Medical Therapy for Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms.

Change in Sexual Function in Men with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Associated with Long-Term Treatment with Doxazosin, Finasteride and Combined Therapy

Medical and surgical therapies for benign prostatic hyperplasia (BPH) are based largely on the results from adherence to the 2003 American Urological Association Guidelines. However, with the emergenceof medical therapies as first-line treatment and the expansion of medical therapy for lower urinary tract symptoms (LUTS) into the primary care office, the evaluation and management of men presenting with urinary symptoms can vary depending on provider type. This review explains the basis for BPH medical management in primary care with the review of three key studies. In addition, this review utilizes the data provided by the first longitudinal, observational BPH registry to evaluate patient outcomes and practice patterns in both urologist and primary care offices. From these data, we can conclude that men seeing urologists were more likely to be on medical therapy than men seeing primary care physicians (PCPs), who more often utilized watchful waiting. Urologists also were more likely to prescribe 5-alpha-reductase inhibitors (5ARIs), combination therapy with an alpha-blocker and 5ARI, and anticholinergic therapy. In contrast, the use of nonselective alpha-blockerswas appreciably greater among men seeing PCPs than men seeing urologists.

The aim of this study is to examine how the introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) might have changed the indications, patient characteristics and outcome in men undergoing transurethral resection of the prostate (TURP) over two decades (1991.- 2011.). All patients who underwent TURP for symptomatic BPH at our institutions in 1991. (before the introduction of medical therapy for BPH), 2001. (when medical therapy was becoming an important therapy for BPH) and 2011. (when medical therapy was the first line therapy for BPH), were reviewed. We assessed the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and pre and post-operative events/ complications. Our institutions provided primary urological care for 989, 1815 and 2162 men > 50 years of age in 1991., 2001. and 2011., respectively. There was a 60% decrease of TURPs from 1991. to 2011. with a slight increase in number in 2001. Failure of medical therapy was not an indication in 37% and 88% of patients in 2001. and 2011., respectively. There was a substantial rise in the percentage of men at risk presenting with acute or chronic retention (AUR and CUR) at the time of their TURPs ( from 23% in 1991. to 55% in 2001. and from 14% in 1991. to 38% in 2011. for AUR and CUR, respectively) (P<0.05). There was also rise in the percentage of patients presenting with preoperative hydronephrosis (2% in 1991., 13% in 2001. and 6% in 2011.) (P<0.05) and gradual decrease of UTI before TURP overtime (14%, 10% and 12%, respectively).The mean operative time was lower in 2011., compared with either of the two previous cohorts (P<0.05), postoperative stays decreased (from 4.1 days in 1991. to 2.7 days in 2001. and 2.1 days in 2011.)(P<0.05), but the number of patients discharged with catheter increase over two decades (from 3.5% in 1991 to 4.8% in 2001., and to 8.8% in 2011.)(P<0.05). The postoperative complications of our three cohorts differed significantly (14% in 1991., 6.4% in 2001. and 20.6% in 2011.)(P<0.05). The increasing use of medical therapy as a first line treatment for BPH has resulted in a dramatic decrease in TURPs which, in turn, has been associated with an apparent increase in risk of poor pre- and postoperative outcomes seems to be related to earlier catheter removal and hospital discharge, although a causal relationship cannot be established. The present study covering the last two decades would suggest that we are not delaying surgery for patients who will eventually require it. We are now selecting the appropriate patients for TURP, rather than using TURP as our only means of BPH therapy as we did two decades ago.

Long-Term Effects of Doxazosin, Finasteride and Combination Therapy on Quality of Life in Men with Benign Prostatic Hyperplasia

