Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study

Abstract

Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged ≥65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men. © 2017 American Society for Bone and Mineral Research.

Keywords: FALLS; GENERAL POPULATION STUDIES; MEN; PHYSICAL PERFORMANCE; SEX STEROIDS.

Figure 1

Smoothed plots of the likelihood of incident falls according to serum total T and BioT concentrations. Odds ratios (ORs, solid line) and 95% confidence intervals (CIs, dashed lines) were estimated by restricted cubic spline analyses using the median total testosterone (T, 447 ng/dL) (Fig. 1 A) or bioavailable testosterone (BioT, 236 ng/dL) (Fig. 1 B) concentration as reference values. Three knots positioned at the 25th, 50th, and 75th percentiles of the serum total T or BioT concentration were used. The models were adjusted for age at baseline, prevalent falls, race, morning sampling (yes/no), report number, site, and MrOS study cohort. The cut‐offs for the 25th and 75th percentiles are 346 and 569 ng/dL, respectively, for total T, and 190 and 292 ng/dL, respectively, for BioT.