Long-Term Safety of Overactive Bladder Medications in Men Receiving Pharmacotherapy for Benign Prostatic Enlargement: A Real-World Study Using Inverse Probability of Treatment Weighting

For many aging men, lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE) are not limited to voiding difficulties; storage symptoms such as urgency and frequency often significantly impair quality of life. While international guidelines suggest that adding overactive bladder (OAB) medications (antimuscarinics or β3-adrenoceptor agonists) can be effective for persistent storage symptoms, a significant "prescription gap" remains in clinical practice. Many clinicians hesitate to prescribe these agents due to a long-standing fear of inducing acute urinary retention (AUR) or worsening post-void residual (PVR) volume.

Randomized controlled trials (RCTs) have generally demonstrated the safety of these combination therapies. However, RCTs often operate under "ideal" conditions, frequently excluding high-risk patients such as those with significant baseline PVR or a prior history of urinary retention. Consequently, it has remained unclear whether these safety profiles are truly generalizable to the broader, more heterogeneous populations we see in daily urological practice. Our study sought to address this gap by evaluating the long-term safety of OAB medications in a real-world BPE cohort.

One of the most important findings of our study was the substantial selection bias observed in real-world prescribing patterns. Patients who were prescribed OAB medications tended to have smaller prostate volumes, lower PSA levels, and lower baseline PVR compared to those who were not. In other words, physicians were already intuitively selecting "safer" candidates for OAB therapy. To account for this inherent selection bias and provide a fair comparison, we utilized inverse probability of treatment weighting (IPTW) based on propensity scores. This statistical approach allowed us to simulate a balanced comparison, effectively adjusting for baseline differences between OAB medication users and non-users.
With a median follow-up of 28.7 months, our analysis yielded several critical insights:

After IPTW adjustment, the addition of OAB medications was not associated with an increased risk of AUR (Hazard Ratio 1.18; 95% CI 0.38-3.62; p = 0.776). This provides reassurance that combination therapy is reasonably safe for long-term use when managed by specialist clinicians.
While overall safety was high, we identified a specific subset requiring closer attention. Among patients receiving OAB drugs, a history of AUR at presentation (iAUR) was a significant predictor of treatment discontinuation due to increased PVR (Hazard Ratio 9.10; 95% CI 1.81-45.6; p = 0.01).
Despite 66.5% of patients meeting the diagnostic criteria for OAB based on OABSS, only 23.5% received OAB-specific drugs. This underscores a persistent caution among providers that may be limiting optimal symptom control for many patients.

Our findings suggest that the clinical "caution" often exercised by urologists is effective, but perhaps overly restrictive. While combination therapy does not markedly increase the risk of AUR in a general BPE population, those with a history of urinary retention are at a nearly nine-fold higher risk of voiding deterioration when starting OAB medications. For the practicing urologist, the takeaway is clear: OAB medications can be safely integrated into the long-term management of BPE-related storage symptoms, provided that patients with a history of AUR are monitored with extra vigilance. By bridging the gap between guideline recommendations and real-world practice, we can better optimize the quality of life for our patients without compromising their safety.

Written by: Takeshi Soda, Tomoaki Yamauchi, Hikari Otsuka, Yuki Makino, Takuya Okada

Department of Urology, Medical Research Institute Kitano Hospital, Kita-Ku, Osaka, Japan.

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