Bladder Pain Syndrome/Interstitial Cystitis Linked to Statins

Regular and irregular use of the lipid-lowering medications increased the risk of BPS/IC.
Regular and irregular use of the lipid-lowering medications increased the risk of BPS/IC.

Statin use is associated with an increased risk of bladder pain syndrome/interstitial cystitis (BPS/IC), according to investigators in Taiwan.

Using the Taiwan Longitudinal Health Insurance Database (LHID), Li-Hsuan Wang, MD, and colleagues at Taipei Medical University compared 815 female patients with BPS/IC and 4,075 randomly selected female controls. After adjusting for numerous co-morbidities and other confounders, regular and irregular statin use were associated with a significant 58% and 53% increased odds of BPS/IC, respectively, the researchers reported in Urologia Internationalis (2015;95:227-232).

The researchers defined regular statin users as patients who had received continuous statin prescriptions for 60 days or more within 6 months prior to their index date (when patients made their first ambulatory visit to treat BPS/IC). Irregular users were all other subjects who had been prescribed statins within 6 months before the index date.

Dr. Wang's team identified regular statin use in 10.9% of BPS/IC patients compared with 7.2% of controls and irregular statin use in 4.3% of BPS/IC patients compared with 2.6% of controls.

The authors proposed possible explanations for the association between statin use and BPS/IC. They cited previous studies showing that simvastatin was more effective at inhibiting the growth of normal prostate epithelial cells than cancer cells (Eur J Pharmacol. 2011;673:96-100) and that lovastatin induced apoptosis in cultured prostate stromal cells from normal or benign prostatic hyperplasia (J Clin Endocrinol Metab. 1997;82:1434-1439). “We presume that statins also induce cell apoptosis and suppress cell growth in the urothelium of patients with BPS/IC.”

In addition, the authors pointed out that statins have immunomodulatory capabilities. Some studies have found that statins increase expressions of proinflammatory cytokines in immune cells, such as dendritic cells and macrophages. “Therefore, statin use may induce chronic inflammation in the bladder urothelium.”

Lastly, the investigators noted that “statins may cause neurogenic inflammation in the bladder urothelium that leads to abnormal bladder permeability and changes in bladder sensations.”

Study strengths included the use of a population-based dataset that enabled the tracing of all cases of BPS/IC during the study period, the authors stated. Also, the large sample size afforded a considerable statistical advantage in detecting the association between statin use and BPS/IC.

The researchers also acknowledged study limitations. For example, they were unable to evaluate the association between statin concentrations and the severity of BPS/IC. Furthermore, the LHID data did not include complete information on patients' social history (including their smoking and alcohol use patterns) and nonprescription medication use. Therefore, the investigators could not study the impact of those factors. Another limitation was the identification of BPS/IC diagnoses using administrative claims data reported by physicians and hospitals. “These may be less accurate than diagnoses made according to standardized criteria of the International Continence Society.”

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