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      Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging

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          Abstract

          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.

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          Most cited references30

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          Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.

          We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally. Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10-15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends. The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.
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            Frailty in older adults: evidence for a phenotype

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              Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study.

              Physical frailty is associated with reduced muscle strength, impaired physical function, and quality of life. Testosterone (T) increases muscle mass and strength in hypogonadal patients. It is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T. Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men, on muscle mass and strength, physical function, and quality of life. We conducted a randomized, double-blind, placebo-controlled, parallel-group, single-center study. PARTICIPANTS were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter. Two hundred seventy-four participants were randomized to transdermal T (50 mg/d) or placebo gel for 6 months. Outcome measures included muscle strength, lean and fat mass, physical function, and self-reported quality of life. Isometric knee extension peak torque improved in the T group (vs. placebo at 6 months), adjusted difference was 8.6 (95% confidence interval, 1.3-16.0; P = 0.02) Newton-meters. Lean body mass increased and fat mass decreased significantly in the T group by 1.08 +/- 1.8 and 0.9 +/- 1.6 kg, respectively. Physical function improved among older and frailer men. Somatic and sexual symptom scores decreased with T treatment; adjusted difference was -1.2 (-2.4 to -0.04) and -1.3 (-2.5 to -0.2), respectively. T treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition, quality of life, and physical function. Further investigations are warranted to extend these results.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                5 March 2012
                : 7
                : 3
                : e32401
                Affiliations
                [1 ]Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Madrid, Spain
                [2 ]Servicio de Análisis Clinicos, Hospital Universitario de Getafe, Madrid, Spain
                [3 ]Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, Spain
                [4 ]Servicio de Geriatría, Hospital Virgen del Valle, Complejo Hospitalario de Toledo, Toledo, Spain
                University of Valencia, Spain
                Author notes

                Conceived and designed the experiments: LRM FGG AAA. Performed the experiments: CB. Analyzed the data: LC CAB AAA LRM. Wrote the paper: LC LRM.

                Article
                PONE-D-11-24400
                10.1371/journal.pone.0032401
                3293806
                22403651
                bf64f6f8-42c7-4893-afbc-d5f04f947801
                Carcaillon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 7 December 2011
                : 30 January 2012
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Physiological Processes
                Medicine
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Endocrinology
                Endocrine Physiology
                Epidemiology
                Geriatrics

                Uncategorized
                Uncategorized

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