falling among early postmenopausal women.
METHODS We assessed the incidence of falls in HRT users compared to non-users using population-based data from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study. The study group consisted of 9792 postmenopausal women who responded to the OSTPRE baseline and follow-up inquiries.
RESULTS A total of 3049 women reported sustaining a fall during the previous 12 months. The association between current continuous use of HRT and overall risk of falling was non-significant − 9% (P = 0·10). However, current continuous HRT use was associated with a decreased risk (− 30%) of non-slip falls (N = 1129) (P = 0·0001) but not with the risk (+ 9%) of slip falls (N = 1757) (P = 0·23). In early postmenopausal women (time since menopause < 5 years) the protective effect of current continuous HRT was strengthened: the risk of non-slip falls was 71% lower in HRT users than non-users (P = 0·0035) if menopause had occurred within the past 2·5 years, and 43% lower (P = 0·0015) if time since menopause was 2·5–5 years.
CONCLUSION Hormone replacement therapy may reduce the risk of non-slip falls in early postmenopausal women.
Objectives:
Walking disability affects older people's autonomy and well-being. We investigated the relative effect of common chronic diseases and general impairments on walking disability in the general oldest-old population.
Design:
Population-based cohort study.
Setting:
Leiden 85-plus Study, the Netherlands.
Participants:
Five hundred ninety-nine persons aged 85, response rate 87%.
Measurements:
Walking disability was assessed using a 6-meter walking test. Persons with a walking time below the 25th percentile and those who were physically unable to perform the walking test were categorized as having a walking disability. Information on common chronic diseases was obtained from records of subjects' general practitioners and pharmacies. General impairments were assessed with functional tests and standardized questions during face-to-face interviews. We expressed the effect of common chronic diseases and general impairments as the population attributable risk (PAR), indicating how much disability can be prevented when the identified risk factor is eliminated from the population.
Results:
One hundred ninety-two persons (33%) had a walking disability. This disability was highly associated with poor mobility in daily life, recurrent falls, and poor well-being (all P <.001). Of the common chronic diseases, stroke, angina pectoris, diabetes mellitus, and hip fracture but not arthritis contributed most (PARs from 6% to 15%) to walking disability in the population at large. General impairments had higher prevalence rates and higher PARs than common chronic diseases. Cognitive impairment, depressive symptoms, and dizziness upon rising contributed most (PARs between 22 to 27%) to walking disability. In multivariate regression analyses of all common chronic diseases and general impairments, associations remained significant.
Conclusion:
Within the general oldest-old population, general impairments contribute more substantially to walking disability than do common chronic diseases. The diagnosed diseases did not explain the impairments that led to walking disability. Especially in the oldest old, clinicians should focus not merely on common chronic diseases but particularly on general impairments as targets for diagnostic analysis and treatment to decrease walking disability.
Of 1042 individuals aged 65 years and over who were successfully interviewed in a community survey of health and physical activity, 35% (n=356) reported one or more falls in the preceding year. Although the overall ratio of female fallers to male fallers was 2.7: 1, this ratio approached unity with advancing age. Mobility was significantly impaired in those reporting falls. Asked to provide a reason for their falls, 53% reported tripping, 8% dizziness and 6% reported blackouts. A further 19% were unable to give a reason. There was no association between falls and the use of diuretics, antihypertensives or tranquillizers, but a significant association between falls and the use of hypnotics and antidepressants was found.
Discriminant analysis of selected medical and anthropometric variables indicated that handgrip strength in the dominant hand and reported symptoms of arthritis, giddiness and foot difficulties were most influential in predicting reports of recent falls.
