Sex Hormones and the Risk for Hip Fracture in Men

Hip fractures in men result in significant morbidity and mortality. In fact, the 1-year mortality rate after hip fracture in men is twice that in women. Understanding risk factors among older men will allow physicians to identify those who may require intervention to prevent hip fracture.

What problem was studied?
It is well known that in women, estrogen levels decrease at menopause and that this decrease leads to a decrease in bone mineral density and an increase in fracture risk. Although the predominant sex hormone in men is testosterone, men do produce estrogens (estradiol being the most prevalent and bioactive) that have an effect on bone health. It is not well understood, however, how sex hormone levels in men affect fracture risk.

Using the Framingham cohort, Arthritis Foundation-funded researchers Shreyasee Amin, MDCM, MPH, who is currently at the Mayo College of Medicine, and David T. Felson, MD, MPH, of Boston University School of Medicine, and others from Boston University, the Department of Veterans Affairs, Harvard Medical School, and the National Heart, Lung and Blood Institute studied estradiol and testosterone levels in elderly men who endured hip fracture.

What was done in the study?
Sex steroid hormones were first measured in male participants of the Framingham study in 1981–1983. The researchers studied 793 men who participated in those examinations and met other eligibility criteria. During each biennial examination, participants were queried about any fractures and hospitalizations. Through records of these interviews and exams, hip fractures were systematically identified. Fractures were designated traumatic or atraumatic; only atraumatic hip fractures (occurring after a fall from a standing height or less) were analyzed, as these types of fractures are more likely to be related to osteoporosis. The relationship between sex hormone levels and fracture occurrence was assessed.

What were the study results?
Over the 18-year follow-up period, 39 men had an atraumatic hip fracture. Compared with those who did not sustain a hip fracture, those who did were older, had a lower body mass index, and had lower sex hormone levels at baseline; they were similar in height and smoking status.

The men were categorized according to their estradiol level: 120 men were in the low group; 358 were in the middle group; and 315 were in the high group. After adjustment for age, body mass index, height and smoking status, men in the low estradiol group had 3 times the risk of hip fracture compared with men in the high estradiol group. The men were also categorized according to their testosterone level: 173 men were in the low group, 281 in the middle group and 338 in the high group. After adjustment for age, body mass index, height and smoking status, men in the low testosterone group had just under a 2-fold increased risk for hip fracture, but it was not statistically significant.

Furthermore, in similarly adjusted analyses where levels of both hormones together in men were considered, it was found that men who had both low estradiol and low testosterone levels had the greatest risk of hip fracture. That result indicates there may be a synergistic effect on the risk for hip fracture when both hormone levels are low.

What does this mean to elderly men?
This study, combined with others, increases our understanding of the important role of estrogens on male bone health. Such information will improve physicians’ ability to better identify those at greatest risk so that preventive intervention can be considered (medications to prevent bone loss, fall prevention strategies, etc.) and new drug treatments can be developed. Further work is still necessary on the best strategy to screen men for low estradiol levels.

Amin S, Zhang Y, Felson DT, et al. Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham study. Am J Med 2006;119:426-33.