Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women

J Clin Endocrinol Metab. 2008 May;93(5):1796-803. doi: 10.1210/jc.2007-2358. Epub 2008 Mar 11.


Context: Endogenous estradiol, testosterone, and SHBG may influence the risk of hip fracture.

Design and methods: From the Women's Health Initiative Observational Study, 39,793 eligible postmenopausal women did not have a previous hip fracture and were not using estrogen or other bone-active therapies. Of these, 400 who had a first-time nonpathological hip fracture (median follow-up, 7 yr) were matched to 400 controls by age, ethnicity, and baseline blood draw date. Estradiol, testosterone, and SHBG were measured in banked baseline serum.

Results: Compared with women in the lowest tertiles, those with bioavailable testosterone in the highest tertile had a lower risk [odds ratio (OR) = 0.62; 95% confidence interval (CI) = 0.44-0.88]; those with bioavailable estradiol in the highest tertile had a lower risk (OR = 0.44; 95% CI = 0.29-0.66), and those with SHBG in the highest tertile had a higher risk (OR = 1.90; 95% CI = 1.31-2.74) of hip fracture. In models with all three hormones and potential confounders, high SHBG remained a strong independent risk factor (OR = 1.76; 95% CI = 1.12-2.78), high bioavailable testosterone remained protective (OR = 0.64; 95% CI = 0.40-1.00), but estradiol no longer was associated (OR = 0.72; 95% CI = 0.42-1.23).

Conclusions: High serum SHBG is associated with an increased risk of subsequent hip fracture and high endogenous testosterone with a decreased risk, independent of each other, serum estradiol concentration, and other putative risk factors. But endogenous estradiol has no independent association with hip fracture.

Publication types

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

MeSH terms

  • Aged
  • Bone Density
  • Female
  • Gonadal Steroid Hormones / blood*
  • Hip Fractures / blood
  • Hip Fractures / etiology*
  • Humans
  • Middle Aged
  • Postmenopause / blood*
  • Risk Factors
  • Sex Hormone-Binding Globulin / analysis*


  • Gonadal Steroid Hormones
  • Sex Hormone-Binding Globulin