The decline of strength with age has often been attributed to declining muscle mass in older subjects. To investigate factors
which might influence changes in strength across the life span, grip strength and muscle mass (as estimated by creatinine
excretion and forearm circumference) were measured in 847 healthy volunteers, aged 20—100 years, from the baltimore longitudinal
study of aging. Cross-sectional and longitudinal results concur that grip strength increases into the thirties and declines
at an accelerating rate after age 40. However, the grip strength of 48% of subjects less than 40 years old, 29% of individuals
40–59 years old, and 15% of subjects older than 60 did not decline during the average 9-year follow-up. Grip strength is strongly
correlated with muscle mass (r2 = .60, p < .0001). However, using multiple regression analysis, grip strength is more strongly correlated with age (partial r2 = .38) than muscle mass (partial r2 = .16). Additionally, a residuals analysis demonstrates that younger subjects are stronger and older subjects are weaker
than one would predict based on their muscular size. Thus, while strength losses are partially explained by declining muscle
mass, there remain other yet undetermined factors beyond declining muscle mass to explain some of the loss of strength seen
with aging
Falls are a leading cause of death from injury among older persons in the United States, and about one in three older persons falls each year. Yet, reliable estimates of the incidence of fall injury events in a population-based setting are not readily available. Therefore, the authors analyzed population-based surveillance data, between July 1985 and June 1987, from the Study to Assess Falls Among the Elderly, Miami Beach, Florida. The rate of fall injury events coming to acute medical attention increased exponentially with age for both elderly men and women (predominantly white), reaching a high for those aged 85 years or more of 138.5 per 1,000 for males and 158.8 per 1,000 for females. Compared with males, females had a higher incidence of fractures other than skull. Males were nearly twice as likely to die, however, following a fall injury event than were females. Of those fall injury events identified through the surveillance system, about 42% resulted in hospital admission. The mean length of hospital stay was 11.6 days overall and was 15.5 days for hip fracture, 9.8 days for skull fracture/intracranial injury, 11.2 days for all other fractures, and 9.1 days for all other injuries. About 50% of fall injury events that occurred at home and required hospital admission resulted in a person being discharged to a nursing home.
Serious fall injury represents a little studied, yet common and potentially preventable, cause of morbidity and mortality among older persons. We determined the frequency of, and risk factors for, experiencing serious fall injury events among older persons in the community.
A representative sample of 1103 community-living persons aged 72 years and older underwent comprehensive baseline and 1-year evaluations.
During a median 31 months of follow-up, fall data were obtained using fall calendars. Injury data were obtained from telephone interviews and from surveillance of emergency room and hospital records.
At least one fall was experienced by 546 (49%) participants. A total of 123 participants, representing 23% of fallers and 12% of the cohort, experienced 183 serious fall injury events. The factors independently associated with experiencing a serious injury during a fall included cognitive impairment (adjusted odds ratios 2.2; 95% confidence interval 1.5, 3.2); presence of at least two chronic conditions (2.0; 1.4, 2.9); balance and gait impairment (1.8; 1.3, 2.7); and low body mass index (1.8; 1.2, 2.5). In a separate analysis, including only subjects who fell, female gender (1.8; 1.1, 2.9) as well as most of the above factors were associated with experiencing a fall injury.
Several readily identifiable factors appeared to distinguish the subgroup of older fallers at risk for suffering a serious fall injury. These factors should help guide who and what to target in prevention efforts.
Muscle strength declines with advancing age; the causes of this are uncertain. In women, strength begins to decline around the time of menopause, suggesting that hormonal changes might influence strength. To determine the effect of postmenopausal estrogen use on muscle strength, neuromuscular function, and the risk of falling, we examined 9704 participants aged 65 years or more enrolled in the Study of Osteoporotic Fractures.
We measured hip abductor, triceps extensor, and hand-grip muscle strength, balance, gait speed, and self-reported functional disability. Falls during the first year of follow-up were determined from postcards that participants mailed every 4 months indicating whether they had fallen in the previous 4 months (> 99% complete follow-up).
After adjusting for age, medications, medical history, and personal habits, current estrogen users did not differ in a clinically meaningful way from those who had never used estrogen on tests of hip abductor strength (mean difference, 0.15 kg; 95% confidence interval, -0.05 to 0.34 kg), triceps extensor strength (0.005 kg; -0.17 to 0.18 kg), or grip strength (0.30 kg; 0.00 to 0.59 kg). Gait speed, time to stand five times from a chair, balance, self-reported disability, and incidence of falls (odds ratio, 1.12; 95% confidence interval, 0.87 to 1.44) also did not differ between current users and never users. In addition, current users were similar to past users on all measures.
We found no evidence that postmenopausal estrogen use has beneficial effects on muscle strength or neuromuscular function or that it reduces the risk of falling.
To determine the relation between estrogen replacement therapy and fractures.
Prospective cohort study.