Despite a large amount of literature focused on pharmacologic and surgical therapy for benign prostate hyperplasia (BPH), little is known about clinical presentation and management of outpatient clinic patients. We aimed to conduct a tailored analysis of BPH-affected patients, comparing men with known BPH versus newly diagnosed. The analysis was made through International Prostate Symptom Score (IPSS) and BPH Impact index (BII). "Intensive prostate benefit" project working group designed a questionnaire prospectively administered by urologists to patients affected by lower urinary tract symptoms (LUTS) related to BPH. Overall, 3198 (64%) patients were previously diagnosed with BPH versus 1800 (36%) received a first diagnosis. Patients previously diagnosed with BPH were older (median 69 vs. 66 years) and more comorbid (P<0.001). Moreover, median IPSS score was higher in these patients (16 vs. 14), who also experienced a higher rate of severe symptoms (32.0% vs 21.5%, P<0.0001). At BII, concerns for one's health and time lost due to urinary problems were higher in patients previously diagnosed with BPH (P<0.0001). In these patients, a BPH-specific therapy was already established (88.5% vs. 75.1%) and a higher rate of therapy adherence (55.0% vs. 27.0%, P<0.0001) was observed. Roughly 90% of patients already taking BPH therapy changed their therapy after urological examination. In these patients, supplements/phytotherapeutics, alpha blockers, 5-alfa-reductase inhibitors, were prescribed in 32.8%, 37.4%, 17.4%, respectively. Patients with prior BPH diagnosis have severe LUTS that worsen over time, affecting quality of life despite treatment. LUTS management in primary care is crucial, emphasizing counseling for a healthy lifestyle, cardiovascular risk control, and medication adherence.

Incidence and Progression of Lower Urinary Tract Symptoms in a Large Prospective Cohort of United States Men

Society of Interventional Radiology Research Reporting Standards for Prostatic Artery Embolization

The follow-up results, as well as own case study, are presented to evaluate the efficacy and tolerability of creeping palm fruit extract (Permixon) in combination with an α-blocker in patients with lower urinary tract symptoms (LUTS) of moderate severity associated with benign prostatic hyperplasia (BPH). The follow-up study involved 58 male patients aged 48 to 70 years (mean age 60.1±3.4 years). Group 1 (n=30) was assigned a combined therapy with Tamsulosin (alpha blocker) (0.4 mg once daily) and Permixon (1 capsule, 160 mg, twice daily) for 6 months. Group 2 (n=28) underwent monotherapy with Tamsulosin (0.4 mg once daily) also for 6 months. The observed patients underwent a comprehensive urological examination, which included an assessment of symptoms in points on IPSS (International Prostate Symptom Score); laboratory and instrumental studies. The patients were examined before and 3 and 6 months after therapy initiation. Therapy tolerability was assessed by the frequency and severity of local and/or systemic adverse events. Initially, the maximum urinary flow rate, residual urine volume, IPSS and prostate volume in patients from both groups did not differ statistically significantly. In the intergroup comparison, by 6 months of treatment (versus the treatment initiation), the average urinary flow rates in group 1 increased almost twice, and in group 2 only by 18% (p&lt;0.05). There was a decrease in the residual urine volume in patients of groups 1 and 2, respectively, by 52.6 and 22.6% (p&lt;0.05). The sum of the IPSS decreased by 46.1 and 21.5%, respectively (p&lt;0.05). At the same time, no significant tendency in the volume of the prostate gland in group 2 were revealed in the first 3 months of therapy, However, after 6 months there was an increase in the average prostate volume by 8.8%. In group 1, prostate volume decreased by almost 20% over 6 months of therapy. The tolerability of the studied drug was satisfactory; no adverse events were noted in any patient. Permixone is an effective drug with a high safety profile within the pathogenetic therapy of BPH, affecting a number of factors concerning the development and progression of this disease KEYWORDS: benign prostatic hyperplasia, lower urinary tract symptoms, microcirculation, Serenoa repens, phytotherapy, Laser Doppler flowmetry FOR CITATION: Nashivochnikova N.A. Informed method of choice concerning conservative therapy of BPH. Russian Medical Inquiry. 2022;6(4):187–194 (in Russ.). DOI: 10.32364/2587-6821-2022-6-4-187-194.

Medical therapy for asymptomatic men with benign prostatic hyperplasia: primum non nocere

