News Author: Emma Hitt, PhD

May 1, 2006 — Low serum estradiol levels in men may be associated with an increased risk for low-trauma hip fracture, and risk may be even greater for those who also have low testosterone levels, according to the findings of a new analysis in the May issue of The American Journal of Medicine.

The analysis, led by Shreyasee Amin, MD, now with the Mayo Clinic in Rochester, Minn, included 793 men from the National Heart, Lung, and Blood Institute's Framingham Heart Study http://www.framingham.com/heart.

Participants included in the analysis had undergone measurement of their estradiol and testosterone levels between 1981 and 1983. Participants had no prior hip fracture and were followed until 1999.

Estradiol levels were classified as low (2.0 - 18.1 pg/mL), medium (18.2 - 34.2 pg/mL), or high (>/= 34.3 pg/mL). The researchers also distinguished between high-trauma and low-trauma hip fractures. An example of a low-trauma fracture would be one that resulted from a fall from a standing height or less.

The hazard ratio (HR) was adjusted for age, body mass index, height, and smoking status. For men in the low estradiol group relative to the high estradiol group, the HR was 3.1 (95% confidence interval [CI], 1.4 - 6.9). No difference in risk was observed for medium- vs high-level groups (HR, 0.9; 95% CI, 0.4 - 2.0).

"The smoothed dose-response curve also suggested that the increased risk for hip fracture exponentially changed below serum estradiol levels of roughly 20.0 pg/mL," the authors write.

Men were also evaluated on the basis of their testosterone levels. No difference in adjusted risk was found on the basis of testosterone levels alone. However, low testosterone levels in addition to low estradiol levels appeared to compound the risk of hip fracture (adjusted HR, 6.5; 95% CI, 2.9 - 14.3).

"While the key role of estradiol is increasingly recognized among researchers in bone metabolism, it is an under-recognized risk factor in clinical general medicine," the authors write.

"These findings add further evidence to the important role of estrogen in the bone health of older men," notes Dr Amin in a written release. "It's important for us to know what puts men at risk for hip fracture so that we can better determine how we may prevent these fractures."

The researchers note that further work is needed to validate the potential clinical application of these findings but that the "results also raise the novel possibility that low testosterone levels may have a synergistic effect with low estradiol levels on hip fracture risk."