Four clinical centers in Baltimore County, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania.
9704 ambulatory, nonblack women 65 years of age or older.
Estrogen use, medical history, and anthropometric data were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident fractures were validated by radiographic report.
After adjustment for potential confounders, current estrogen use was associated with a decrease in the risk for wrist fractures (relative risk [RR], 0.39; 95% CI, 0.24 to 0.64) and for all nonspinal fractures (RR, 0.66; CI, 0.54 to 0.80) when compared with no estrogen use. Results were similar for women using unopposed estrogen or estrogen plus progestin, for women younger or older than 75 years of age, and for current smokers or nonsmokers. The effect of estrogen remained after adjustment was made for appendicular bone mass. The relative risk for hip fracture tended to be lower among current users (RR, 0.60; CI, 0.36 to 1.02) than among never-users. Estrogen was most effective in preventing hip fracture among those older than 75 years. Current users who started estrogen within 5 years of menopause had a decreased risk for hip fractures (RR, 0.29; CI, 0.09 to 0.92), wrist fractures (RR, 0.29; CI, 0.13 to 0.68), and all nonspinal fractures (RR, 0.50; CI, 0.36 to 0.70) when compared with women who had never used estrogen. Previous use of estrogen for more than 10 years or use begun soon after menopause had no substantial effect on the risk for fractures.
Current use of estrogen appears to decrease the risk for fracture in older women. These results suggest that for protection against fractures, estrogen should be initiated soon after menopause and continued indefinitely.
Postural instability and falls in the elderly patient constitute a major health care problem. The etiology is often multifactorial, involving abnormal sensory input (visual, vestibular, and somatosensory), poor central processing, and suboptimal musculoskeletal biomechanics. Estrogen replacement therapy has been shown to prevent Alzheimer's disease and to improve cognitive performance in women with dementia. It was, therefore, postulated that estrogen replacement may improve central processing speed, which would result in improved postural stability. In this prospective, randomized, double-blinded study, 87 elderly female subjects (age > 69) were examined by repeated dynamic platform posturography, to measure the effect of estrogen therapy versus placebo upon postural stability. Results indicate that those receiving estrogen had no significant improvement in postural stability at 2 and 8 months of treatment relative to those receiving placebo. Trail Making B test was used as the psychometric test of central processing speed. There was no significant effect of estrogen on this measure over the 8 months of observations. It is concluded that 8 months of estrogen replacement therapy has no significant effect on central processing speed or postural stability in a healthy older female population.
To establish whether hormone replacement therapy affects postural balance in postmenopausal women.
Nineteen healthy postmenopausal women with vasomotor symptoms were included. Median age was 54 years, median time since menopause was 3 years. They underwent dynamic posturography before and after 4 and 12 weeks of transdermal estrogen treatment (17 beta-estradiol 50 micrograms/day) as well as after 2 additional weeks of combined estrogen-progestagen treatment. The dynamic posturography method quantifies the amplitude, frequency, and pattern of body sway and tests the visual, vestibular, and somatosensory systems, which together maintain balance. The two most difficult tests either cancel visual and distort somatosensory inputs or give distorted information from both the visual and somatosensory systems.
Hormone replacement therapy increased static balance performance assessed by dynamic posturography. A highly significant improvement was seen in the two most difficult tests between the pretreatment test and the test performed after 4 weeks of estrogen therapy (P < .01, P < .001, respectively). This improvement was sustained after 12 weeks and also during the 14th week, with the women on combined estrogen-progestagen treatment.
Estrogen treatment increased balance performance measured by dynamic posturography, indicating that the beneficial effects from estrogens on postmenopausal fracture risk may include central nervous system effects on balance. Two weeks' addition of gestagen to the treatment regimen did not counteract the estrogen effects.
The amount of bone mass and the tendency to fall are main risk factors for hip fractures and both deteriorate with advancing age. The dynamics between estrogen exposure and fracture protection seem too rapid to be explained by an effect on bone mass only. Postural balance function may be another potential mechanism for the fracture-protecting effect of estrogens.
We examined 16 long-term users of 17 beta-estradiol implants (20 mg) (mean age 67.9 years and mean duration of treatment 17.3 years [3.3 to 34 years]) and 16 age-matched (+/-2 years) nonusers (mean age 68.3 years). Postural balance (sway velocity) was measured by static posturography before and after blindfolding and application of vibration stimulus (20 to 100 Hz) to the calf muscles to disturb the proprioception and to induce imbalance.
