Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging
Testosterone use as anabolic therapy is controversial. Here, meta-analyses show that testosterone increases skeletal muscle mass and strength in androgen-deficient young men, older men and men with chronic illness; these data provide a compelling rationale for the development of selective androgen r...
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Veröffentlicht in: | Nature clinical practice. Endocrinology & metabolism 2006-03, Vol.2 (3), p.146-159 |
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creator | Bhasin, Shalender Calof, Olga M Storer, Thomas W Lee, Martin L Mazer, Norman A Jasuja, Ravi Montori, Victor M Gao, Wenqing Dalton, James T |
description | Testosterone use as anabolic therapy is controversial. Here, meta-analyses show that testosterone increases skeletal muscle mass and strength in androgen-deficient young men, older men and men with chronic illness; these data provide a compelling rationale for the development of selective androgen receptor modulators that mimic testosterone's effects without its side effects.
Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.
Key Points
Meta-analyses of clinical trials provide unequivocal evidence that testosterone administration increases skeletal muscle mass, muscle strength, and leg power; these anabolic effects of testosterone are dose-related
The effects of testosterone supplementation on physical function and clinical outcomes in older men with physical dysfunction and in men with chronic illness are unknown
Testosterone induces skeletal muscle fiber hypertrophy and increases the number of satellite cells
Testosterone increases muscle mass and decreases fat mass by promoting the diff |
doi_str_mv | 10.1038/ncpendmet0120 |
format | Article |
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Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.
Key Points
Meta-analyses of clinical trials provide unequivocal evidence that testosterone administration increases skeletal muscle mass, muscle strength, and leg power; these anabolic effects of testosterone are dose-related
The effects of testosterone supplementation on physical function and clinical outcomes in older men with physical dysfunction and in men with chronic illness are unknown
Testosterone induces skeletal muscle fiber hypertrophy and increases the number of satellite cells
Testosterone increases muscle mass and decreases fat mass by promoting the differentiation of mesenchymal multipotent cells into myogenic lineage and inhibiting their differentiation into the adipogenic lineage
An increase in hematocrit and increased risk of detection of prostate events are the most frequent adverse effects of testosterone administration in older men; the anabolic applications of testosterone are constrained by dose-limiting adverse events and concerns about long-term effects on the prostate and cardiovascular risk
Nonsteroidal selective androgen-receptor modulators that are free of adverse effects of testosterone and are preferentially anabolic hold great promise as anabolic therapies</description><identifier>ISSN: 1745-8366</identifier><identifier>ISSN: 1759-5029</identifier><identifier>EISSN: 1745-8374</identifier><identifier>EISSN: 1759-5037</identifier><identifier>DOI: 10.1038/ncpendmet0120</identifier><identifier>PMID: 16932274</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Aging ; Aging - drug effects ; Androgens ; Antiandrogens ; Body composition ; Care and treatment ; Chronic Disease - drug therapy ; Chronic diseases ; Chronic illnesses ; Chronic obstructive pulmonary disease ; Dosage and administration ; Drug Design ; Drug dosages ; Endocrinology ; Health aspects ; Health care ; HIV ; Hormone Replacement Therapy ; Human immunodeficiency virus ; Humans ; Medicine ; Medicine & Public Health ; Meta-analysis ; Middle age ; Muscle strength ; Muscle, Skeletal - drug effects ; Musculoskeletal system ; Organ Specificity ; Prostate ; Receptors, Androgen - drug effects ; review-article ; Testosterone ; Testosterone - adverse effects ; Testosterone - pharmacology ; Testosterone - therapeutic use</subject><ispartof>Nature clinical practice. Endocrinology & metabolism, 2006-03, Vol.2 (3), p.146-159</ispartof><rights>Springer Nature Limited 2006</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c547t-5eb7715098bd4b111f2c3b0531f9f3f5f22abbbaf411a38f352859f567a1402c3</citedby><cites>FETCH-LOGICAL-c547t-5eb7715098bd4b111f2c3b0531f9f3f5f22abbbaf411a38f352859f567a1402c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16932274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhasin, Shalender</creatorcontrib><creatorcontrib>Calof, Olga M</creatorcontrib><creatorcontrib>Storer, Thomas W</creatorcontrib><creatorcontrib>Lee, Martin L</creatorcontrib><creatorcontrib>Mazer, Norman A</creatorcontrib><creatorcontrib>Jasuja, Ravi</creatorcontrib><creatorcontrib>Montori, Victor M</creatorcontrib><creatorcontrib>Gao, Wenqing</creatorcontrib><creatorcontrib>Dalton, James T</creatorcontrib><title>Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging</title><title>Nature clinical practice. Endocrinology & metabolism</title><addtitle>Nat Rev Endocrinol</addtitle><addtitle>Nat Clin Pract Endocrinol Metab</addtitle><description>Testosterone use as anabolic therapy is controversial. Here, meta-analyses show that testosterone increases skeletal muscle mass and strength in androgen-deficient young men, older men and men with chronic illness; these data provide a compelling rationale for the development of selective androgen receptor modulators that mimic testosterone's effects without its side effects.
Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.
Key Points
Meta-analyses of clinical trials provide unequivocal evidence that testosterone administration increases skeletal muscle mass, muscle strength, and leg power; these anabolic effects of testosterone are dose-related
The effects of testosterone supplementation on physical function and clinical outcomes in older men with physical dysfunction and in men with chronic illness are unknown
Testosterone induces skeletal muscle fiber hypertrophy and increases the number of satellite cells
Testosterone increases muscle mass and decreases fat mass by promoting the differentiation of mesenchymal multipotent cells into myogenic lineage and inhibiting their differentiation into the adipogenic lineage
An increase in hematocrit and increased risk of detection of prostate events are the most frequent adverse effects of testosterone administration in older men; the anabolic applications of testosterone are constrained by dose-limiting adverse events and concerns about long-term effects on the prostate and cardiovascular risk
Nonsteroidal selective androgen-receptor modulators that are free of adverse effects of testosterone and are preferentially anabolic hold great promise as anabolic therapies</description><subject>Aging</subject><subject>Aging - drug effects</subject><subject>Androgens</subject><subject>Antiandrogens</subject><subject>Body composition</subject><subject>Care and treatment</subject><subject>Chronic Disease - drug therapy</subject><subject>Chronic diseases</subject><subject>Chronic illnesses</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Dosage and administration</subject><subject>Drug Design</subject><subject>Drug dosages</subject><subject>Endocrinology</subject><subject>Health aspects</subject><subject>Health care</subject><subject>HIV</subject><subject>Hormone Replacement Therapy</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meta-analysis</subject><subject>Middle age</subject><subject>Muscle strength</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Musculoskeletal system</subject><subject>Organ Specificity</subject><subject>Prostate</subject><subject>Receptors, Androgen - drug effects</subject><subject>review-article</subject><subject>Testosterone</subject><subject>Testosterone - adverse effects</subject><subject>Testosterone - pharmacology</subject><subject>Testosterone - therapeutic use</subject><issn>1745-8366</issn><issn>1759-5029</issn><issn>1745-8374</issn><issn>1759-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ks9rHSEQx5fS0qRpj70WoedN_LE-3R4KIf0VCPTSnkXdcZ9hV7fqBvLf1yaP9_IgRcFx5jsfZnSa5j3B5wQzeRHsAmGYoWBC8YvmlIiOt5KJ7uXe3mxOmjc532LcSUrI6-aEbHpGqehOm_svaR3Rdch-3JZPqEAuMRdIMQDSYUAZJrDF3z3cUhwhoAQWlhITmuOwTrpaGem6gzZx8haVLSS9eMjIVZHdVlb1-mkKkPMDVI8-jG-bV05PGd7tzrPm97evv65-tDc_v19fXd60lneitByMEITjXpqhM4QQRy0zmDPiesccd5RqY4x2HSGaScc4lbx3fCM06XDVnjWfH7nLamYYLISS9KSW5Ged7lXUXh1Hgt-qMd4pigWVQlbAxx0gxT9rfSB1G9cUas2KCCm46DGlB9WoJ1A-uFhhdvbZqksipWACi76qzp9R1TXA7G19dOer_yihfUywKeacwO0LJ1j9GwB1NABV_-Fptwf17scPFeQaCiOkJ938h7hrLOiyJtgTj1V_ASdfzK8</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Bhasin, Shalender</creator><creator>Calof, Olga M</creator><creator>Storer, Thomas W</creator><creator>Lee, Martin L</creator><creator>Mazer, Norman A</creator><creator>Jasuja, Ravi</creator><creator>Montori, Victor M</creator><creator>Gao, Wenqing</creator><creator>Dalton, James T</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20060301</creationdate><title>Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging</title><author>Bhasin, Shalender ; Calof, Olga M ; Storer, Thomas W ; Lee, Martin L ; Mazer, Norman A ; Jasuja, Ravi ; Montori, Victor M ; Gao, Wenqing ; Dalton, James T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c547t-5eb7715098bd4b111f2c3b0531f9f3f5f22abbbaf411a38f352859f567a1402c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Aging</topic><topic>Aging - drug effects</topic><topic>Androgens</topic><topic>Antiandrogens</topic><topic>Body composition</topic><topic>Care and treatment</topic><topic>Chronic Disease - drug therapy</topic><topic>Chronic diseases</topic><topic>Chronic illnesses</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Dosage and administration</topic><topic>Drug Design</topic><topic>Drug dosages</topic><topic>Endocrinology</topic><topic>Health aspects</topic><topic>Health