Little is known about how benign prostatic hyperplasia (BPH) develops and why patients respond differently to medical therapy designed to reduce lower urinary tract symptoms (LUTS). The Medical Therapy of Prostatic Symptoms (MTOPS) trial randomized men with symptoms of BPH and followed response to medical therapy for up to 6 years. Treatment with a 5α-reductase inhibitor (5ARI) or an alpha-adrenergic receptor antagonist (α-blocker) reduced the risk of clinical progression, while men treated with combination therapy showed a 66% decrease in risk of progressive disease. However, medical therapies for BPH/LUTS are not effective in many patients. The reasons for nonresponse or loss of therapeutic response in the remaining patients over time are unknown. A better understanding of why patients fail to respond to medical therapy may have a major impact on developing new approaches for the medical treatment of BPH/LUTS. Prostaglandins (PG) act on G-protein-coupled receptors (GPCRs), where PGE2 and PGF2 elicit smooth muscle contraction. Therefore, we measured PG levels in the prostate tissue of BPH/LUTS patients to assess the possibility that this signaling pathway might explain the failure of medical therapy in BPH/LUTS patients. Surgical BPH (S-BPH) was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy and underwent surgical intervention to relieve LUTS. Control tissue was termed Incidental BPH (I-BPH). I-BPH was TZ obtained from men undergoing radical prostatectomy for low-volume, low-grade prostatic adenocarcinoma (PCa, Gleason score ≤ 7) confined to the peripheral zone. All TZ tissue was confirmed to be cancer-free. S-BPH patients divided into four subgroups: patients on α-blockers alone, 5ARI alone, combination therapy (α-blockers plus 5ARI), or no medical therapy (none) before surgical resection. I-BPH tissue was subgrouped by prior therapy (either on α-blockers or without prior medical therapy before prostatectomy). We measured prostatic tissue levels of prostaglandins (PGF2α , PGI2 , PGE2 , PGD2 , and TxA2 ), quantitative polymerase chain reaction levels of mRNAs encoding enzymes within the PG synthesis pathway, cellular distribution of COX1 (PTGS1) and COX2 (PTGS2), and tested the ability of PGs to contract bladder smooth muscle in an in vitro assay. All PGs were significantly elevated in TZ tissues from S-BPH patients (n = 36) compared to I-BPH patients (n = 15), regardless of the treatment subgroups. In S-BPH versus I-BPH, mRNA for PG synthetic enzymes COX1 and COX2 were significantly elevated. In addition, mRNA for enzymes that convert the precursor PGH2 to metabolite PGs were variable: PTGIS (which generates PGI2 ) and PTGDS (PGD2 ) were significantly elevated; nonsignificant increases were observed for PTGES (PGE2 ), AKR1C3 (PGF2α ), and TBxAS1 (TxA2 ). Within the I-BPH group, men responding to α-blockers for symptoms of BPH but requiring prostatectomy for PCa did not show elevated levels of COX1, COX2, or PGs. By immunohistochemistry, COX1 was predominantly observed in the prostatic stroma while COX2 was present in scattered luminal cells of isolated prostatic glands in S-BPH. PGE2 and PGF2α induced contraction of bladder smooth muscle in an in vitro assay. Furthermore, using the smooth muscle assay, we demonstrated that α-blockers that inhibit alpha-adrenergic receptors do not appear to inhibit PG stimulation of GPCRs in bladder muscle. Only patients who required surgery to relieve BPH/LUTS symptoms showed significantly increased tissue levels of PGs and the PG synthetic enzymes. Treatment of BPH/LUTS by inhibition of alpha-adrenergic receptors with pharmaceutical α-blockers or inhibiting androgenesis with 5ARI may fail because of elevated paracrine signaling by prostatic PGs that can cause smooth muscle contraction. In contrast to patients who fail medical therapy for BPH/LUTS, control I-BPH patients do not show the same evidence of elevated PG pathway signaling. Elevation of the PG pathway may explain, in part, why the risk of clinical progression in the MTOPS study was only reduced by 34% with α-blocker treatment.

