Lower urinary tract disease: what are we trying to treat and in whom?
The diseases of the lower urinary tract are traditionally divided into abnormalities of storage and abnormalities of emptying. The targets for therapy were the organs most responsible for influencing storage and emptying. Modern understanding places the symptomatic status of the patient as the overriding criterion for treatment. It also accommodates a broader understanding of multiple and overlapping systems. Symptoms of voiding dysfunction have been clearly shown to be associated with symptoms of other genitourinary disease, for example, erectile dysfunction (ED). Treatment of voiding dysfunction has also been shown to have effects (adverse or beneficial) in these other domains. Thus, the symptoms of lower urinary tract disease (LUTD) that have to be considered now as targets relevant to these therapies include ED, ejaculatory dysfunction, sexual desire, sexual pain disorders and female sexual dysfunction. The anatomic, neural and endocrine systems that support these symptomatic functions and dysfunctions span the range from the urogenital smooth muscle to the hypothalamus, the bladder sensory output to the micturition centre and growth factors to androgens. Potentially important targets also include vascular and spinal structures, sex hormones and nitric oxide as well as the obvious genes, enzymes and receptors. The epidemiological studies prove the convergence of LUTD when viewed through the lens of the current patient-related outcomes and problem constructs. This convergence serves as a clear guidance to include wide ranging outcome instruments in all future studies with compounds being investigated for the treatment of LUTD. Out of these will come evidence of expected and unexpected collateral effects. The convergence should open the possibility to a different business model for developing therapeutic concepts. The blockbuster drug for a monolithic indication may be supplemented by agents with single or multiple pathway activity with smaller parallel targets. Using an approach based on patient reported outcomes to therapeutic targets not only widens the range of conditions, but also the patient types who can be considered as having LUTD.
Heaton
Jeremy P W
JP
Queen's University, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7. heatonj@btconnect.com
D003863:Depression / Q000150:complications / Q000453:epidemiology; D007172:Erectile Dysfunction / Q000150:complications / Q000453:epidemiology; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D015995:Prevalence; D011470:Prostatic Hyperplasia / Q000150:complications / Q000453:epidemiology; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D001745:Urinary Bladder Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000628:therapy; D053201:Urinary Bladder, Overactive / Q000453:epidemiology / Q000209:etiology; D014549:Urinary Incontinence / Q000453:epidemiology / Q000209:etiology; D014555:Urination Disorders / Q000453:epidemiology* / Q000209:etiology* / Q000628:therapy