"SARCOPENIA MEASURED BY ULTRASOUND IN HOSPITALIZED OLDER ADULTS" (ECOSARC): multi-centre, prospective observational study protocol.

BACKGROUND: Measurement of muscle mass and function, and thereafter, screening and diagnosis of sarcopenia, is a challenge and a need in hospitalized older adults. However, it is difficult in complex real-world old patients, because usually they are unable to collaborate with clinical, functional, and imaging testing. Ultrasound measurement of quadriceps rectus femoris (QRF) provides a non-invasive, real-time assessment of muscle quantity and quality, and is highly acceptable to participants with excellent inter-rater and intra-rater variability. However, normative data, protocol standardization, and association with longitudinal outcomes, needs further research and consensus. METHODS: Prospective exploratory multicenter study in older adults admitted to Acute Geriatric Units (AGUs) for medical reasons. 157 subjects from 7 AGUs of Spain were recruited between May 2019 and January 2022. Muscle ultrasound measurements of the anterior vastus of the QRF were acquired on admission and on discharge, using a previously validated protocol, using a Chieson model ECO2 ultrasound system (Chieson Medical Technologies, Co. Ltd, Wimxu District Wuxi, Jiangsu, China). Measurements included the cross-sectional area, muscle thickness in longitudinal view, intramuscular central tendon thickness, echogenicity, and the presence or absence of edema and fasciculations. Functional, nutritional, and DXA measurements were provided. Clinical follow-up was completed at discharge, and 30 and 90 days after discharge. Variations between hospital admission and discharge ultrasound values, and the relationship with clinical variables, will be analyzed using paired t-tests, Wilcoxon tests, or Mc Nemar chi-square tests when necessary. Prevalence of sarcopenia will be calculated, as well as sensitivity and specificity of ultrasound measurements to determine sarcopenia. Kappa analysis will be used to analyze the concordance between measurements, and sensitivity analysis will be conducted for each participating center. DISCUSSION: The results obtained will be of great interest to the scientific geriatric community to assess the utility and validity of ultrasound measurements for the detection and follow-up of sarcopenia in hospitalized older adults, and its association with adverse outcomes. TRIAL REGISTRATION: NCT05113758. Registration date: November 9th 2021. Retrospectively registered.

[The European ADVANTAGE experience for management of frailty: keys to its applicability in Latin AmericaA experiência europeia ADVANTAGE para manejo da fragilidade: apontamentos para sua aplicabilidade na América Latina]. / La experiencia europea ADVANTAGE para el manejo de la fragilidad: claves sobre su aplicabilidad en América Latina.

The European Commission and 22 of its Member States cofinanced, in 2017-2019, the first joint action to address frailty in older persons, known as ADVANTAGE Joint Action. The initiative developed a common strategy, based on the best scientific evidence, to position healthy aging and frailty as priority public health issues in the participating countries and thus contribute to uniformly addressing frailty across Europe. This article details the methodology and main achievements of ADVANTAGE and includes an analysis of the key factors contributing to its success. In the Action's three years, powerful multisectoral networks were formed and developed, both nationally and internationally. ADVANTAGE succeeded in mapping out practical routes for comprehensively addressing frailty and dependency prevention in 22 countries with very heterogeneous political, economic, social, and organizational realities. ADVANTAGE has demonstrated that actions of this type are feasible and effective, and that if the key points of success that have been identified are considered and applied, duly adjusted to each reality, this action can be replicable in any country resolved to promoting the healthy aging of its population, including those of Latin America and the Caribbean.

