Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To review key trials of monotherapy and combination therapy of alpha(1)-adrenergic receptor antagonists (alpha(1)-ARAs), 5alpha-reductase inhibitors (5alphaRIs) and anti-muscarinic agents in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the safety and efficacy of combination therapies for LUTS associated with BPH, a search of the MEDLINE and Cochrane databases (1976-2008) was conducted for relevant trials and reviews using the terms benign prostatic hyperplasia, lower urinary tract symptoms, alpha(1)-adrenergic receptor antagonists, 5alpha-reductase inhibitors, anti-muscarinics, anticholinergics, combination therapy, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, tolterodine, flavoxate, propiverine, oxybutynin, erectile dysfunction, sildenafil, vardenafil and tadalafil. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study indicated a role for long-term use of alpha(1)-ARAs and 5alphaRIs in combination. In the MTOPS study, combination therapy with the alpha(1)-ARA doxazosin and the 5alphaRI finasteride was significantly more effective than either component alone in reducing symptoms (P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and in lowering the rate of clinical progression (P<0.001 vs either monotherapy). These findings were confirmed by the 2-year preliminary results of the Combination of Avodart and Tamsulosin study. In this study, combination therapy of the alpha(1)-ARA tamsulosin and the 5alphaRI dutasteride resulted in a significantly greater decrease in International Prostate Symptom Score (IPSS) when compared with either monotherapy. Several recent trials have studied the efficacy of combining alpha(1)-ARAs and anti-muscarinic agents in the treatment of BPH. These studies have found this combination to result in statistically significant benefits in quality of life scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores. Studies have not shown an increased risk of urinary retention associated with the use of anti-muscarinics in a highly select cohort of men with BPH. The available data suggest that combination therapy can be beneficial in the treatment of BPH and associated LUTS. The greatest efficacy for the alpha(1)-ARA and 5alphaRI combination was shown in patients with larger prostate size and more severe symptoms. The combination of alpha(1)-ARAs and 5alphaRIs appears to prevent disease progression in these patients. The combination of alpha(1)-ARAs with anti-muscarinic agents is useful for relieving symptoms of bladder outlet obstruction and detrusor overactivity. Theoretic concerns regarding the risk of acute urinary retention have been refuted in several recent clinical trials; however, it must be noted that the patients in these trials were a highly select cohort of men. Men with overactive bladder and BPH who are not receiving adequate alleviation of symptoms from the first-line alpha(1)-ARAs may benefit from the addition of an anti-muscarinic agent.
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PMID:The role of combination medical therapy in benign prostatic hyperplasia. 1900 23

OBJECTIVES To evaluate the number of medical and urological conditions associated with nocturia in a cohort of older men who were primary-care enrolees, and to assess the feasibility and efficacy of using a multicomponent intervention to reduce nocturia and its bother. SUBJECTS AND METHODS Men aged > or =50 years and with two or more episodes of nocturia were recruited from the primary-care clinics at one Veterans Affairs Medical Center to participate in a 4-week, open-label, prospective pilot study. A multicomponent intervention composed of behavioural therapy and targeted drug therapy was administered according to a specified protocol based upon identified risk factors for nocturia. Outcome measures included self-reported nocturia and bother on the American Urological Association (AUA)-7 Symptom Index, 3-day bladder diaries and self-reported sleep-related measures recorded using 7-day sleep diaries. RESULTS Fifty-five men completed the protocol (mean age 67 years, sd 8.3); they had a mean of 4.5 of nine defined conditions potentially related to nocturia. Highly prevalent conditions included moderate-to-severe benign prostatic hyperplasia (87%), hypertension (86%) and urinary frequency (71%). The mean diary-recorded nocturia decreased from 2.6 to 1.9 (P < 0.001), and bother score reduced from 3.1 to 1.1, representing a change from a 'medium' to a 'very small' problem (on a 5-point scale). Sleep diary-derived measures also improved significantly (time to initiate sleep, time to return to sleep after awakening, quality of sleep). CONCLUSIONS Given that individual older patients often have multiple coexistent risk factors for nocturia, identifying a principal cause of nocturia, a concept emphasized in treatment guidelines, proved to be difficult. Implementing a multicomponent behavioural intervention combined with drug(s) was feasible in older men and reduced nocturia frequency, bother from nocturia, and time to initiate sleep, within 4 weeks. These promising results merit repeating using a randomized, controlled trial.
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PMID:A multicomponent behavioural and drug intervention for nocturia in elderly men: rationale and pilot results. 1922 Feb 47