Estradiol and Testosterone vs. Bone Fractures in Women

The study shows that higher levels of estradiol (E2>0.82 ng/dL) and testosterone (T>13.3 ng/dL) are associated with lower chance of non-vertebral fractures. Risk reduction was as low as 44%. Should postmenopausal women be risk stratified by measuring serum E2 and T levels?



J   C   E   M

Case-Control Study

May 2017

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity.

Design and Setting: We performed a nested case-control study within the prospective Women’s Health Initiative Observational Study. Incident non-spine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen.

One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone–binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone.


In multivariable and race/ethnicity-adjusted models, higher estradiol (>8.25 pg/mL) and higher testosterone (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; P trend = 0.001 and OR, 0.76; P trend = 0.02, respectively). The interaction term between race/ethnicity and either estradiol or testosterone was not significant. There was no association between SHBG and fracture risk.

In models stratifying by race/ethnicity, higher estradiol was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36-0.87) and black women (OR, 0.61; 95% CI, 0.39-0.96).

Higher testosterone was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), Ptrend = 0.03.


Serum estradiol and testosterone are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.