A novel approach to management of nocturia in patients with benign prostatic hyperplasia.

SUMMARY

The authors in this prospective, randomized, double-blind, placebo-controlled study have assessed the usefulness of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in the management of refractory nocturia in patients with benign prostatic hyperplasia (BPH). A total of 80 patients with BPH who had ≥2 voids per night, prostate volume >20 cm3, an international prostate symptom score (IPSS) of ≥8, and whose nocturia had not responded to α-blockers and 5α-reductase inhibitors (which was given if prostate volume was >30 cm3) were included and randomized into two groups. Patients in the celecoxib group received 100 mg of celecoxib once daily while those in the control group received a similar looking placebo. The drugs were given at 9 pm for a period of 1 month. Prior to accruing patients into the study, coexisting urinary tract infection (UTI) or carcinoma of the prostate were excluded. Post intervention response to treatment, at the end of 1 month, was assessed and reported as excellent (nocturia disappeared or decreased by ≥2 voids/night), improved (nocturia decreased by 1 void/night), or unchanged. Other parameters assessed include IPSS, peak flow rate, and side-effect profile of celecoxib. The data was analysed using a paired t-test.

Both the control and celecoxib groups had comparable mean age, prostate size, peak flow rates, IPSS score, and nocturia prior to the intervention. The authors found that the mean number of nocturia episodes decreased significantly in the celecoxib group (P < 0.0001). The percent of patients with an excellent response was 70% in the celecoxib group and 7.5% in the placebo group. The change in the peak flow rate was not statistically different between the two groups. None of the 80 patients discontinued treatment because of drug-related side-effects. The authors concluded that celecoxib was an effective treatment option for patients with BPH with nocturia.[1]

COMMENTS

Nocturia (having to wake up at night one or more times to void), the most prevalent symptom of BPH, is not only associated with complaints of insufficient sleep, decreased quality-of-life, and decreased productivity at work, but it also may result in nighttime falls with potentially serious consequences like fractures, etc. Medical therapy for BPH is able to decrease this symptom by more than 50% in only 25-39% of patients, leaving a lot to be desired.[2]

Prostaglandins (PGs), by virtue of their action on the afferent arteriole of the kidney and on the detrusor muscle[3] of the bladder are said to have a role in the pathogenesis of nocturia. Prostaglandins cause vasodilatation of the afferent arteriole resulting in an increase in the glomerular filtration rate and ultimately in the amount of urine produced. Further, prostaglandins E and F increase the tone of the detrusor muscle and enhance micturition.

The above-mentioned role of prostaglandins forms the basis of the use of non steroidal anti inflammatory drugs (NSAIDs) in the treatment of nocturia in patients in whom this symptom is poorly controlled by medical therapy prescribed for BPH. NSAIDs block the COX-1 and COX-2 enzymes, which convert arachidonic acid to prostaglandins. Reduced prostaglandin synthesis, in part explains the clinical benefit that is seen with this class of drugs.

Another additional benefit that NSAIDs may provide in patients with BPH is that by virtue of their anti inflammatory properties, the pathogenesis of BPH may be altered in a positive fashion since chronic inflammation is believed to be an etiological factor in patients with BPH. Studies have shown that focal upregulation of COX-2 takes place in the glandular epithelium of patients with BPH.[4]

Previously, non randomized observational studies have found NSAIDs like loxoprofen to be clinically effective in patients with BPH with nocturia.[5]

The authors in this study performed a randomized, controlled trial comparing the effect of celecoxib with placebo in the treatment of nocturia and found celecoxib to be effective in the treatment of nocturia due to BPH. However, since the study population was small and the study period short, larger studies addressing this issue are needed before celecoxib use in patients with BPH with nocturia can be advocated in routine clinical practice.