De 2017 a 2019, a Comissão Europeia e 22 dos seus Estados Membros cofinanciaram a primeira ação conjunta para abordar a fragilidade em idosos, denominada ADVANTAGE Joint Action. No âmbito dessa iniciativa, foi definida uma estratégia comum, baseada nas melhores evidências científicas, para posicionar o envelhecimento saudável e a fragilidade como questões prioritárias de saúde pública nos países participantes, contribuindo, assim, para uma abordagem homogênea à fragilidade em toda a Europa. Este artigo detalha a metodologia do trabalho realizado e as principais conquistas da ADVANTAGE, e inclui uma análise das chaves que contribuíram para seu sucesso. Nos três anos de operação da iniciativa, foram formadas e desenvolvidas poderosas redes multissetoriais, tanto nacional quanto internacionalmente. A iniciativa ADVANTAGE foi capaz de criar roteiros práticos para abordar de maneira global a fragilidade e a prevenção da dependência em 22 países com realidades políticas, econômicas, sociais e organizacionais bastante heterogêneas. A ADVANTAGE mostrou que ações deste tipo são viáveis e eficazes, e que se os principais fatores de sucesso identificados forem levados em consideração e aplicados, devidamente ajustados a cada realidade, esta ação pode ser reproduzida em qualquer país determinado a promover o envelhecimento saudável de sua população, inclusive na América Latina e no Caribe.

Muscle mass loss measured with portable ultrasound in hospitalized older adults: The ECOSARC study.

OBJECTIVES: The main objective was to analyze the evolution of muscle of the Quadriceps Rectus Femoris (QRF) between admission and discharge, in older adults hospitalized with an acute medical disease in Acute Geriatric Units (AGUs). DESIGN: Prospective multicentric observational cohort study. SETTING: Seven AGUs from University Hospitals in Spain. PARTICIPANTS: Hospitalized adults ≥ 70 years old, able to ambulate and without severe dementia. MEASUREMENTS: Ultrasound measurements of QRF were acquired at 2/3 distal between anterior-superior iliac spine and patella in both legs by trained Geriatricians. Ultrasound Chison model ECO2 was used. QRF area, thickness, edema, echogenicity, and fasciculations were measured. RESULTS: From the complete sample (n = 143), in 45 (31.5%) participants, ultrasound images were classified as non-valid by an expert radiologist. Mean age was 87.8 (SD 5.4). Mean hospital stay 7.6 days (SD 4.3). From those with valid images, 36 (49.3%), 2 (2.7%), and 35 (47.9%) presented a decrease, equal values, or an increase in QRF area from baseline to discharge, respectively, and 37 (50.0%), 2 (2.7%), and 35 (47.3%) presented a decrease, equal values, or an increase in QRF thickness, respectively. 26 (35.6%) presented a decrease in more than 0.2 cm2 of QRF area, and 23 (31.1%) a decrease in more than 0.1 cm of QRF thickness. Only 4 (5.4%) patients presented new edema, while 13 (17.6%) worsened echogenicity. CONCLUSION: One third of older adults develop significant muscle loss during a hospitalization for acute medical diseases. TRIAL REGISTRATION NUMBER: NCT05113758.

[Acute postoperative confusional syndrome in the elderly patient]. / Síndrome confusional agudo postoperatorio en el paciente anciano.

With the progressive aging of the population surgical candidates have more comorbidities resulting in a higher risk to develop postoperative complications. One of the most frequent postoperative complications in the elderly is acute confusional state or delirium, which may have devastating consequences: higher mortality, and risk of medical complications during admission and, a higher risk of functional decline, institutionalization, and cognitive impairment at discharge. For all these reasons and with the aim of optimising surgical procedures, it is essential to identify patients at risk of delirium in order to take appropriate preventive action and provide early treatment. In the present article we review the current evidence on the management of postoperative delirium in the elderly.

Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.

BACKGROUND: The association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one-off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels. METHODS: Participants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow-up (median 5.04 years) were used to construct frailty trajectories according to group-based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital. RESULTS: Nine hundred and seventy-five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non-frailty (WNF), improving to non-frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21-3.32]; RF = 1.92 [1.18-3.12]; IF = 2.67 [1.48-4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11-3.82); RF = 2.29 (1.30-4.03); IF = 3.55 (1.37-9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19-3.76); RF = 2.14 (1.26-3.64); IF = 2.21 (1.06-4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose-response relationship between baseline FTS5 score and adverse events. CONCLUSIONS: Belonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.

