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Sarcopenia/Frailty

Discussion in 'Men's Health Forum' started by Michael Scally MD, Jul 14, 2017.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    McKee A, Morley JE, Matsumoto AM, Vinik A. Sarcopenia: an Endocrine Disorder? Endocr Pract. http://journals.aace.com/doi/10.4158/EP171795.RA?code=aace-site

    Sarcopenia is defined as low muscle function (walking speed or grip strength) in the presence of low muscle mass. A simple screening test - the SARC-F - is available to identify persons with sarcopenia. The major endocrine causes of sarcopenia are diabetes mellitus and male hypogonadism.

    Other causes are decreased physical activity, loss of motor neuron units, weight loss, inflammatory cytokines, reduced blood flow to muscles, very low 25(OH) vitamin D levels and decreased growth hormone and igf-1.

    Treatment for sarcopenia includes resistance and aerobic exercise, leucine enriched essential amino acids, and vitamin D. In hypogonadal males, testosterone improves muscle mass, strength and function. Selective androgen receptor molecules and antimyostatin activin II receptor molecules are under development as possible treatments for sarcopenia.
     

    Attached Files:

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  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Muscle Wasting and Sarcopenia in Heart Failure and Beyond

    Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure.

    However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training.

    Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, igf-1, compounds targeting myostatin signaling, which have their own set of side effects.

    There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one.

    Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017. ESC Heart Fail 2017;4(4):492-8. Muscle wasting and sarcopenia in heart failure and beyond: update 2017
     
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Swiecicka A, Eendebak R, Lunt M, et al. Reproductive hormone levels predict changes in frailty status in community-dwelling older men: European Male Ageing Study prospective data. J Clin Endocrinol Metab 2017. https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.2017-01172/4657090

    Context: Clinical sequelae of androgen deficiency share common features with frailty. Evidence supporting the role of androgens in the development of frailty is limited and conflicting.

    Objective: To determine associations between male reproductive hormones and prospective changes in frailty status. Design/ Setting: 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study.

    Participants: 3369 men aged 40-79 from 8 European centres. Intervention: nil.

    Main Outcome Measure: Frailty status was determined using frailty index (FI n=2278) and frailty phenotype (FP, n=1980).

    Results: After adjusting for baseline frailty, age, centre and smoking, the risk of worsening FI decreased with higher testosterone (T), free T and dihydrotestosterone (DHT) [% change (95%CI) in FI associated with 1SD higher hormone level: -3.0 (-5.9, -1.0) for total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) for DHT]. After further adjustment for BMI, only free T remained a significant predictor of FI change. In fully adjusted models, higher LH and FSH were positively related to worsening FI only in men <60 years and higher estradiol predicted lower likelihood of improving FP [OR 0.68 (0.52, 0.88)].

    Conclusions: These prospective data support the hypothesis that higher androgen levels may protect elderly men from worsening frailty. However, the causal nature of these relationships requires further investigation. Whereas raised gonadotropins in men <60 yr might be an early marker of frailty, the role of estradiol in frailty needs further clarification.
     
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Therapist-Assisted Progressive Resistance Training, Protein Supplements, and testosterone Injections in Frail Older Men with Testosterone Deficiency: Protocol for a Randomized Placebo-Controlled Trial

    BACKGROUND: Fall accidents are a major cause of mortality among the elderly and the leading cause of traumatic brain injury. After a fall, many elderly people never completely recover and need help in coping with everyday life. Due to the increasing older population in the world, injuries, disabilities, and deaths caused by falls are a growing worldwide problem.

    Muscle weakness leads to greatly increased risk of falling, decreased quality of life, and decline in functional capacity. Muscle mass and muscle power decrease about 40% from age 20 to 80 years, and the level of testosterone decreases with age and leads to impaired muscle mass. In addition, 20% of men older than 60 years-and 50% older than 80 years-have low levels of testosterone.

    Treatments after a fall are significant financial burdens on health and social care, and it is important to find treatments that can enhance function in the elderly people.

    OBJECTIVE: The purpose of this study is to investigate whether testosterone and progressive resistance training alone or combined can improve muscle strength and reduce the risk of falls in older men. Additionally, we will examine whether such treatments can improve quality of life, functional capacity, including sexual function, and counteract depression.

    METHODS: This is a randomized placebo-controlled, double-blind trial in which frail older men with testosterone deficiency are treated with testosterone supplemental therapy and therapist-assisted progressive resistance training for 20 weeks, with the possibility to continue treatment for 1 year. Four study arms of 48 participants each are provided based on factorial assignment to testosterone supplemental therapy and progressive resistance training.

    The 4 groups are as follows:
    · controls given placebo injections without physical exercise for 20 weeks,
    · testosterone-alone group given testosterone injections without physical exercise for 20 weeks,
    · training-alone group given placebo injections for 20 weeks combined with 16 weeks of progressive strength training, and
    · combination group given testosterone injections for 20 weeks combined with 16 weeks of progressive strength training.

    Performance in the 30-second chair stand test to measure improvement of general strength, balance, and power in lower extremities is the primary endpoint. Secondary endpoints comprising tests of cognition, muscle strength, and quality of life are applied before and after the training.

    RESULTS: Funding was provided in October 2016. Results are expected to be available in 2020. Sample size was calculated to 152 participants divided into 4 equal-sized groups. Due to age, difficulty in transport, and the time-consuming intervention, up to 25% dropouts are expected; thus, we aim to include at least 192 participants.

    CONCLUSIONS: This investigation will evaluate the efficacy of testosterone supplemental therapy alone or combined with progressive resistance training. Additionally, improvements in quality of life and cognition are explored.

