LAUSR

The NIDDK recently sponsored a 7‐week virtual seminar series titled: “Female Urethral Function and Failure: Advancing Basic and Translational Research for Genitourinary Conditions.” In this multinational consultation, recent evidence revealing the key role played by the urethra was discussed, the state of urethral knowledge evaluated, and important knowledge gaps in our understanding this critical organ identified. An executive summary of the series, as well as key points and identified research gaps, are available as Supporting Information. This international gathering of scientists underscored the need to re‐evaluate the current two‐factor theory that emphasizes abnormal detrusor function for urgency urinary incontinence (UUI) and poor urethral support for stress urinary incontinence (SUI) and to move to a three‐factor theory that includes the role that urethral failure plays in both stress and urge incontinence (Figure 1). If the urethra is critical to maintaining continence, then the question becomes, “now what?” Why has the urethra escaped scientific scrutiny for so long? It is probably because the widely held two‐factor theory of incontinence paralleled the treatments we had available at the time. However, starting in the 1960s evidence began accumulating that urethral function was much lower in incontinent women and many studies of this parameter followed. However, the fact that urethral support operations for SUI were reasonably successful without changing urethral pressure and the fact that measuring urethral pressure did not change outcomes led to the false assumption that urethral failure was not clinically important. Similarly, UUI is strongly associated in our minds with detrusor overactivity (i.e., bladder dysfunction), despite observations that involuntary detrusor contractions occur regularly in continent asymptomatic women while the bladder is filling and a failure to reliably demonstrate detrusor overactivity in women with UUI. However, despite the enigmatic nature of detrusor overactivity, bladder‐ specific treatments (e.g., anticholinergics, B3‐agonists, Botox) do reduce UUI episodes, at least partially. Continued belief in the theory that SUI was caused by poor support, and UUI by detrusor overactivity, and that the urethra did not play a role, is an example of what Nobel Prize winning psychologist Daniel Kahneman described “theory induced blindness” wherein we discount our observations when they disagree with a theory we believe. In this way, our two‐factor theory blinded us to the data showing the role of urethral function in incontinence. In addition, because we did not have interventions to increase urethral closure pressures, making a measurement to identify something you could not treat seemed futile. Ironically, it should have been obvious, even to lay people, that an organ's sphincter would play a role in holding fluid in. Now that treatment success based on the two‐factor theory has plateaued and is not