Role of sarcopenia in the frailty transitions in older adults: a population-based cohort study.

BACKGROUND: Frailty and sarcopenia are age-associated syndromes that have been associated with the risk of several adverse events, mainly functional decline and death, that usually coexist. However, the potential role of one of them (sarcopenia) in modulating some of those adverse events associated to the other one (frailty) has not been explored. The aim of this work is to assess the role of sarcopenia within the frailty transitions and mortality in older people. METHODS: Data from the Toledo Study of Healthy Aging (TSHA) were used. TSHA is a cohort of community-dwelling older adults ≥65. Frailty was assessed according with the Frailty Phenotype (FP) and the Frailty Trait Scale-5 (FTS5) at baseline and at follow-up. Basal sarcopenia status was measured with the standardized Foundation for the National Institutes of Health criteria. Fisher's exact test and logistic regression model were used to determine if sarcopenia modified the transition of frailty states (median follow-up of 2.99 years) and Cox proportional hazard model was used for assessing mortality. RESULTS: There were 1538 participants (74.73 ± 5.73; 45.51% men) included. Transitions from robustness to prefrailty and frailty according to FP were more frequent in sarcopenic than in non-sarcopenic participants (32.37% vs. 15.18%, P ≤ 0.001; 5.76% vs. 1.12%; P ≤ 0.001, respectively) and from prefrailty-to-frailty (12.68% vs. 4.27%; P = 0.0026). Improvement from prefrail-to-robust and remaining robust was more frequent in non-sarcopenic participants (52.56% vs. 33.80%, P ≤ 0.001; 80.18% vs 61.15%, P ≤ 0.001, respectively). When classified by FTS5, this was also the case for the transition from non-frail-to-frail (25.91% vs. 4.47%, P ≤ 0.001) and for remaining stable as non-frail (91.25% vs. 70.98%, P ≤ 0.001). Sarcopenia was associated with an increased risk of progression from robustness-to-prefrailty [odds ratio (OR) 2.34 (95% confidence interval, CI) (1.51, 3.63); P ≤ 0.001], from prefrailty-to-frailty [OR(95% CI) 2.50 (1.08, 5.79); P = 0.033] (FP), and from non-frail-to-frail [OR(95% CI) 4.73 (2.94, 7.62); P-value ≤ 0.001]. Sarcopenia does not seem to modify the risk of death associated with a poor frailty status (hazard ratios (HR, 95%) P > 0.05). CONCLUSIONS: Transitions within frailty status, but not the risk of death associated to frailty, are modulated by the presence of sarcopenia.

[Advantage, a joint action to face up to frailty.] / Advantage, una acción conjunta para plantarle cara a la fragilidad.

The European Commission and 22 European Union Member States cofounded the first Joint Action (JA) in frailty: ADVANTAGE. It aimed to build a common framework to push frailty as a public health priority contributing to a homogeneous and evidence-based approach across Europe. This article details how the JA has evolved and its main results, especially in Spain where the Roadmap to Approach Frailty was developed within the Strategy of Health Promotion and Prevention of the National Health System and approved by the Public Health Commission on 14/11/2019. This document includes six actions to be implemented in the coming years.

La Comisión Europea ha cofinanciado, junto 22 estados miembros de la Unión Europea, la primera Acción Conjunta en fragilidad: ADVANTAGE. Su objetivo ha sido definir una estrategia común que posicionase la fragilidad como tema prioritario de salud pública y que contribuyese a impulsar su abordaje, basado en evidencias, de una manera más homogénea en Europa. En este artículo se detalla cómo se desarrolló la acción y cuáles fueron los principales resultados, especialmente en España, donde, en el marco de la Estrategia de Promoción de la Salud y Prevención en el SNS, se elaboró la Hoja de ruta para el abordaje de la fragilidad en España que fue aprobada por la Comisión de Salud Pública el 14/11/2019. Este documento incluye seis acciones a desarrollar en los próximos años.

