Testosterone Threshold Levels and Lean Tissue Mass Targets Needed to Enhance Skeletal Muscle Strength and Function: The HORMA Trial

Sattler, Fred R.; Bhasin, Shalender; He, Jun; Chou, Chih-Ping; Castaneda‐Sceppa, Carmen; Yarasheski, Kevin E.; Binder, Ellen F.; Schroeder, E. Todd; Kawakubo, Miwa; Zhang, Anqi; Roubenoff, Ronenn; Azen, Stanley P.

doi:10.1093/gerona/glq183

Cited by 48 publications

(39 citation statements)

References 28 publications

(15 reference statements)

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“…35 In a third study, 112 (65–90 year-old) community-dwelling men were randomized to placebo, 3 or 5 μg/kg/day of rhGH or transdermal testosterone gel (5-or-10 g/d) for 16 weeks. 36,37 Total and appendicular LBM were enhanced by addition of rhGH. For men who achieved at least 1.5 kg increases in total and 0.8 kg increases in appendicular LBM, there were significant increases of ≥30% in 1-RM strength.…”

Section: Treatment To Enhance Gh/igf-1 Status and Improve Performancementioning

confidence: 93%

Growth hormone in the aging male

Sattler

2013

Best Practice & Research Clinical Endocrinology & Metab

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Secretion of growth hormone (GH) and IGF-1 levels decline during advancing years-of-life. These changes (somatopause) are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function. For GH treatment to be considered for anti-aging, improved longevity, organ-specific function, or quality of life should be demonstrable. A limited number of controlled studies suggest that GH supplementation in older men increases lean mass by ~2 kg with similar reductions in fat mass. There is little evidence that GH treatment improves muscle strength and performance (e.g. walking speed or ability to climb stairs) or quality of life. The GHRH agonist (tesamorelin) restores normal GH pulsatility and amplitude, selectively reduces visceral fat, intima media thickness and triglycerides, and improves cognitive function in older persons. This report critically reviews the potential for GH augmentation during aging with emphasis on men since women appear more resistant to treatment.

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Section: Treatment To Enhance Gh/igf-1 Status and Improve Performancementioning

confidence: 93%

Growth hormone in the aging male

Sattler

2013

Best Practice & Research Clinical Endocrinology & Metab

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“…Fasting glucose, insulin and adiponectin levels in plasma were assayed using an automated chemiluminescent analyzer (Immulite 1000, Siemens Healthcare Diagnostics, Deerfield, IL) 33 . Plasma for lipopolysaccharide (LPS) was quantified using the Endpoint Chromogenic LAL assay (Lonza, Basel, Switzerland) 34 .…”

Section: Methodsmentioning

confidence: 99%

Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation

Sattler

Letendre³

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Design Cross-sectional Setting Six Academic Centers Participants 152 patients with plasma HIV RNA <1,000copies/ml had clinical evaluations and cognitive function quantified by global deficit scores (GDS). Outcome Measures GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. Results WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year of the index visit, GDS remained worse in patients with IL-6 levels in the high-versus-low tertile (p=0.02). Path analysis to explore potential mediators of NCI produced a strong, integrated model for patients in the high CSF sCD40L tertile. In this model, WC affected GDS both directly and via a second path that was mediated by IL-6. Inclusion of plasma sCD14 levels strengthened the model. NCI was more common in men and for individuals with components of the metabolic syndrome. Conclusions NC function was significantly linked to abdominal obesity, systemic inflammation (high IL-6), and immune activation in plasma (high sCD14) and CSF (high sCD40L). Abdominal obesity, inflammation, and CNS immune activation are potential therapeutic targets for NCI in HIV+ patients.

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“…In our previous intent to treat report, there was sizable heterogeneity in outcomes within the treatment assignment groups. Although changes in serum testosterone and IGF-1 levels were also heterogeneous in the treatment groups, they were directly related to changes in LBM, which were necessary to enhance muscle performance (Sattler et al 2011). Therefore, in this secondary analysis we sought to determine if the effects of testosterone alone and testosterone plus rhGH on lean mass and strength at 8 and 16 weeks were corroborated by changes in muscle performance.…”

Section: Methodsmentioning

confidence: 99%

Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation

Schroeder

Yarasheski

et al. 2011

Eur J Appl Physiol

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We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwelling men. Participants received transdermal T at either 5 or 10 g/day as well as rhGH at 0, 3.0 or 5.0 µg/kg/day for 16 weeks. Body composition was determined by dual-energy X-ray absorptiometry (DEXA) and muscle performance by composite one-repetition maximum (1-RM) strength and strength per unit of lean mass (muscle quality, MQ) for five major muscle groups (upper and lower body) at baseline, week 8 and 17. The average change in total LM at study week 8 compared with baseline was 1.50 ± 1.54 kg (P < 0.0001) in the T only group and 2.64 ± 1.7 (P < 0.0001) in the T + rhGH group and at week 17 was 1.46 ± 1.48 kg (P < 0.0001) in the T only group and 2.14 ± 1.96 kg (P < 0.0001) in the T + rhGH group. 1-RM strength improved modestly in both groups combined (12.0 ± 23.9%, P < 0.0001) at week 8 but at week 17 these changes were twofold greater (24.7 ± 31.0%, P < 0.0001). MQ did not significantly change from baseline to week 8 but increased for the entire cohort, T only, and T + rhGH groups by week 17 (P < 0.001). Despite sizeable increases in LM measurements at week 8, tests of muscle performance did not show substantive improvements at this time point.

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Testosterone Threshold Levels and Lean Tissue Mass Targets Needed to Enhance Skeletal Muscle Strength and Function: The HORMA Trial

Cited by 48 publications

References 28 publications

Growth hormone in the aging male

Growth hormone in the aging male

Abdominal Obesity Contributes to Neurocognitive Impairment in HIV-Infected Patients With Increased Inflammation and Immune Activation

Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation

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