The Testosterone Trials

Seven coordinated trials of testosterone treatment in elderly men

Peter J. Snyder, Susan S. Ellenberg, Glenn R. Cunningham, Alvin M. Matsumoto, Shalender Bhasin, Elizabeth Barrett-Connor, Thomas M. Gill, John T. Farrar, David Cella, Raymond C. Rosen, Susan M. Resnick, Ronald S. Swerdloff, Jane A. Cauley, Denise Cifelli, Laura Fluharty, Marco Pahor, Kristine E. Ensrud, Cora E. Lewis, Mark E. Molitch, Jill P. Crandall & 16 others Christina Wang, Matthew J. Budoff, Nanette K. Wenger, Emile R. Mohler, Diane E. Bild, Nakela L. Cook, Tony M. Keaveny, David L. Kopperdahl, David Lee, Ann V. Schwartz, Thomas W. Storer, William B. Ershler, Cindy N. Roy, Leslie J. Raffel, Sergei Romashkan, Evan Hadley

Research output: Contribution to journalArticle

Abstract

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation.

Original languageEnglish (US)
Pages (from-to)362-375
Number of pages14
JournalClinical Trials
Volume11
Issue number3
DOIs
StatePublished - 2014

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Testosterone
Therapeutics
Aptitude
Bone Density
Cognition
Anemia
Testicular Diseases
Clinical Trials Data Monitoring Committees
Serum
Clinical Trials
Pituitary Diseases
Libido
Sample Size
Fatigue
Coronary Artery Disease
Coronary Vessels
Hemoglobins
Safety
Bone and Bones
Glucose

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

Snyder, P. J., Ellenberg, S. S., Cunningham, G. R., Matsumoto, A. M., Bhasin, S., Barrett-Connor, E., ... Hadley, E. (2014). The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men. Clinical Trials, 11(3), 362-375. https://doi.org/10.1177/1740774514524032

The Testosterone Trials : Seven coordinated trials of testosterone treatment in elderly men. / Snyder, Peter J.; Ellenberg, Susan S.; Cunningham, Glenn R.; Matsumoto, Alvin M.; Bhasin, Shalender; Barrett-Connor, Elizabeth; Gill, Thomas M.; Farrar, John T.; Cella, David; Rosen, Raymond C.; Resnick, Susan M.; Swerdloff, Ronald S.; Cauley, Jane A.; Cifelli, Denise; Fluharty, Laura; Pahor, Marco; Ensrud, Kristine E.; Lewis, Cora E.; Molitch, Mark E.; Crandall, Jill P.; Wang, Christina; Budoff, Matthew J.; Wenger, Nanette K.; Mohler, Emile R.; Bild, Diane E.; Cook, Nakela L.; Keaveny, Tony M.; Kopperdahl, David L.; Lee, David; Schwartz, Ann V.; Storer, Thomas W.; Ershler, William B.; Roy, Cindy N.; Raffel, Leslie J.; Romashkan, Sergei; Hadley, Evan.

In: Clinical Trials, Vol. 11, No. 3, 2014, p. 362-375.

