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      The role of sex steroid hormones in the pathophysiology and treatment of sarcopenia

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          Abstract

          Sex steroids influence the maintenance and growth of muscles. Decline in androgens, estrogens and progesterone by aging leads to the loss of muscular function and mass, sarcopenia. These steroid hormones can interact with different signaling pathways through their receptors. To date, sex steroid hormone receptors and their exact roles are not completely defined in skeletal and smooth muscles. Although numerous studies focused on the effects of sex steroid hormones on different types of cells, still many unexplained molecular mechanisms in both skeletal and smooth muscle cells remain to be investigated. In this paper, many different molecular mechanisms that are activated or inhibited by sex steroids and those that influence the growth, proliferation, and differentiation of skeletal and smooth muscle cells are reviewed. Also, the similarities of cellular and molecular pathways of androgens, estrogens and progesterone in both skeletal and smooth muscle cells are highlighted. The reviewed signaling pathways and participating molecules can be targeted in the future development of novel therapeutics.

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          Epidemiology of sarcopenia among the elderly in New Mexico.

          R. Paul Ross, Markus Baumgartner, L. Romero … (1998)
          Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.
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            Growing roles for the mTOR pathway.

            Dos Sarbassov, Siraj M. Ali, David Sabatini (2005)
            The mammalian TOR (mTOR) pathway is a key regulator of cell growth and proliferation and increasing evidence suggests that its deregulation is associated with human diseases, including cancer and diabetes. The mTOR pathway integrates signals from nutrients, energy status and growth factors to regulate many processes, including autophagy, ribosome biogenesis and metabolism. Recent work identifying two structurally and functionally distinct mTOR-containing multiprotein complexes and TSC1/2, rheb, and AMPK as upstream regulators of mTOR is beginning to reveal how mTOR can sense diverse signals and produce a myriad of responses.
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              Adverse events associated with testosterone administration.

              Shehzad Basaria, Andrea D. Coviello, Thomas Travison … (2010)
              Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                Seung-Yup Ku
                Journal
                Journal ID (nlm-ta): Osteoporos Sarcopenia
                Journal ID (iso-abbrev): Osteoporos Sarcopenia
                Title: Osteoporosis and Sarcopenia
                Publisher: Korean Society of Osteoporosis
                ISSN (Print): 2405-5255
                ISSN (Electronic): 2405-5263
                Publication date PMC-release: 21 July 2016
                Publication date (Print): September 2016
                Publication date (Electronic): 21 July 2016
                Volume: 2
                Issue: 3
                Pages: 140-155
                Affiliations
                [a ]Department of Obstetrics and Gynecology, Korea University Guro Hospital, South Korea
                [b ]Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, South Korea
                [c ]Department of Obstetrics and Gynecology, Korea University Anam Hospital, Korea University College of Medicine, South Korea
                Author notes
                [∗ ]Corresponding author. Department of Obstetrics and Gynecology, Seoul National University, College of Medicine, 28 Yonkeun-dong Chongno-gu, Seoul 110-744, South Korea. jyhsyk@ 123456snu.ac.kr
                Article
                Publisher ID: S2405-5255(16)30032-2
                DOI: 10.1016/j.afos.2016.06.002
                PMC ID: 6372754
                PubMed ID: 30775480
                SO-VID: 3440b776-74f1-4ac1-9817-d68094d853a5
                Copyright © © 2016 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 18 April 2016
                Date revision received : 9 June 2016
                Date accepted : 17 June 2016
                Categories
                Subject: Review Article

                Keywords: sarcopenia,androgen,estrogen,progesterone,skeletal muscle,smooth muscle
                Data availability:
                Keywords: sarcopenia, androgen, estrogen, progesterone, skeletal muscle, smooth muscle

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