[Effectiveness of reevaluation of admission of patients with poor functional status]. / Efectividad de la revaloración de ingresos de pacientes con mala situación funcional.

INTRODUCTION: Acute care hospitals are one of the healthcare settings that pose the greatest risk of inefficiency and iatrogeny in the elderly. The term "inappropriate admission" refers to those admissions that could have been dealt with in an outpatient clinic or in a hospital with a lower level of care. We designed an intervention in the Emergency Department of our hospital (Hospital Universitario de Getafe, Madrid) with the aim of reducing the percentage of inappropriate admissions in the elderly. MATERIAL AND METHOD: A geriatrician reevaluated admissions of patients aged 75 years old and above, with established severe dependence in either of the two areas evaluated (physical and cognitive) and who were candidates for admission to the Acute Unit. RESULTS: Of 380 patients who were reevaluated, 240 were discharged instead of being admitted. These patients were referred to different levels of care: 123 patients (51.25%) were monitored in the Community Care Unit, 12 (5%) were referred to other hospitals with a lower level of care (Palliative Unit and/or Long Term care Unit) and 8 patients (3.34%) were sent to the outpatient clinic. By avoiding 240 admissions, an estimated 1992 stays were prevented, representing a saving of 619, 512 euros. CONCLUSION: Assessment of elderly patients by geriatricians in the Emergency Department and the availability of distinct levels of care are effective resources to avoid inappropriate admissions.

The Standardization of Frailty Phenotype Criteria Improves Its Predictive Ability: The Toledo Study for Healthy Aging.

INTRODUCTION: Several studies have assessed the performance of the original frailty phenotype criteria (FPC) and the standardized version according to the characteristics of the population. No studies exist, however, evaluating the impact of this standardization on its predictive ability. OBJECTIVE: To compare how the original FPC and the standardized-frailty phenotype criteria (S-FPC) estimate the prevalence of frailty and their ability to predict mortality, hospitalization, incident disability, and falls. METHODS: Data were taken from the Toledo Study for Healthy Aging, a population-based, community-dwelling study conducted on 1645 individuals over 65. Frailty was operationalized in two ways: FPC, using the cut-off estimated in the Cardiovascular Health Study and S-FPC, using cut-off points fitted to the phenotypic characteristics of our study sample. Frailty prevalences were compared using chi-square statistic. Cox proportional hazard models and logistic regressions evaluated the predictive ability of both tools. Lastly, survival tests were applied. RESULTS: Frailty and prefrailty prevalences varied according to the tool used: 24.12% and 66.40%, respectively when we used FPC and 6.68% and 47.81% when we used S-FPC (P < .01). Regarding their predictive ability, S-FPC, but not FPC, identified consistently the prefrail persons as an intermediate risk group between robust and frail people [death 1.57 (1.15-2.16); hospitalization 1.47 (1.16-1.85); and incident disability 1.96 (1.30-2.97); P < .005]. Furthermore S-FPC predicted death and hospitalization at shorter times than FPC (P < .05). CONCLUSION: FPC should be standardized according to the characteristics of the population in order to improve its predictive ability.

La experiencia europea ADVANTAGE para el manejo de la fragilidad: claves sobre su aplicabilidad en América Latina