Sway velocities were significantly lower in estrogen users than in nonusers (p = 0.0067) and similar to those in young premenopausal women. The differences were accentuated after provocation by blindfolding and by increasing frequencies of vibration stimulus to the calf muscle. Serum levels of estradiol and estradiol/sex hormone-binding globulin were negatively and follicle-stimulating hormone levels positively associated with sway velocity (p = 0.0194, p = 0.0036, and p = 0.0052, respectively) and independent of age (p = 0.02 to 0.005), supporting causality between estrogen exposure and postural balance.
These data indicate that postural balance function is better preserved in long-term estrogen users than in nonusers. Effects on postural balance function may be one mechanism explaining the rapid increase in distal forearm fractures early after menopause and the rapid dynamics between estrogen exposure and hip fracture protection and may potentially reduce the fracture risk in elderly women starting estrogen replacement therapy in spite of marginal increases in bone mass.
Although weight loss associated with human immunodeficiency virus (HIV) infection is multifactorial in its pathogenesis, it has been speculated that hypogonadism, a common occurrence in HIV disease, contributes to depletion of lean tissue and muscle dysfunction. We, therefore, examined the effects of testosterone replacement by means of Androderm, a permeation-enhanced, nongenital transdermal system, on lean body mass, body weight, muscle strength, health-related quality of life, and HIV-disease markers.
We randomly assigned 41 HIV-infected, ambulatory men, 18–60 yr of age, with serum testosterone levels below 400 ng/dL, to 1 of 2 treatment groups: group I, two placebo patches (n = 21); or group II, two testosterone patches designed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment.
Serum total and free testosterone and dihydrotestosterone levels increased, and LH and FSH levels decreased in the testosterone-treated, but not in the placebo-treated, men. Lean body mass and fat-free mass, measured by dual energy x-ray absorptiometry, increased significantly in men receiving testosterone patches [change in lean body mass,+ 1.345 ± 0.533 kg (P = 0.02 compared to no change); change in fat-free mass, +1.364 ± 0.525 kg (P = 0.02 compared to no change)], but did not change in the placebo group [change in lean body mass, 0.189 ± 0.470 kg (P = NS compared to no change); change in fat-free mass, 0.186 ± 0.470 kg (P = NS compared to no change)]. However, there was no significant difference between the 2 treatment groups in the change in lean body mass. The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels (r = 0.41; P = 0.02). The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches (P = 0.04). There was no significant change in body weight in either treatment group. Changes in overall quality of life scores did not correlate with testosterone treatment; however, in the subcategory of role limitation due to emotional problems, the men in the testosterone group improved an average of 43 points of a 0–100 possible score, whereas those in the placebo group did not change. Red cell count increased in the testosterone group (change in red cell count, +0.1 ± 0.1 1012/L) but decreased in the placebo group (change in red cell count, −0.2 ± 0.1 1012/L). CD4+ and CD8+ T cell counts and plasma HIV copy number did not significantly change during treatment. Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group.
Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment, an increased red cell count, and an improvement in role limitation due to emotional problems. Further studies are needed to assess whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men.
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.
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.
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.
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.
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.
The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index ofbioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.
To determine whether falling relates to serum levels of vitamin D and parathyroid hormone.
A cross-sectional study with retrospective analysis.
An aged-care institution in Melbourne Australia.
Ambulant nursing home and hostel residents (n = 83).
Frequency of falling, frequency of going outdoors, use of cane or walker, age, sex, weight, type of accommodation, and duration of residence. Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone (PTH). Plasma concentrations of albumin, calcium, phosphate, and creatinine. Use of furosemide or non-benzodiazepine anticonvulsants.
