Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: a factorial design RCT

Authors: BISCHOFF-FERRARI, HEIKE - University Of Zurich; KISTTLER-FISCHBACHER, MELANIE - University Of Zurich; GAENGLER, STEPHANIE - University Of Zurich; MUNZER, THOMAS - Geriatrische Klinik St Gallen; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LANG, WEI - University Of Zurich; THEILER, ROBERT - University Of Zurich; EGLI, ANDREAS - University Of Zurich; ORAV, JOHN - Harvard School Of Public Health; FREYSTETTER, GREGOR - University Of Zurich

Submitted to: Journal of Nutrition Health and Aging
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2024
Publication Date: 5/1/2024
Citation: Bischoff-Ferrari, H.A., Kisttler-Fischbacher, M., Gaengler, S., Munzer, T., Dawson-Hughes, B., Lang, W., Theiler, R., Egli, A., Orav, J.E., Freystetter, G. 2024. Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: A factorial design RCT. Journal of Nutrition Health and Aging. https://doi.org/10.1016/j.jnha.2024.100217.
DOI: https://doi.org/10.1016/j.jnha.2024.100217

Interpretive Summary: Low testosterone blood levels have been associated with an increased risk of falling in older men, however evidence from randomized controlled trials on fall prevention is limited. Also, combined effects with vitamin D supplementation are unknown. This randomized, placebo-controlled clinical trial was conducted to determine whether daily treatment with testosterone and/or monthly treatment with vitamin D in replacement amounts would lower risk of falling over a 1-year period in older pre-frail men. Over 12 months, 37 participants had 72 falls. The odds of falling were not significantly reduced by testosterone versus no testosterone or by vitamin D versus no vitamin D. Testosterone did increase lean mass in the arms and legs compared to the no testosterone group, and it improved walking speed compared to placebo. No other benefits of testosterone or vitamin D were documented for lower extremity function. We conclude that testosterone treatment is not effective in reducing risk of falling in older men with low testosterone levels and vitamin D supplementation does not lower risk of falling in this largely vitamin D replete population.

Technical Abstract: Objective: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men age 65 and older. Design: 2 x 2 factorial design randomized controlled trial, follow up of 12 months. Methods: Hypogonadism was defined as total testosterone <11.3 nmol/l and pre-frailty as =1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement. Results: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were prescreened). Mean age was 72.2 years, serum total testosterone was 10.8 +/-3.0 nmol/L, and 20.9% had 25(OH)D levels below 20 ng/ml. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo. Conclusion: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.