[RESUMEN]. La Comisión Europea y 22 de sus Estados Miembros cofinanciaron durante 2017-2019 la primera acción con-junta para abordar la fragilidad en las personas mayores, denominada ADVANTAGE Joint Action. En el marco de esta iniciativa, se definió una estrategia común, basada en la mejor evidencia científica, para posicionar el envejecimiento saludable y la fragilidad como temas prioritarios de salud pública en los países participantes y contribuir así a un abordaje homogéneo de la fragilidad en toda Europa. En este artículo se detalla la metodo-logía del trabajo realizado y los principales logros de ADVANTAGE y se incluye un análisis de las claves que contribuyeron a su éxito. En los tres años de funcionamiento se formaron y desarrollaron potentes redes de tra-bajo multisectoriales, tanto a nivel nacional como internacional. ADVANTAGE logró marcar rutas prácticas para abordar de manera global la fragilidad y la prevención de la dependencia en 22 países con realidades políticas, económicas, sociales y organizativas muy heterogéneas. ADVANTAGE ha demostrado que acciones de este tipo son factibles y eficaces, y que si se toman en cuenta y aplican los puntos clave de éxito identificados, debi-damente ajustados a cada realidad, esta acción puede ser reproducible en cualquier país decidido a promover el envejecimiento saludable de su población, incluidos los de América Latina y el Caribe.

[ABSTRACT]. The European Commission and 22 of its Member States cofinanced, in 2017-2019, the first joint action to address frailty in older persons, known as ADVANTAGE Joint Action. The initiative developed a common strategy, based on the best scientific evidence, to position healthy aging and frailty as priority public health issues in the participating countries and thus contribute to uniformly addressing frailty across Europe. This article details the methodology and main achievements of ADVANTAGE and includes an analysis of the key factors contributing to its success. In the Action’s three years, powerful multisectoral networks were formed and developed, both nationally and internationally. ADVANTAGE succeeded in mapping out practical routes for comprehensively addressing frailty and dependency prevention in 22 countries with very heterogeneous political, economic, social, and organizational realities. ADVANTAGE has demonstrated that actions of this type are feasible and effective, and that if the key points of success that have been identified are considered and applied, duly adjusted to each reality, this action can be replicable in any country resolved to promoting the healthy aging of its population, including those of Latin America and the Caribbean.

[RESUMO]. De 2017 a 2019, a Comissão Europeia e 22 dos seus Estados Membros cofinanciaram a primeira ação con-junta para abordar a fragilidade em idosos, denominada ADVANTAGE Joint Action. No âmbito dessa iniciativa, foi definida uma estratégia comum, baseada nas melhores evidências científicas, para posicionar o envel-hecimento saudável e a fragilidade como questões prioritárias de saúde pública nos países participantes, contribuindo, assim, para uma abordagem homogênea à fragilidade em toda a Europa. Este artigo detalha a metodologia do trabalho realizado e as principais conquistas da ADVANTAGE, e inclui uma análise das chaves que contribuíram para seu sucesso. Nos três anos de operação da iniciativa, foram formadas e desen-volvidas poderosas redes multissetoriais, tanto nacional quanto internacionalmente. A iniciativa ADVANTAGE foi capaz de criar roteiros práticos para abordar de maneira global a fragilidade e a prevenção da dependên-cia em 22 países com realidades políticas, econômicas, sociais e organizacionais bastante heterogêneas. A ADVANTAGE mostrou que ações deste tipo são viáveis e eficazes, e que se os principais fatores de sucesso identificados forem levados em consideração e aplicados, devidamente ajustados a cada realidade, esta ação pode ser reproduzida em qualquer país determinado a promover o envelhecimento saudável de sua população, inclusive na América Latina e no Caribe.

Obesity, fat distribution, and risk of frailty in two population-based cohorts of older adults in Spain.