Research output: Contribution to journalArticle

Snyder, PJ, Ellenberg, SS, Cunningham, GR, Matsumoto, AM, Bhasin, S, Barrett-Connor, E, Gill, TM, Farrar, JT, Cella, D, Rosen, RC, Resnick, SM, Swerdloff, RS, Cauley, JA, Cifelli, D, Fluharty, L, Pahor, M, Ensrud, KE, Lewis, CE, Molitch, ME, Crandall, JP, Wang, C, Budoff, MJ, Wenger, NK, Mohler, ER, Bild, DE, Cook, NL, Keaveny, TM, Kopperdahl, DL, Lee, D, Schwartz, AV, Storer, TW, Ershler, WB, Roy, CN, Raffel, LJ, Romashkan, S & Hadley, E 2014, 'The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men', Clinical Trials, vol. 11, no. 3, pp. 362-375. https://doi.org/10.1177/1740774514524032
Snyder PJ, Ellenberg SS, Cunningham GR, Matsumoto AM, Bhasin S, Barrett-Connor E et al. The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men. Clinical Trials. 2014;11(3):362-375. https://doi.org/10.1177/1740774514524032
Snyder, Peter J. ; Ellenberg, Susan S. ; Cunningham, Glenn R. ; Matsumoto, Alvin M. ; Bhasin, Shalender ; Barrett-Connor, Elizabeth ; Gill, Thomas M. ; Farrar, John T. ; Cella, David ; Rosen, Raymond C. ; Resnick, Susan M. ; Swerdloff, Ronald S. ; Cauley, Jane A. ; Cifelli, Denise ; Fluharty, Laura ; Pahor, Marco ; Ensrud, Kristine E. ; Lewis, Cora E. ; Molitch, Mark E. ; Crandall, Jill P. ; Wang, Christina ; Budoff, Matthew J. ; Wenger, Nanette K. ; Mohler, Emile R. ; Bild, Diane E. ; Cook, Nakela L. ; Keaveny, Tony M. ; Kopperdahl, David L. ; Lee, David ; Schwartz, Ann V. ; Storer, Thomas W. ; Ershler, William B. ; Roy, Cindy N. ; Raffel, Leslie J. ; Romashkan, Sergei ; Hadley, Evan. / The Testosterone Trials : Seven coordinated trials of testosterone treatment in elderly men. In: Clinical Trials. 2014 ; Vol. 11, No. 3. pp. 362-375.
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abstract = "Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation.",
author = "Snyder, {Peter J.} and Ellenberg, {Susan S.} and Cunningham, {Glenn R.} and Matsumoto, {Alvin M.} and Shalender Bhasin and Elizabeth Barrett-Connor and Gill, {Thomas M.} and Farrar, {John T.} and David Cella and Rosen, {Raymond C.} and Resnick, {Susan M.} and Swerdloff, {Ronald S.} and Cauley, {Jane A.} and Denise Cifelli and Laura Fluharty and Marco Pahor and Ensrud, {Kristine E.} and Lewis, {Cora E.} and Molitch, {Mark E.} and Crandall, {Jill P.} and Christina Wang and Budoff, {Matthew J.} and Wenger, {Nanette K.} and Mohler, {Emile R.} and Bild, {Diane E.} and Cook, {Nakela L.} and Keaveny, {Tony M.} and Kopperdahl, {David L.} and David Lee and Schwartz, {Ann V.} and Storer, {Thomas W.} and Ershler, {William B.} and Roy, {Cindy N.} and Raffel, {Leslie J.} and Sergei Romashkan and Evan Hadley",
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T1 - The Testosterone Trials

T2 - Seven coordinated trials of testosterone treatment in elderly men

AU - Snyder, Peter J.

AU - Ellenberg, Susan S.

AU - Cunningham, Glenn R.

AU - Matsumoto, Alvin M.

AU - Bhasin, Shalender

AU - Barrett-Connor, Elizabeth

AU - Gill, Thomas M.

AU - Farrar, John T.

AU - Cella, David

AU - Rosen, Raymond C.

AU - Resnick, Susan M.

AU - Swerdloff, Ronald S.

AU - Cauley, Jane A.

AU - Cifelli, Denise

AU - Fluharty, Laura

AU - Pahor, Marco

AU - Ensrud, Kristine E.

AU - Lewis, Cora E.

AU - Molitch, Mark E.

AU - Crandall, Jill P.

AU - Wang, Christina

AU - Budoff, Matthew J.

AU - Wenger, Nanette K.

AU - Mohler, Emile R.

AU - Bild, Diane E.

AU - Cook, Nakela L.

AU - Keaveny, Tony M.

AU - Kopperdahl, David L.

AU - Lee, David

AU - Schwartz, Ann V.

AU - Storer, Thomas W.

AU - Ershler, William B.

AU - Roy, Cindy N.

AU - Raffel, Leslie J.

AU - Romashkan, Sergei

AU - Hadley, Evan

PY - 2014

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N2 - Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation.

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