Both short- and long-acting inhaled anticholinergic medications appear to raise the risk of acute urinary retention in men taking the drugs for treatment of chronic obstructive pulmonary disease, according to a report in the May 23 issue of the Archives of Internal Medicine.
Men who take both types of anticholinergics concomitantly and men who have benign prostatic hypertrophy (BPH) are at highest risk for developing acute urinary retention, which is considered a urologic emergency, said Dr. Anne Stephenson of St. Michael’s Hospital, Toronto, and her associates.
"Physicians and the public need to be aware of the potential for this significant adverse event so that preventive measures and potential therapy can be considered," they said.
Until now, it has been "uncertain" whether inhaled anticholinergics caused detrimental urologic effects. Canadian, European, and American practice guidelines say little about possible adverse effects on prostatic symptoms, and clinical studies offer conflicting results.
To examine the association between exposure to inhaled anticholinergics and the development of acute urinary retention, Dr. Stephenson and her colleagues performed a population-based case-control study, first identifying all 563,705 Ontario residents aged 66 years and older who had COPD and whose records could be followed in a medical database for a median of 5 years.
During that time, 9,432 of the men and 1,806 of the women developed a first episode of acute urinary retention. These cases were matched with 46,865 men and 9,020 women with COPD who did not develop acute urinary retention and served as control subjects.
Men who used inhaled anticholinergics were at significantly increased risk of developing acute urinary retention, but women were not.
Men who initiated inhaled anticholinergic therapy during the study period had more than a 40% higher chance of developing acute urinary retention than were men who didn’t use the drugs. This was true with either short-acting agents (ipratropium products) or a long-acting agent (tiotropium bromide).
Men who initiated combination therapy with both short- and long-acting inhaled anticholinergics were at 169% higher risk than were those who didn’t take the drugs, suggesting a dose-response relationship.
Men who were already taking inhaled anticholinergics at baseline rather than initiating the therapy were at slightly lower but still significantly increased risk of developing acute urinary retention, with an odds ratio of 1.36.
Men with BPH who began taking the drugs had an 80% greater chance of developing acute urinary retention, compared with nonusers. "According to our risk estimates, for men with BPH newly initiating a regimen of inhaled anticholinergics, 1 in 514 will experience this adverse event," the investigators said (Arch. Intern. Med. 2011;171:914-20).
Among new users of the drugs, acute urinary retention tended to develop within 30 days (median, 14 days), "further strengthening a causal relationship.
"These data suggest that [patients] may benefit from close monitoring for signs and symptoms of impending urinary retention within the first month of starting inhaled anticholinergics," they said.
Moreover, any patient taking these drugs who develops urinary changes should be carefully evaluated for possible preventive or therapeutic interventions, Dr. Stephenson and her associates added.
"We suggest that the association between respiratory inhaler use and bladder dysfunction may be underappreciated by the medical profession and by the public. ... Physicians should highlight for patients the possible connection" to urinary symptoms such as incomplete voiding, urinary incontinence, and decreased urinary flow.
This study was somewhat limited in that there were no data available on patient-related variables such as lung function, smoking history, renal impairment, and severity of COPD, all of which could be confounders.
"The lack of effect among women ... could be a reflection of the small sample size within this subgroup." Also, women are known to have substantially lower rates of urinary retention than men, most likely because of anatomical differences in the urinary tract.
Dr. Stephenson’s study was funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care. No financial conflicts of interest were reported.