OBJECTIVE: To evaluate for the first time the longitudinal relationship between abdominal obesity and the onset of frailty. METHODS: Study based on results from two population-based cohorts, the Seniors-ENRICA, with 1801 individuals aged ≥60, and the Toledo Study for Healthy Ageing (TSHA), with 1289 participants ≥65 years. Incident frailty was assessed with the Fried criteria. RESULTS: During 3.5 years of follow-up, 125 individuals with incident frailty in Seniors-ENRICA and 162 in TSHA were identified. After adjustment for the main confounders, the pooled odds ratio (pooled OR) for general obesity and risk of frailty was 1.73 (95% confidence interval [CI]: 1.18-2.28). Abdominal obesity was also associated with frailty (pooled OR: 1.67; 95% CI: 1.09-2.25). Compared with individuals with BMI <25 kg/m(2) and no abdominal obesity, the risk of frailty was highest among individuals with concurrent general and abdominal obesity (pooled OR: 2.55; 95% CI: 1.23-3.86). General obesity was associated with increased risk of exhaustion (pooled OR: 1.66; 95% CI: 1.11-2.21), low physical activity (pooled OR: 1.57; 95% CI: 1.08-2.05), and weakness (pooled OR: 1.63; 95% CI: 1.12-2.05). For abdominal obesity, results were in the same direction, although they showed statistical significance only for weakness (OR: 1.46; 95% CI: 1.11-1.80). CONCLUSIONS: General and abdominal obesity are associated with incident frailty in the elderly.

Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging.

Cardiovascular disease (CVD), both clinical and subclinical, has been proposed as one of the mechanisms underlying frailty. However, there is no evidence addressing the relationship between the earliest stage of CVD (endothelial dysfunction) and frailty. The goal of the study was to analyze the association between endothelial dysfunction, evaluated by asymmetric dimethylarginine (ADMA) levels, and frailty. We used data from the Toledo Study for Healthy Aging, a prospective Spanish cohort study. Biological samples were obtained and ADMA levels were determined using an enzyme immunoassay method. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals of frailty associated with ADMA. Adjustments were made for age, gender, cardiovascular risk factors, and presence of atherosclerotic disease (assessed by ankle­brachial index; ABI). One thousand two hundred eighty-seven community-dwelling elderly were included. One hundred seven (8.3 %) were identified as frail, 542 (42.1 %) as pre-frail, and 638 (49.6 %) as non-frail. ADMAvalues were higher in frail subjects than in non-frail ones. In addition, an interaction between the presence of atherosclerotic disease and ADMA on the odds of frailty (p=0.045) was detected. After adjustments for age, classical cardiovascular risk factors, and ABI, the risk of frailty was associated with increasing levels of ADMA in subjects without atherosclerotic disease [OR for 1 standard deviation increase in ADMA=1.14 (1.01­1.28), p=0.032] but not in those with atherosclerotic disease. In our study, endothelial dysfunction, assessed by ADMA levels, is associated with frailty. These findings provide additional support for a relevant role of vascular system since its earliest stage in frailty.

Age and gender, two key factors in the associations between physical activity and strength during the ageing process.

OBJECTIVES: The aims of this study were to identify if the associations of physical activity (PA) and muscle strength may vary throughout the ageing process; to study the differences among genders in the relationships between PA and strength in elderly people and to test whether these differences are explained by the hormonal, nutritional and inflammatory status. STUDY DESIGN: A total of 1741 people ≥65 years of age participated in this cross-sectional study. MAIN OUTCOME MEASURES: Upper- and lower-limbs maximal voluntary isometric strength was obtained using standardized techniques and equipment. PA was recorded by a validated questionnaire. The associations of PA with strength were assessed using generalized linear regression models with a Gamma-distributed dependent variable. RESULTS: A significant gender by PA interaction was found for all strength-related variables (all P<0.01). Moreover, when sexual hormones, albumin or C-Reactive protein were taken into account in the model, the results did not significantly change. In women, PA was positively associated with upper and lower-body strength; however in men, PA was only associated with grip and knee strength (both P<0.01). Higher strength values were associated with higher levels of PA, especially in women. However, this tendency had a different pattern across the age range, showing a stronger association in the 'young' elderly compared with the 'old' elderly. CONCLUSION: Higher levels of PA are related to greater muscle strength, especially in women and those who were younger.

Sex differences in the association between serum levels of testosterone and frailty in an elderly population: the Toledo Study for Healthy Aging.

BACKGROUND: Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. METHODS: We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. RESULTS: In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. CONCLUSION: There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved.