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Cited by 363Hormonal and reproductive studiesBone health and osteoporosis researchMenopause: Health Impacts and Treatments

Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial

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Snyder, Peter J., Kopperdahl, David L., Stephens-Shields, Alisa J., Ellenberg, Susan S., Cauley, Jane A., Ensrud, Kristine E., Lewis, Cora E., Barrett-Connor, Elizabeth +16 more·2017·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2016.9539PMC PMC5433755
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Abstract

Importance: As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture. Objective: To determine whether testosterone treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength. Design, Setting, and Participants: Placebo-controlled, double-blind trial with treatment allocation by minimization at 9 US academic medical centers of men 65 years or older with 2 testosterone concentrations averaging less than 275 ng/L participating in the Testosterone Trials from December 2011 to June 2014. The analysis was a modified intent-to-treat comparison of treatment groups by multivariable linear regression adjusted for balancing factors as required by minimization. Interventions: Testosterone gel, adjusted to maintain the testosterone level within the normal range for young men, or placebo gel for 1 year. Main Outcomes and Measures: Spine and hip vBMD was determined by quantitative computed tomography at baseline and 12 months. Bone strength was estimated by finite element analysis of quantitative computed tomography data. Areal BMD was assessed by dual energy x-ray absorptiometry at baseline and 12 months. Results: There were 211 participants (mean [SD] age, 72.3 [5.9] years; 86% white; mean [SD] body mass index, 31.2 [3.4]). Testosterone treatment was associated with significantly greater increases than placebo in mean spine trabecular vBMD (7.5%; 95% CI, 4.8% to 10.3% vs 0.8%; 95% CI, -1.9% to 3.4%; treatment effect, 6.8%; 95% CI, 4.8%-8.7%; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD, and mean estimated strength of spine trabecular bone (10.8%; 95% CI, 7.4% to 14.3% vs 2.4%; 95% CI, -1.0% to 5.7%; treatment effect, 8.5%; 95% CI, 6.0%-10.9%; P < .001), spine peripheral bone, and hip trabecular and peripheral bone. The estimated strength increases were greater in trabecular than peripheral bone and greater in the spine than hip. Testosterone treatment increased spine areal BMD but less than vBMD. Conclusions and Relevance: Testosterone treatment for 1 year of older men with low testosterone significantly increased vBMD and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. A larger, longer trial could determine whether this treatment also reduces fracture risk. Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

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  • Testosterone administration in elderly men improves sexual function, lean body mass, physical function, strength, protein synthesis, cholesterol, and bone density.

    “These trials and other independent studies found that T administration in elderly men resulted in improvements in sexual function,202, 203 lean body mass,204, 205 physical function,206 strength,25, 205, 207 protein synthesis,25 cholesterol,204, 205, 208 and bone density.209”

    From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [209]

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Authors
Snyder, P. J., Kopperdahl, D. L., Stephens-Shields, A. J., Ellenberg, S. S., Cauley, J. A., Ensrud, K. E., Lewis, C. E., Barrett-Connor, E., Schwartz, A. V., Lee, D. C., Bhasin, S., Cunningham, G. R., Gill, T. M., Matsumoto, A. M., Swerdloff, R. S., Basaria, S., Diem, S. J., Wang, C., Hou, X., Cifelli, D., Dougar, D., Zeldow, B., Bauer, D. C., & Keaveny, T. M.
Affiliations
  • University of Pennsylvania (US)
  • O.N. Diagnostics (United States) (US)
  • Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • University of Pittsburgh (US)
  • University of Minnesota (US)
  • University of Alabama at Birmingham (US)
  • University of California San Diego (US)
  • University of California, San Francisco (US)
  • Brigham and Women's Hospital (US)
  • Baylor College of Medicine (US)
  • Yale University (US)
  • University of Washington (US)
  • University of California, Los Angeles (US)
  • University of California, Berkeley (US)
Corresponding author
Snyder, Peter J.
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2017-04-01
Volume
177
Issue
4
Pages
471
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2016.9539
PMC
PMC5433755
OpenAlex
W2591696989
Cited by
363
References
47
Citations by year
2026: 37 · 2025: 47 · 2024: 37 · 2023: 37 · 2022: 41 · 2021: 44 · 2020: 30 · 2019: 34 · 2018: 32 · 2017: 22 · 2016: 1
FWCI
25.39
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (5p60dk079626-05, UL1TR000142, 5p30ag031679-15, UL1TR001863)
  • National Institute on Aging (U01AG030644, R01AG037679, K07AG043587, P30-AG031679, P30AG021342)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-079626, P30DK079626)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
testosterone replacement therapy, androgen deficiency, hypogonadism, older men, volumetric bone mineral density, bone strength, trabecular bone, hip bone, spine bone, testosterone gel, finite element analysis, fracture risk, bone mineral density, hormone replacement therapy, osteoporosis prevention
MeSH terms
Aged, Androgens, Double-Blind Method, Drug Administration Routes, Hip Fractures, Humans, Lumbar Vertebrae, Male, Testosterone, Tomography, X-Ray Computed, Absorptiometry, Photon, Bone Density, Spinal Fractures, Treatment Outcome, Drug Monitoring

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