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

Emily A. Rosenberg, Petra Bůžková, Howard A. Fink, John A. Robbins, Molly M. Shores, Alvin M. Matsumoto, Kenneth J. Mukamal

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number154399
JournalMetabolism: clinical and experimental
Volume114
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
This work was supported by 1R01HL091952 and contracts HHSN268201200036C , N01-HC-85239 , N01 HC-55222 , N01-HC-85079 , N01-HC-85080 , N01-HC-85081 , N01-HC-85082 , N01-HC-85083 , N01-HC-85086 , and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG-023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org . Additional support was provided by The Department of Veterans Affairs and the VA Puget Sound Health Care System .

Funding Information:
This study was funded by the National Heart, Lung, and Blood Institute (NHLBI) ( 1R01HL091952 , HHSN268201200036C , N01-HC-85239 , N01 HC-55222 , N01-HC-85079 , N01-HC-85080 , N01-HC-85081 , N01-HC-85082 , N01-HC-85083 , N01-HC-85086 , HL080295 ) and the National Institute on Aging ( AG-023629 ).

Keywords

  • Androgen
  • Bone mineral density
  • Dihydrotestosterone
  • Hip fracture
  • Testosterone

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