Median age of residents was 84 years. The cohort was vitamin D deficient with a median (interquartile range) 25-hydroxyvitamin D level of 27 (18-37) nmol/L (one-third the reference range median), P < .001. The median (interquartile range) PTH of 5.2 (3.8-7.7) pmol/L exceeded the reference range median, P < .001. Residents who fell (n = 33) had lower serum 25-hydroxyvitamin D levels than other residents (medians 22 vs 29 nmol/L, P = .02) and higher serum PTH levels (medians 6.2 vs 4.8 pmol/L, P < .01). Sixty residents lived in the hostel (72%), and 41 (49%) walked without any walking aid. In a multiple logistic regression for falling, higher serum PTH remained independently associated with falling, with an odds ratio (95% confidence interval) for falling of 5.6 (1.7-18.5) per unit of the natural logarithm of serum PTH. Other terms in the regression were hostel accommodation, odds ratio .04 (.01-.25), and ability to walk without aids, odds ratio .07 (.01-.37).
In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.
Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sexual function, increase in muscle mass and strength, and decrease in fat mass, with minimal adverse effects. We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range. We now report the effects of 180 days of treatment with this 1% T gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel, respectively) compared to those of a permeation-enhanced T patch (5 mg/day) on defined efficacy parameters in 227 hypogonadal men. In the T gel groups, the T dose was adjusted up or down to 75 mg/day (contained in 7.5 g gel) on day 90 if serum T concentrations were below or above the normal male range. No dose adjustment was made with the T patch group. Sexual function and mood changes were monitored by questionnaire, body composition was determined by dual energy x-ray absorptiometry, and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises. Sexual function and mood improved maximally on day 30 of treatment, without differences across groups, and showed no further improvement with continuation of treatment. Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment. Moderate increases were also observed in arm/chest muscle strength. At 90 days of treatment, lean body mass increased more in the 100 mg/day T gel group (2.74 +/- 0.28 kg; P = 0.0002) than in the 50 mg/day T gel (1.28 +/- 0.32 kg) and T patch groups (1.20 +/- 0.26 kg). Fat mass and percent fat were not significantly decreased in the T patch group, but showed decreases in the T gel groups (50 mg/day, -0.90 +/- 0.32 kg; 100 mg/day, - 1.05 +/- 0.22 kg). The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement. These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile. The increase in mean serum prostate-specific antigen levels (within the normal range) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group. Skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeation-enhanced T patch group. We conclude that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch.
The temporal relationship between depression and adverse functional outcomes in older adults is ambiguous. In the present eight-wave prospective community-based study, the longitudinal effect of depression on functional limitations and disability (in terms of disability days and bed days) was studied, thereby taking into account the role of chronic physical diseases.
The study is based on a sample which at the outset consisted of 325 non-depressed and 327 depressed persons (55-85 years) drawn from a larger random community based sample in the Netherlands. Generalized estimating equations time-lag models were used to examine the longitudinal relation between depression and both functional limitations and disability.
Functional limitations were very persistent over time, whereas disability days and bed days were more fluctuating functional outcomes. Only in the presence of chronic physical diseases, there was a significant longitudinal association between depression at the previous measurement and functional limitations, disability days and bed days at the next measurement. The effect on functional limitations was small, which was probably partly due to their persistent nature.
The finding of a longitudinal relationship between depression and functional outcomes in older adults with a compromised health status provides a rationale for treatment of chronic physical diseases as well as depression in depressed chronically ill elderly, in order to prevent a spiralling decline in psychological and physical health.
The purpose of this study was to examine the relationship between estrogen use and muscle strength, bone mineral density (BMD), and body composition variables in postmenopausal women. Forty healthy, untrained women participated in this study. Subjects (53-65 years) were > or =5 years postmenopausal and were categorized into either estrogen replacement therapy (ERT n=20) or non-estrogen replacement therapy (Non-ERT n=20) groups.
Muscular strength was measured by 1-RM testing using Cybex isotonic weight machines. Handgrip strength was measured using a handgrip dynamometer. Diagnostic Ultrasound was used to determine cross-sectional areas of the biceps brachii and rectus femoris muscle groups. BMD of the lumbar spine, proximal femur, and total body was assessed by Dual Energy X-Ray Absorptiometry (Lunar DPX-IQ). Body composition variables were obtained from the total body scan. Serum osteocalcin was measured as an indicator of bone remodeling.
