The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men

被引：84

作者：

Snyder, Peter J. ^{[1
]}

Ellenberg, Susan S. ^{[2
]}

Cunningham, Glenn R. ^{[3
,4
]}

Matsumoto, Alvin M. ^{[5
]}

Bhasin, Shalender ^{[6
]}

Barrett-Connor, Elizabeth ^{[7
]}

Gill, Thomas M. ^{[8
]}

Farrar, John T. ^{[9
]}

Cella, David ^{[10
]}

Rosen, Raymond C. ^{[11
]}

Resnick, Susan M. ^{[12
]}

Swerdloff, Ronald S. ^{[13
]}

Cauley, Jane A. ^{[14
]}

Cifelli, Denise ^{[9
]}

Fluharty, Laura ^{[9
]}

Pahor, Marco ^{[15
]}

Ensrud, Kristine E. ^{[16
]}

Lewis, Cora E. ^{[17
]}

Molitch, Mark E. ^{[18
]}

Crandall, Jill P. ^{[19
]}

Wang, Christina ^{[13
]}

Budoff, Matthew J. ^{[20
]}

Wenger, Nanette K. ^{[21
]}

Mohler, Emile R., III ^{[22
,23
]}

Bild, Diane E. ^{[24
]}

Cook, Nakela L. ^{[25
]}

Keaveny, Tony M. ^{[26
,27
,28
]}

Kopperdahl, David L. ^{[28
]}

Lee, David ^{[28
]}

Schwartz, Ann V. ^{[29
]}

Storer, Thomas W. ^{[30
]}

Ershler, William B. ^{[31
]}

Roy, Cindy N. ^{[32
]}

Raffel, Leslie J. ^{[33
]}

Romashkan, Sergei ^{[34
]}

Hadley, Evan ^{[34
]}

机构：

[1] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[3] Baylor Coll Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA

[4] St Lukes Med Ctr, Houston, TX USA

[5] Univ Washington, Sch Med,Dept Vet Affairs Puget Sound Hlth Care Sy, Geriatr Res Educ & Clin Ctr,Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA

[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA USA

[7] Univ Calif San Diego, Sch Med, Dept Family & Preventat Med, La Jolla, CA 92093 USA

[8] Yale Univ, Sch Med, Div Geriatr Med, New Haven, CT USA

[9] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[10] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA

[11] New England Res Inst, Watertown, MA 02172 USA

[12] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[13] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Endocrinol, Torrance, CA USA

[14] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[15] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA

[16] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis VA Hlth Care Syst, Minneapolis, MN 55455 USA

[17] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA

[18] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[19] Albert Einstein Coll Med, Div Endocrinol & Geriatr, Bronx, NY 10467 USA

[20] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA

[21] Emory Univ, Sch Med, Div Cardiol, Emory Heart & Vasc Ctr, Atlanta, GA 30322 USA

[22] Univ Penn, Perelman Sch Med, Div Cardiovasc Dis, Philadelphia, PA 19104 USA

[23] Univ Penn, Perelman Sch Med, Sect Vasc Med, Philadelphia, PA 19104 USA

[24] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA

[25] NHLBI, Clin Applicat & Prevent Branch, Div Cardiovasc Sci, Ctr Cardiovasc Outcomes Res, Bethesda, MD 20892 USA

[26] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA

[27] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

[28] ON Diagnost, Berkeley, CA USA

[29] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[30] Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA USA

[31] Inst Adv Studies Aging, Div Hematol Oncol, Falls Church, VA USA

[32] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA

[33] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[34] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA

来源：

CLINICAL TRIALS | 2014年 / 11卷 / 03期

基金：

美国国家卫生研究院;

关键词：

LEAN BODY-MASS; BONE-MINERAL DENSITY; OLDER MEN; MUSCLE STRENGTH; TRANSDERMAL TESTOSTERONE; EXOGENOUS TESTOSTERONE; PHYSICAL PERFORMANCE; DOUBLE-BLIND; MEMORY IMPAIRMENT; SEXUAL FUNCTION;

D O I：

10.1177/1740774514524032

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

引用

页码：362 / 375

页数：14

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