Testosterone Replacement Improves Aerobic Function in Mobility Limited Older Men with Low Testosterone

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: SUN 0071-0102-Male Reproduction: Hypogonadism and Reproductive Aging
Clinical
Sunday, June 22, 2014: 1:00 PM-3:00 PM
Hall F (McCormick Place West Building)

Poster Board SUN-0080
Thomas W Storer, Ph.D1, Joseph Mosholder, MS1, Ayan Elmi, MHA1, Renee Miciek, MS2, Thomas G Travison, PhD1, Shehzad Basaria, MD1 and Shalender Bhasin, MD1
1Brigham and Women's Hospital-Harvard Medical School, Boston, MA, 2Harvard School of Public Health, Boston, MA
BACKGROUND: Testosterone (T) replacement unequivocally increases skeletal muscle mass and strength but previous trials have not shown consistent improvements in physical function. We have shown that T stimulates mitochondrial biogenesis, increases red cell mass, 2,3 BPG, and tissue capillarity, all of which would be expected to increase tissue O2 delivery and aerobic performance. However, the effects of testosterone on aerobic performance in older men have not been evaluated.  To determine whether T supplementation improves measures of aerobic function [peak oxygen uptake (VO2peak) and the gas exchange lactate threshold (LTGE)], men aged ≥65yrs with mobility limitation (ML) and low total or free T levels were randomized to receive 10 mg of T (n=28) or placebo gel (n=36) daily for 6-mo (these participants comprise a subset of men participating in the Testosterone in Older Men with Mobility Limitation (TOM) Trial). We also determined the effects of T therapy on the age-related decline in VO2peak, which in the sedentary male population is expected to be approximately 0.4 mL/kg/min/year. METHODS: Subjects performed symptom limited cycle exercise using a 10-15 watt ramp protocol and breath-by-breath measures of oxygen uptake to determine VO2peak and LTGE.  VO2peak was selected from the last 15 sec of exercise and the V-slope method was used to detect LTGE. Changes in VO2peak within and between groups were compared using paired and unpaired t-tests, respectively. The change between groups for VO2peak vs. its expected change over treatment was examined with an unpaired t-test. RESULTS:  Baseline VO2peak and LTGE [mean (SD)] as well as their 6-mo changes [mean (SE)] are displayed in the table. VO2peak and LTGE improved slightly in the T arm while decreases were seen in the P group. The decrease in LTGE was significantly smaller for the T compared to P group. The 6-mo increase in VO2peak in the T arm represented 3.4 fold attenuation of the expected age-related decline, whereas men in the P group experienced accelerated decline at nearly twice the expected rate. CONCLUSION: Testosterone therapy in mobility-limited older men was associated with improved VO2peak and attenuated its age-related decline. Long-term intervention studies are needed to determine the durability of this effect and whether T affects fatigue.

                                          Testosterone                       Placebo                  Difference        

                                   Baseline       Change       Baseline       Change         in change         P

VO2peak(mL/kg/min) 20.5 (4.2)   0.68 (0.50)   19.2 (2.9)   -0.36 (0.43)     1.04 (0.66)     0.12

 LTGE(mL/kg/min)       13.7 (2.5)   0.0 (0.41)     14.0 (3.2)   -1.61 (0.49)    -1.49 (0.66)     0.03

Wilson TM, Tanaka H. Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status. Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H829-34.

Disclosure: SB: Investigator, Abbott Pharmaceuticals , Clinician, Eli Lilly & Company. SB: Principal Investigator, Abbott Laboratories, Principal Investigator, Eli Lilly & Company. Nothing to Disclose: TWS, JM, AE, RM, TGT

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: Funding: National Institutes on Aging (1UO1AG14369); Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679), and the Boston University Clinical and Translational Science Institute (1UL1RR025771).