Prodrome and Non-prodrome Phenotypes of Bladder Pain Syndrome/Interstitial Cystitis

To test the hypothesis that risk factors for bladder pain syndrome/interstitial cystitis (BPS/IC) in women differ between those with and without the BPS/IC prodrome.

Incident cases of BPS/IC and healthy controls were recruited nationally. More than half the BPS/IC cases reported subsyndromal urinary symptoms for decades before onset of BPS/IC and were identified as having the prodrome. Risk factors for BPS/IC were examined separately for cases with and without the prodrome using a set of matched controls.

Two risk factors distinguished 178 prodrome from 134 non-prodrome cases. One was "UTIs" in the year before BPS/IC onset, possibly a manifestation of the prodrome itself. The other was the presence of the maximal number of nonbladder syndromes (NBSs): prodrome cases were 12 times more likely than non-prodrome cases to have ≥4 NBSs. Additional risk factors for prodrome and/or non-prodrome cases were the direct association of exogenous female hormones, as well as 3 inverse associations: type 2 diabetes mellitus, multiple pregnancies, and current daily smoking.

Prodrome cases developed urinary symptoms in their early 20s (ie, the prodrome) and were at very high risk of numerous NBSs. Non-prodrome cases developed urinary symptoms in their early 40s (ie, full-blown BPS/IC) and were no more likely than controls to have the maximal number of NBSs. These findings are consistent with recent suggestions of two BPS/IC phenotypes: one with systemic and psychosocial manifestations and the other more specific to the bladder. Additionally, several risk factors identified here might be hints of related or causal nervous system pathophysiologies.