    TRIAL REGISTRATION: Clinicaltrials.gov NCT02873559; Effect of PROGRESSive Training and Teststerone in Older Frail Men - Full Text View - ClinicalTrials.gov

    Rasmussen R, Midttun M, Kolenda T, et al. Therapist-Assisted Progressive Resistance Training, Protein Supplements, and Testosterone Injections in Frail Older Men with Testosterone Deficiency: Protocol for a Randomized Placebo-Controlled Trial. JMIR research protocols 2018;7:e71. https://www.researchprotocols.org/2018/3/e71/
     
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  5. Old

    Old Member

    Have heard of doctors treating HIV patients with steroids for muscle wasting BEFORE they have wasting. Then the doc gets in trouble.

    Doing so seems to help them. It is called PREVENTIVE medicine which is better than breakdown treatment.

    Treating early with androgens should apply to all as a need begins to become apparent, not waiting until they are frail and bones are brittle. The change last year of the reference range for testosterone is not based on science but rather political motives.
     
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Muscle Wasting Diseases: Novel Targets and Treatments

    Adequate skeletal muscle plasticity is an essential element for our well-being, and compromised muscle function can drastically affect quality of life, morbidity, and mortality.

    Surprisingly, however, skeletal muscle remains one of the most under-medicated organs. Interventions in muscle diseases are scarce, not only in neuromuscular dystrophies, but also in highly prevalent secondary wasting pathologies such as sarcopenia and cachexia.

    Even in other diseases that exhibit a well-established risk correlation of muscle dysfunction due to a sedentary lifestyle, such as type 2 diabetes or cardiovascular pathologies, current treatments are mostly targeted on non-muscle tissues.

    In recent years, a renewed focus on skeletal muscle has led to the discovery of various novel drug targets and the design of new pharmacological approaches.

    This review provides an overview of the current knowledge of the key mechanisms involved in muscle wasting conditions and novel pharmacological avenues that could ameliorate muscle diseases.

    Furrer R, Handschin C. Muscle Wasting Diseases: Novel Targets and Treatments. Annual Review of Pharmacology and Toxicology 2018. https://doi.org/10.1146/annurev-pharmtox-010818-021041

    Capture.PNG

    Signaling pathways involved in secondary muscle wasting, and potential drugs to reduce loss of muscle mass. Several classes of drugs are tested in clinical trials aimed at either inhibiting catabolic signaling, thereby reducing protein degradation (orange), or stimulating anabolic pathways and thereby increasing protein synthesis (blue).

    Activation via igf-1 or other upstream signals such as GH, androgens, or β2-agonist stimulates the PI3K-Akt-mTOR pathway, and as a consequence, protein synthesis is increased. In addition, Akt suppresses protein degradation by phosphorylating FoxO, thereby reducing its transcriptional activity.

    Several catabolic pathways contribute to muscle atrophy by increasing expression of the E3 ligases MAFbx and MuRF1 via the transcription factors FoxO, TFEB, or NF-κB, which all stimulate protein degradation, and by inhibiting PI3K-Akt-mTOR signaling and thereby reducing protein synthesis.

    MSTN acts as a major negative regulator of muscle mass by inhibiting Akt signaling.

    The multifactorial nature of secondary muscle wasting and the different signaling pathways involved in muscle atrophy aggravate the development of effective drugs.

    Abbreviations: FoxO, forkhead box O; GC, glucocorticoid; GH, growth hormone; IGF-1, insulin-like growth factor 1; MAFbx, muscle atrophy F-box protein; MSTN, myostatin; mTOR, mammalian target of rapamycin; MuRF1, muscle RING finger-containing protein 1; NF-κB, nuclear factor κB; T, testosterone.
     

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  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    The Stair Climb Power Test as an Efficacy Outcome in Randomized Trials of Function Promoting [Anabolic] Therapies

    Background - Standardization of performance-based physical function measures that are reliable and responsive to intervention is necessary for efficacy trials of function promoting anabolic therapies (FPTs).

    Herein, we describe a standardized method of measuring stair climbing power (SCP) and evaluate its ability to assess improvements in physical function in response to an FPT (testosterone) compared to gait speed.

    Methods - We used a 12-step SCP test with and without carrying a load (loaded, LSCP or unloaded, USCP) in two testosterone trials in older men. SCP was determined from mass, total step-rise, and time of ascent measured with an electronic timing system.

    Associations between SCP and leg press performance (strength and power), testosterone levels, and gait speed were assessed. Test–retest reliability was evaluated using interclass correlation and Bland–Altman analyses.

    Results - Baseline SCP was negatively associated with age and positively with leg strength and power and gait speed. Both tests of SCP were safe and showed excellent reliability (intra-class correlation 0.91–0.97 in both cohorts).

    Changes in testosterone concentrations were associated with changes in USCP and LSCP, but not gait speed in mobility-limited men. Changes in leg press performance were associated with SCP in both trials.

    Conclusions - Both USCP and LSCP are safe and have high test–retest reliability. Compared to gait speed, SCP is associated more robustly with leg press performance and is sensitive to testosterone therapy. The LSCP might be a more responsive outcome than gait speed to evaluate the efficacy of FPT in randomized trials.

    Gagliano-Jucá T, Li Z, Pencina KM, et al. The Stair Climb Power Test as an Efficacy Outcome in Randomized Trials of Function Promoting Therapies in Older Men. The Journals of Gerontology: Series A 2019. Stair Climb Power Test as an Efficacy Outcome in Randomized Trials of Function Promoting Therapies in Older Men