There were no significant differences (P>0.05) for isotonic muscular strength, muscle cross-sectional areas, handgrip strength, or percent fat between ERT and Non-ERT groups. ERT had significantly higher (P<0.05) BMD for the total body, femoral neck and Ward's Area. There were moderate positive relationships between lean body mass and the hip sites (r=0.61-0.70, P<0.05). Regression analyses determined that lean body mass was the strongest predictor of the hip BMD sites. Estrogen use also was a significant predictor for the femoral neck and Ward's Area sites.
Women taking estrogen exhibited similar muscular strength, muscle size, and body composition as their estrogen-deficient counterparts. Estrogen use was also associated with higher BMD for the total body and hip sites. Generally, body composition, specifically lean body mass, influenced hip BMD more than muscular strength or estrogen use.
The role of estrogens in male physiology has become more evident, as a consequence of the discovery of human models of estrogen deficiency such as estrogen resistance or aromatase deficiency. In males, testosterone is the major source of plasma estradiol, the main biologically active estrogen, only 20% of which is secreted by the testes. Plasma estrone, 5% of which is converted to plasma estradiol, originates from tissue aromatization of, mainly adrenal, androstenedione. The plasma concentration of estradiol in males is 2-3 ng/dl and its production rate in blood is 25-40 micrograms/24 h; both of these values are significantly higher than in postmenopausal women. Plasma levels of estradiol do not necessarily reflect tissue-level activity as peripherally formed estradiol is partially metabolized in situ; thus, not all enters the general circulation, with a fraction remaining only locally active. Of the factors influencing plasma estradiol levels, plasma testosterone is a major determinant. However, the age-associated decrease in testosterone levels is scarcely reflected in plasma estradiol levels, as a result of increasing aromatase activity with age and the age-associated increase in fat mass. Free and bioavailable estradiol levels do decrease modestly with age as does the ratio of free testosterone to free estradiol, the latter testifying to the age-associated increased aromatization of testosterone. Estradiol levels are highly significantly positively related to body fat mass and more specifically to subcutaneous abdominal fat, but not to visceral (omental) fat. Indeed, aromatase activity in omental fat is only one-tenth of the activity in gluteal fat. Estrogens in males play an important role in the regulation of the gonadotropin feedback, several brain functions, bone maturation, regulation of bone resorption and in lipid metabolism. Moreover, they affect skin metabolism and are an important factor determining sex interest in man.
It is not clear which specific cognitive function is strongest related to falls. To investigate this, not only "general cognitive functioning," but also "nonverbal and abstract reasoning," "information processing speed," and "immediate memory" were related to falls. Furthermore, relevant effect modifiers, confounders, and mediators were identified. This study was performed within the Longitudinal Aging Study Amsterdam (LASA), a multidisciplinary, prospective cohort study. In this study (n = 1437), an interaction between "immediate memory" and age was found. In persons aged 75 years and over, "immediate memory," as measured by the 15 Words Test, showed to be an independent risk factor for falls. Part of this relationship was explained by the mediating effects of activity, mobility, and grip strength. The association between the other cognitive functions and falls was only statistically significant in univariate analysis. We conclude that "immediate memory" is an independent risk factor for recurrent falls in persons aged 75 years and older.
This study examined the association of (change in) physical activity and decline in mobility performance in older men and women.
A 3-year prospective study using data of the Longitudinal Aging Study.
Netherlands.
Two thousand one hundred nine men and women aged 55 to 85.
Total physical activity (expressed as hours per day and kilocalories per day) and sports participation were measured using a validated, interviewer-administered questionnaire. Mobility performance was assessed using two timed tests: 6-meter walk and repeated chair stands.
Mobility performance declined for 45.6% of the sample. At baseline, the mean time +/- standard deviation spent on total physical activity was 3.0 +/- 2.1 h/d or 719 +/- 543 kcal/d, and 56.6% of the sample participated in sports. Sports participation and a higher level of total physical activity, walking, or household activity were associated with a smaller mobility decline. After 3 years, total physical activity declined, and only 53.4% of those reporting sports at baseline continued doing so. Continuation of physical activity over time was associated with the smallest decline in mobility. The observed associations were similar for those with and without chronic disease (P> 0.3). The conclusions did not change after adjustment for potential confounders, including demographic and lifestyle variables, depression, and cognitive status.
Physical activity, and especially a regularly active lifestyle, may slow the decline in mobility performance. A beneficial effect was observed for sports and nonsports activities, independent of the presence of chronic disease.