Fall, fracture risk may be increased with prostate-selective alpha antagonists in older men

Men 66 years of age and older who had filled a first outpatient prescription for tamsulosin, alfuzosin, or silodosin were compared with men who had not.

Older men who begin taking prostate-selective alpha antagonists may have an increased risk for falls and fractures, according to a new study.

Researchers performed a cohort study using patient-level data in Ontario, Canada, to compare men 66 years of age and older who had filled a first outpatient prescription for 1 of 3 prostate-specific alpha antagonists (tamsulosin, alfuzosin, or silodosin) between June 2003 and December 2013 with men who had not started such therapy. The study's primary outcome was an ED visit or inpatient admission for fall or fracture within the first 90 days of starting 1 of the 3 drugs. The results of the study were published online Oct. 26 by BMJ.

The study involved 147,084 matched pairs of men who had filled a prescription for a prostate-selective alpha antagonist and those who had not. The median age of all men was 75 years. Eighty-four percent of men in the drug cohort were prescribed tamsulosin, 14% were prescribed alfuzosin, and 2% were prescribed silodosin. More than half (54%) of prescriptions were from a primary care physician.

The researchers found that men who had been prescribed a prostate-specific alpha antagonist had significantly higher risk for falling (odds ratio, 1.14 [95% CI, 1.07 to 1.21]; absolute risk increase, 0.17% [95% CI, 0.08% to 0.25%]) and fracture (odds ratio, 1.16 [95% CI, 1.04 to 1.29]; absolute risk increase, 0.06% [95% CI, 0.02% to 0.11%]) in the first 90 days of therapy than those who had not. Men who were prescribed a prostate-specific alpha antagonist were also more likely to have hypotension (odds ratio, 1.80; 95% CI, 1.59 to 2.03) and head trauma (odds ratio, 1.15; 95% CI, 1.04 to 1.27) than those who were not, although no significant difference was seen in major osteoporotic fracture (odds ratio, 1.05; 95% CI, 0.89 to 1.23) or hip fracture (odds ratio, 0.98; 95% CI, 0.78 to 1.21).

The authors noted that unmeasured confounders could have affected their results, that drug adherence could not be measured, and that their study involved only men age 66 and older who were primarily taking tamsulosin, possibly limiting the results' generalizability. However, they concluded that older men taking prostate-specific alpha antagonists for lower urinary tract symptoms may have a higher risk for fall or fracture in the 90 days after starting treatment.

The authors of an accompanying editorial agreed that residual confounding was an issue and pointed out that effects beyond 90 days were not studied, that no increased risk for major fractures was noted, and that the absolute risk increase was small. They recommended that physicians tell patients that lower urinary tract symptoms are benign and attempt to address existing conditions, medications, and lifestyle factors that could be contributing.

The editorialists said treatment with a selective or nonselective alpha antagonist would be reasonable in patients who continue to experience “moderate bother” after lifestyle factors have been addressed, as long as the benefits are considered to outweigh the harms. 5-alpha reductase inhibitors could be added in some cases where symptoms progress, and surgery or treatments that are minimally invasive may be warranted in some cases based on lack of effect with medical therapy or patient preference, they said.

The editorialists described the study findings as “likely to be real, rare, and relevant” and recommended further study on the issue. Until more research is done, they wrote, “[T]he optimal balance of benefits, harms, and costs of α antagonists in older men with [lower urinary tract symptoms] will be primarily driven by patient factors including symptom bother.”