Testosterone, dihydrotestosterone, bone density, and hip fracture risk among older men: The Cardiovascular Health Study

Metabolism. 2021 Jan:114:154399. doi: 10.1016/j.metabol.2020.154399. Epub 2020 Oct 12.

Abstract

Background: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM).

Methods: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439).

Results: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models.

Conclusions: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.

Keywords: Androgen; Bone mineral density; Dihydrotestosterone; Hip fracture; Testosterone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Body Composition / physiology
  • Bone Density / physiology*
  • Dihydrotestosterone / blood*
  • Femur / diagnostic imaging
  • Hip Fractures / epidemiology*
  • Hip Fractures / metabolism
  • Hip Joint / diagnostic imaging
  • Humans
  • Incidence
  • Male
  • Prospective Studies
  • Risk
  • Sex Hormone-Binding Globulin / metabolism
  • Tandem Mass Spectrometry
  • Testosterone / blood*

Substances

  • Sex Hormone-Binding Globulin
  • Dihydrotestosterone
  • Testosterone