• To examine how the introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) might have changed the indications, patient characteristics and outcomes in men undergoing transurethral resection of the prostate (TURP) over two decades (1988-2008). • All patients who underwent TURP for symptomatic BPH in a geographically defined area at our institution in 1988 (before the introduction of medical therapy for BPH), 1998 (when medical therapy was becoming an important therapy for BPH), and 2008 (when medical therapy was the primary first line therapy for BPH) were reviewed. • We assessed the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and pre- and postoperative events/complications. • There was a 60% decrease in TURPs from 1988 to 1998 with a moderate increase in number in 2008. • Failure of medical therapy was not an indication for TURP in 1988, but was at least one of the indications in 36% and 87% of patients in 1998 and 2008, respectively. • There was a substantial rise in the percentage of patients (but not total number or percentage of men at risk for BPH) presenting with acute or chronic urinary retention (AUR or CUR) at the time of their TURP (from 22.9% in 1988 to 42.9% in 2008, and from 14.6% in 1988 to 39.3% in 2008 for AUR and CUR, respectively). There was also a rise in the percentage of patients presenting with preoperative hydronephrosis (1.3% in 1988, 12.5% in 1998, 7.1% in 2008). • Inpatient stays decreased (from 4.1 day in 1988 to 2.7 days in 1998, and to 2.1 day in 2008), but the number of patients discharged with a catheter increased over the two decades (from 3.2% in 1988 to 12.5% in 1998, and to 28.6% in 2008). • The increasing use of medical therapy as a first line treatment for BPH has resulted in a dramatic decrease in TURPs which, in turn, has been associated with an apparent increase in risk of poor pre- and postoperative outcomes. However, the actual number (either the total number or as a percentage of men at risk for BPH) who have experienced these progression events has not changed and the postoperative outcomes are probably related to earlier catheter removal and hospital discharge. • It appears that we are performing TURP on the right patients.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are highly prevalent in the aging male. Similarly, the prevalence of metabolic syndrome is increasing worldwide, with mounting evidence that these two common conditions share more than age as a predisposing factor. The objective of this study was to determine if medical management of BPH is associated with an increased risk of new-onset diabetes mellitus (DM) in routine care. This population-based, retrospective cohort study expands on a parent study of linked administrative databases identifying patients diagnosed and treated for BPH between 2005 and 2015. The primary outcome of this secondary analysis was a new diagnosis of DM after the index date of BPH diagnosis. Covariates included age, dyslipidemia, hypertension, and vascular diseases. A Cox proportional hazards regression model was used for inferential statistical analysis. A total 129 223 men were identified with a BPH diagnosis and no prior history of DM. Of those men, 6390 (5%) were exposed to 5-alpha-reductase inhibitor (5-ARI), 39 592 (31%) exposed to alpha-blocker (AB), and 30 545 (24%) exposed to combination therapy. Compared to those men with no BPH medication use, those exposed to drugs had an increased risk of new DM. Men treated with combination therapy of 5-ARI and AB (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.25-1.35), 5-ARI monotherapy (HR 1.25, 95% CI 1.17-1.34), or AB monotherapy (HR 1.17, 95% CI 1.13-1.22) all were at higher risk of new DM diagnosis after adjusting for important covariates. When calculating the risk of a new diabetes diagnosis measured from the start of drug exposure, men treated with 5-ARIs had an increased risk of DM compared to AB monotherapy as the reference, with HR 1.12 (95% CI 1.03-1.21) for 5-ARI monotherapy and HR 1.20 (95% CI 1.14-1.25) for combination therapy. In this large, long-term, retrospective study of men with a BPH diagnosis in routine practice, the risk of a new diagnosis of DM was greater in patients receiving medical management compared to controls. This modest but significant increased risk was highest in men treated with any 5-ARIs, in combination as well as monotherapy, compared to the ABs.

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is one of the most common urinary disorders in elderly men. In recent years, pharmacotherapy of BPH has increased the efficacy, including combination treatment mostly with two drug classes, namely, 5-α-reductase inhibitors and α-1-adrenolytics (alpha blockers) with a different pharmacological activity. Although pharmacological treatment of BPH is a success story in urology, daily practice suggests that several medical needs remain unmet. We aimed to evaluate drug adherence in patients receiving pharmacological therapy to treat LUTS/BPH, and to analyze drug adherence among monotherapy and combination therapy. The sample population consisted of 758 men aged > 40 years who had been prescribed medications for LUTS/BPH during the index period between June 2015 and August 2016. Only alpha blockers and 5-α-reductase inhibitors (5ARIs) were considered in the analysis. Among ABs there were doxazosin, tamsulosin, alfuzosin, terazosin and among 5-α-reductase inhibitors it was only finasteride. Drug adherence was assessed in patients who were treated for a minimum of 6 months. Two levels of exposure were evaluated, follow-ups: ≥ 6 months, and ≥ 12 months. In patients who were treated for at least 6 months, the drug adherence rate was 32% and the 12-month drug adherence rate was 23%. We observed an inverse relationship between drug adherence rates and the duration of treatment - longer the duration of pharmacological therapy, lower was the drug adherence rate noted. Our study shows a low rate of overall drug adherence in patients diagnosed with BPH. It was observed that a low adherence rate is closely related to drug-related problems (DRP). Furthermore, this is a correlation between the degree of LUTS/BPH and adherence rate - the higher degree of LUTS/BPH, the higher adherence rate. Further studies are warranted focusing on assessing adherence to pharmacological therapy.

Personalized Medicine for the Management of Benign Prostatic Hyperplasia

Modifiable Risk Factors for Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: New Approaches to Old Problems