care</topic><topic>HIV</topic><topic>Hormone Replacement Therapy</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meta-analysis</topic><topic>Middle age</topic><topic>Muscle strength</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Musculoskeletal system</topic><topic>Organ Specificity</topic><topic>Prostate</topic><topic>Receptors, Androgen - drug effects</topic><topic>review-article</topic><topic>Testosterone</topic><topic>Testosterone - adverse effects</topic><topic>Testosterone - pharmacology</topic><topic>Testosterone - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhasin, Shalender</creatorcontrib><creatorcontrib>Calof, Olga M</creatorcontrib><creatorcontrib>Storer, Thomas W</creatorcontrib><creatorcontrib>Lee, Martin L</creatorcontrib><creatorcontrib>Mazer, Norman A</creatorcontrib><creatorcontrib>Jasuja, Ravi</creatorcontrib><creatorcontrib>Montori, Victor M</creatorcontrib><creatorcontrib>Gao, Wenqing</creatorcontrib><creatorcontrib>Dalton, James T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature clinical practice. Endocrinology & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhasin, Shalender</au><au>Calof, Olga M</au><au>Storer, Thomas W</au><au>Lee, Martin L</au><au>Mazer, Norman A</au><au>Jasuja, Ravi</au><au>Montori, Victor M</au><au>Gao, Wenqing</au><au>Dalton, James T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging</atitle><jtitle>Nature clinical practice. Endocrinology & metabolism</jtitle><stitle>Nat Rev Endocrinol</stitle><addtitle>Nat Clin Pract Endocrinol Metab</addtitle><date>2006-03-01</date><risdate>2006</risdate><volume>2</volume><issue>3</issue><spage>146</spage><epage>159</epage><pages>146-159</pages><issn>1745-8366</issn><issn>1759-5029</issn><eissn>1745-8374</eissn><eissn>1759-5037</eissn><abstract>Testosterone use as anabolic therapy is controversial. Here, meta-analyses show that testosterone increases skeletal muscle mass and strength in androgen-deficient young men, older men and men with chronic illness; these data provide a compelling rationale for the development of selective androgen receptor modulators that mimic testosterone's effects without its side effects.
Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with β-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.
Key Points
Meta-analyses of clinical trials provide unequivocal evidence that testosterone administration increases skeletal muscle mass, muscle strength, and leg power; these anabolic effects of testosterone are dose-related
The effects of testosterone supplementation on physical function and clinical outcomes in older men with physical dysfunction and in men with chronic illness are unknown
Testosterone induces skeletal muscle fiber hypertrophy and increases the number of satellite cells
Testosterone increases muscle mass and decreases fat mass by promoting the differentiation of mesenchymal multipotent cells into myogenic lineage and inhibiting their differentiation into the adipogenic lineage
An increase in hematocrit and increased risk of detection of prostate events are the most frequent adverse effects of testosterone administration in older men; the anabolic applications of testosterone are constrained by dose-limiting adverse events and concerns about long-term effects on the prostate and cardiovascular risk
Nonsteroidal selective androgen-receptor modulators that are free of adverse effects of testosterone and are preferentially anabolic hold great promise as anabolic therapies</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16932274</pmid><doi>10.1038/ncpendmet0120</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aging Aging - drug effects Androgens Antiandrogens Body composition Care and treatment Chronic Disease - drug therapy Chronic diseases Chronic illnesses Chronic obstructive pulmonary disease Dosage and administration Drug Design Drug dosages Endocrinology Health aspects Health care HIV Hormone Replacement Therapy Human immunodeficiency virus Humans Medicine Medicine & Public Health Meta-analysis Middle age Muscle strength Muscle, Skeletal - drug effects Musculoskeletal system Organ Specificity Prostate Receptors, Androgen - drug effects review-article Testosterone Testosterone - adverse effects Testosterone - pharmacology Testosterone - therapeutic use |
title | Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging |
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