Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial.
OBJECTIVE
Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown.


OBJECTIVE
To determine the effect of testosterone administration on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels.


METHODS
Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012.


METHODS
One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL.


METHODS
Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health-related quality of life.


RESULTS
Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, -0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, -10.8 Agatston units/year; 95% CI, -45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group.


CONCLUSIONS
Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men.


BACKGROUND
clinicaltrials.gov Identifier: NCT00287586.
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Shehzad
S
Basaria
Kronos Longevity Research Institute, Phoenix, Arizona3Phoenix VA Health Care System, Phoenix, Arizona.
S Mitchell
SM
Harman
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts11Institute for Aging Research, Hebrew SeniorLife, Boston, Mass.
Thomas G
TG
Travison
Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles.
Howard
H
Hodis
Kronos Longevity Research Institute, Phoenix, Arizona5DWR Department of Geriatric Medicine, University of Oklahoma, Oklahoma City.
Panayiotis
P
Tsitouras
Los Angeles Biomedical Research Institute, Division of Cardiology, Harbor-UCLA Medical Center, Torrance, California.
Matthew
M
Budoff
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Karol M
KM
Pencina
Division of Cardiology, Boston University School of Medicine, Boston, Massachusetts.
Joseph
J
Vita
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California.
Connie
C
Dzekov
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland10Division of Endocrinology, Boston University School of Medicine, Boston, Massachusetts.
Norman A
NA
Mazer
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Andrea D
AD
Coviello
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Philip E
PE
Knapp
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Kathleen
K
Hally
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Emma
E
Pinjic
Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles.
Mingzhu
M
Yan
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Thomas W
TW
Storer
Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Shalender
S
Bhasin
D000368:Aged; D050197:Atherosclerosis / Q000139:chemically induced*; D002118:Calcium / Q000032:analysis; D059168:Carotid Intima-Media Thickness; D003331:Coronary Vessels / Q000737:chemistry; D018450:Disease Progression; D004311:Double-Blind Method; D006304:Health Status; D006801:Humans; D006973:Hypertension; D008297:Male; D008875:Middle Aged; D009765:Obesity; D011788:Quality of Life; D012735:Sexual Dysfunction, Physiological / Q000150:complications / Q000209:etiology; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use; D016896:Treatment Outcome
D013739:Testosterone; D002118:Calcium