Grace Huang1, Karol M Pencina1, Zhuoying Li1, Shehzad Basaria1, Shalender Bhasin1, Thomas G Travison2, Thomas W Storer1, S Mitchell Harman3,4, Panayiotis Tsitouras3,5. 1. Section of Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Brigham and Women's Hospital-Harvard Medical School, Boston, Massachusetts. 2. Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. 3. Kronos Longevity Research Institute, Phoenix, Arizona. 4. Phoenix VA Health Care System, Phoenix, Arizona. 5. Department of Geriatric Medicine, University of Oklahoma HSC, Oklahoma City, Oklahoma.
Abstract
Background: Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. Methods: The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent anoctreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. Results: There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Conclusion:Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.
RCT Entities:
Background: Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. Methods: The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. Results: There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Conclusion:Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.
Authors: Thomas G Travison; Shehzad Basaria; Thomas W Storer; Alan M Jette; Renee Miciek; Wildon R Farwell; Karen Choong; Kishore Lakshman; Norman A Mazer; Andrea D Coviello; Philip E Knapp; Jagadish Ulloor; Anqi Zhang; Brad Brooks; Ahn-Hoa Nguyen; Richard Eder; Nathan LeBrasseur; Ayan Elmi; Erica Appleman; Leife Hede-Brierley; Geeta Bhasin; Ashmeet Bhatia; Antonio Lazzari; Samuel Davis; Pengsheng Ni; Lauren Collins; Shalender Bhasin Journal: J Gerontol A Biol Sci Med Sci Date: 2011-06-22 Impact factor: 6.053
Authors: Emily J Gianatti; Philippe Dupuis; Rudolf Hoermann; Boyd J Strauss; John M Wentworth; Jeffrey D Zajac; Mathis Grossmann Journal: Diabetes Care Date: 2014-05-07 Impact factor: 19.112
Authors: Joshua W Knowles; Themistocles L Assimes; Philip S Tsao; Andrea Natali; Andrea Mari; Thomas Quertermous; Gerald M Reaven; Fahim Abbasi Journal: Metabolism Date: 2012-11-12 Impact factor: 8.694
Authors: Stine A Holmboe; Tina K Jensen; Allan Linneberg; Thomas Scheike; Betina H Thuesen; Niels E Skakkebaek; Anders Juul; Anna-Maria Andersson Journal: J Clin Endocrinol Metab Date: 2016-06-10 Impact factor: 5.958
Authors: T Hugh Jones; Stefan Arver; Hermann M Behre; Jacques Buvat; Eric Meuleman; Ignacio Moncada; Antonio Martin Morales; Maurizio Volterrani; Ann Yellowlees; Julian D Howell; Kevin S Channer Journal: Diabetes Care Date: 2011-03-08 Impact factor: 19.112
Authors: Jin Choul Chai; Guo-Chong Chen; Bing Yu; Jiaqian Xing; Jun Li; Tasneem Khambaty; Krista M Perreira; Marisa J Perera; Denise C Vidot; Sheila F Castaneda; Elizabeth Selvin; Casey M Rebholz; Martha L Daviglus; Jianwen Cai; Linda Van Horn; Carmen R Isasi; Qi Sun; Meredith Hawkins; Xiaonan Xue; Eric Boerwinkle; Robert C Kaplan; Qibin Qi Journal: Diabetes Date: 2022-06-01 Impact factor: 9.337
Authors: Biagio Barone; Luigi Napolitano; Marco Abate; Luigi Cirillo; Pasquale Reccia; Francesco Passaro; Carmine Turco; Simone Morra; Francesco Mastrangelo; Antonio Scarpato; Ugo Amicuzi; Vincenzo Morgera; Lorenzo Romano; Francesco Paolo Calace; Savio Domenico Pandolfo; Luigi De Luca; Achille Aveta; Enrico Sicignano; Massimiliano Trivellato; Gianluca Spena; Carlo D'Alterio; Giovanni Maria Fusco; Raffaele Vitale; Davide Arcaniolo; Felice Crocetto Journal: Int J Mol Sci Date: 2022-03-24 Impact factor: 5.923
Authors: João Martin Martins; Mafalda de Pina Jorge; Catarina Martins Maia; João Roque; Carlos Lemos; Daniel Nunes; Dinis Reis; Catarina Mota Journal: Int J Endocrinol Date: 2021-06-04 Impact factor: 3.257
Authors: Michael W O'Reilly; Marija Glisic; Balachandran Kumarendran; Anuradhaa Subramanian; Konstantinos N Manolopoulos; Abd A Tahrani; Deepi Keerthy; Taulant Muka; Konstantinos A Toulis; Wasim Hanif; G Neil Thomas; Oscar H Franco; Wiebke Arlt; Krishnarajah Nirantharakumar Journal: Clin Endocrinol (Oxf) Date: 2018-10-23 Impact factor: 3.478