Relationship Between Depression and Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

This article provides an overview of current data on the relationship between depression and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), with a focus on pathophysiology and patient management implications. Review of the literature indicated a clear relationship between LUTS secondary to BPH and depression. It is unknown whether this relationship is bidirectional or unidirectional. Depression is associated with the impact of LUTS on quality of life in men with BPH. Research suggests that depression alters the experience of LUTS in this population. Medical and surgical treatments for BPH may impact quality of life and, therefore, depression. Results conflict on the exact nature of the relationship examined, and on the extent to which the relationship may be attributed to physiological factors such as inflammation. Practicing clinicians should consider using a brief self-administered scale to assess for depression in patients with BPH. There is a clear need for additional research to decisively determine the nature of the relationship between LUTS secondary to BPH and depression, as well as the extent to which change in either condition may be affected by the other.Key words: Benign prostatic hyperplasia, Depression, Lower urinary tract symptomsThe prevalence of benign prostatic hyperplasia (BPH) increases with age.¹ Approximately half of men over age 40 are diagnosed with BPH. Of these men, approximately 50% will develop significant and bothersome lower urinary tract symptoms (LUTS) secondary to BPH, which increase in prevalence between ages 40 and 80 years. LUTS secondary to BPH is associated with decreased quality of life and may include urgency/frequency, incontinence, and nocturia. Symptom severity is impacted by the degree of prostatic enlargement, which is highly variable.¹Depression is another common condition that severely and negatively impacts quality of life, with an estimated lifetime prevalence of 16.5% according to the National Institute of Mental Health.² Depression plays a role in the pathogenesis of a number of chronic diseases, including inflammatory bowel disease, arthritis, asthma, and diabetes³; a relationship has also been identified between depression and urologic diagnoses such as incontinence.⁴ Symptoms of BPH are associated with decreased quality of life and depression, and the literature strongly suggests that there may also be a pathophysiologic relationship between BPH and depression^5,6; in addition, depressive symptoms are also associated with treatments for BPH.^7–9Research has suggested that psychiatric parameters such as depression may have a putative role in the development of LUTS secondary to BPH.⁶ Furthermore, depression may pose an impediment to effective treatment for these patients. Improved understanding of the relationship between BPH and depression could lead to improved management. This area of research is important because clinical depression is associated with a significant increase in mortality, and early detection, intervention, and treatment of clinically relevant depressive symptoms are key factors in patient care.¹⁰Fewer studies have focused on the relationship between depressive symptoms or depressive disorders and BPH, or the nature and direction of this relationship. Thus, a systematic review of the relationship between depression and BPH is needed. We provide a comprehensive summary of contemporary published reports on LUTS secondary to BPH and depression to improve understanding of the relationship between these two conditions and provide a framework for future investigation.     

Increased Serum C-Reactive Protein Level Is Associated with Increased Storage Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Objective

Chronic inflammation is considered as one of the contributing mechanisms of lower urinary tract symptoms (LUTS). Serum C-reactive protein (CRP) level is the widely used biomarker of inflammatory status. This study investigated the association between serum CRP level in men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) before and after medical treatment.

Methods

A total of 853 men with BPH and LUTS were enrolled. All patients completed the International Prostate Symptoms Score (IPSS) questionnaire and urological examinations. The parameters of uroflowmetry (maximum flow rate, Qmax; voided volume, VV), post-void residual (PVR), total prostate volume (TPV) and transition zone index (TZI), serum prostate specific antigen (PSA), and serum CRP levels were obtained. All patients were treated with alpha-blocker or antimuscarinic agent based on the IPSS voiding to storage subscore ratio (IPSS-V/S). Correlation analyses were performed between serum CRP levels with age, IPSS, TPV, TZI, Qmax, PVR, VV, PSA and between baseline and post treatment.

Results

The mean age was 66.9±11.6 years old and the mean serum CRP levels were 0.31±0.43 mg/dL. Univariate analyses revealed serum CRP levels were significantly associated with age (p<0.001), PSA levels (p = 0.005) and VV (p = 0.017), but not significantly associated with TPV (p = 0.854) or PVR (p = 0.068). CRP levels were positively associated with urgency (p<0.001) and nocturia (p<0.001) subscore of IPSS, total IPSS (p = 0.008) and storage IPSS (p<0.001) and negatively associated with IPSS- V/S ratio (p = 0.014). Multivariate analyses revealed that serum CRP levels were significantly associated with age (p = 0.004) and storage IPSS subscore p<0.001). Patients with IPSS-V/S<1 and treated with tolterodine for 3 months had significant decrease of CRP levels after treatment.

Conclusion

Serum CRP levels are associated with storage LUTS and sensory bladder disorders, suggesting chronic inflammation might play a role in the patients with storage predominant LUTS.     

Comparative Effectiveness of Oral Drug Therapies for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis

Introduction

Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.

Materials and Methods

An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs) comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.

Results

A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs) plus phosphodiesterase 5 inhibitors (PDE5-Is) ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax) with a mean difference (MD) of 1.98 (95% CI, 1.12 to 2.86) as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs) ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.

Conclusions

Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other pharmacologic agents alleviate the symptoms of LUTS/BPH.     

(Arylpiperazinyl)cyclohexylsufonamides: discovery of alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS)

Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1) blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited.