Medical Advancements in Benign Prostatic Hyperplasia Treatments.

PURPOSE OF REVIEW: This review aims to identify and summarize the current literature on the most recent therapeutic agents and combination strategies for the medical management of lower urinary tract symptoms resulting from benign prostatic hyperplasia. RECENT FINDINGS: The latest advancements in BPH therapy have been in combination strategies. Alpha blockers continue to be the mainstay of treatment, but research is exploring the synergistic benefits of combining them with 5-alpha reductase inhibitors (5-ARIs), phosphodiesterase-5 (PDE5) inhibitors, and beta-3 agonists. The alpha-blocker + 5-ARI combination remains ideal for enlarged, significantly reducing clinical progression risk compared to monotherapy. Alpha-blocker + PDE5 inhibitor combinations appear safe and potentially beneficial for men with concomitant erectile dysfunction; sildenafil might hold an edge over tadalafil based on limited data. Beta-3 agonists show synergistic effects with alpha blockers for residual storage symptoms, offering similar efficacy to anticholinergics but with a better side effect profile.

Medical management of benign prostatic hyperplasia.

Medical management of benign prostatic hyperplasia (BPH) has progressed gradually in recent years and remains the starting point for most symptomatic patients seeking treatment. Beyond well-known alpha-blockers and 5-alpha reductase inhibitors, there is growing evidence for the use of phosphodiesterase-5 inhibitors and beta-3 agonists in managing the condition, which may afford additional relief of "bothersome" symptoms in some patients. This review details contemporary medical management of BPH with an emphasis on the indications for certain classes of pharmacotherapy and their relative benefits and side effects. Surgical and procedural treatment of BPH is covered in a separate review.

Alpha-blockers: the magic pill for endourology-The great delusion.

PURPOSE: The present paper takes a different and more critical look at the role of alpha-blockers, sometimes nicknamed as "magical pills", in particular for stone disease and medical expulsive therapy (MET). METHODS: A non-systematic narrative review was performed, synthesizing pertinent information from selected articles, and critically evaluating their conclusions. Sometimes different views on alpha-blockers were laid bare, including curiosities or other entertaining nuances suitable to the present topic, but always maintaining sharp objectivity and the foremost scientific rigor. RESULTS AND CONCLUSIONS: Alpha-blockers seem to be a panacea, being used to treat a wide variety of non-urological diseases and conditions. Urological applications include erectile dysfunction to benign prostatic hyperplasia, from incontinence to urinary retention, or even to facilitate urinary stone passage along the urinary tract. Due to its versatility, alpha-blockers appear to be the Swiss army knife of urological medications. However, the efficacy of alpha-blockers for MET, pain management, or facilitating upper tract access is very disappointing, bringing no, or in some instances, only marginal benefits. Their treatment results are far from being significant or impressive let alone magical. Regular sexual intercourse is an effective alternative to alpha-blockers, providing faster ureteral stone expulsion rates and reducing the need for pain medication. Most of the research supporting alpha-blockers has been based on single-center, underpowered, low-quality studies. These low-quality studies biased several subsequent meta-analyses, contaminating them with their low-quality data, enhancing and prolonging this delusion. These results emphasize the need for large, multi-centric, unbiased, randomized, double-blinded, placebo-controlled trials to prevent future year-long delusions that may afflict any medical field.

Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

BACKGROUND: The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. METHOD: Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. RESULTS: Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. CONCLUSIONS: Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

[PHYTOTHERAPY AND NATURAL AGENTS IN SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA (BPH)].

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a very common condition among men over 50 years of age. Some patients require immediate surgical intervention for urinary retention. However, most men have a variety of symptoms that may require treatment. Medical therapy for BPH has been well known for many years including alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors. In recent years, men also receive anti-cholinergic agents, PDE5 inhibitors and other medical interventions. However, many men pursue alternative treatments and herbal medicines for BPH. We review herbs and herbal medicines that are used worldwide for symptomatic BPH. Many of them are supported by laboratory and clinical data. Mostly, mechanism of action are not fully understood but clinical benefit does support their use. Serenoa repens in hexanic extract (Permixon) is the only medicine that is backed with clinical data in high-quality clinical trials.

Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

PURPOSE: Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. METHODS: Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. RESULTS: A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. CONCLUSIONS: Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

A prospective, randomized, open-label, parallel trial comparing the efficacy of α-blocker or 5α-reductase inhibitor withdrawal to continued combination therapy on the maintenance of lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.

Clinical Effects of Oral Supplementation of Gamma-Cyclodextrin Curcumin Complex in Male Patients with Moderate-To-Severe Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. METHODS: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. RESULTS: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (-3.9, p < 0.001), IPSS-voiding (-2.0, p = 0.011), IPSS-total (-5.9, p < 0.001), IPSS-QoL (-3.9, p < 0.001), BII (-2.0, p < 0.001), Qmax (+3.1 mL/s, p < 0.001), Qmean (+1.9 mL/s, p = 0.005), post-void residual volume (-7.7 mL, p < 0.001), and PSA (-0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (-2.7, p < 0.001), IPSS-voiding (-1.3, p = 0.033), IPSS-total (-3.5, p < 0.001), IPSS-QoL (-1.1, p = 0.004), BII (-1.7, p = 0.006), Qmax (+1.0 mL/s, p = 0.006), and PSA (-0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (-1.3, p = 0.007), IPSS-total (-1.6, p = 0.034), IPSS-QoL (-1.1, p < 0.001), and BII (-2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. CONCLUSION: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

Effect of Terazosin Hydrochloride Combined with Interventional Embolisation on Prostate Volume and Quality of Life of Elderly Patients with Prostatic Hyperplasia.

OBJECTIVE: This study aimed to explore the effect of terazosin hydrochloride combined with interventional embolisation on prostate volume and quality of life (QOL) of elderly patients with prostatic hyperplasia (PH). METHODS: The clinical data of 175 elderly patients with PH admitted to Central Hospital Affiliated to Shandong First Medical University from July 2020 to July 2022 were selected for retrospective analysis. Based on different treatment regimens, 89 patients who received interventional embolisation alone were included in the control group (CG), and 86 patients undergoing interventional embolisation combined with terazosin hydrochloride were included in the study group (SG). The prostate volume, serum indicators, adverse reactions and QOL of the two groups before and after treatment were compared between the two groups. RESULTS: Before treatment, no significant difference in 36-item short-form health survey (SF-36) scores, serum tumour necrosis factor-α (TNF-α) and prostate-specific antigen (PSA) was observed in both groups (p > 0.05). After treatment, the SF-36 score in the SG was 78.20 ± 6.84 points, which was significantly higher than that in the CG (72.67 ± 5.94 points). In addition, the SG had remarkably lower residual urine volume and prostate volume, higher maximum flow rate and lower TNF-α and PSA levels compared with the CG (p < 0.05). The adverse reaction rate of the SG was only 4.65%, which was significantly lower than that of the CG (14.61%, p < 0.05). CONCLUSIONS: Terazosin hydrochloride combined with interventional embolisation overtly reduces the prostate volume and improves the clinical symptoms of patients with fewer side effects, which has a certain clinical application value.

Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients - a network meta-analysis.

BACKGROUND: Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, ß3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, ß3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients. METHODS: A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome. RESULTS: A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition. CONCLUSIONS: BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.

[Conservative and pharmacological treatment of benign prostatic hyperplasia : The German S2e-guideline 2023-part2]. / Konservative und medikamentöse Therapie des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 2.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH, in German guidelines: benign prostatic syndrome [BPS]) is considered the most common disease of the lower urinary tract in men and can have a tremendous impact on the quality-of-life of affected patients. Conservative and pharmacological therapy of this disease are of great importance, both in improving LUTS and reducing progression-related complications. OBJECTIVES: Presentation of the conservative and pharmacological treatment options according to the current German S2e guideline on BPS. MATERIALS AND METHODS: Summary and overview of chapters 9 and 10 of the current German S2e guideline on BPS. RESULTS: In addition to a controlled watchful waiting for BPS patients without an absolute indication for prostate surgery, a variety of phytopharmacological formulations and synthetic drugs according to the symptomatology and clinical progress are available. Phytotherapy should, due to inconsistent study data, only be considered for mild to moderate symptoms. Synthetic drugs include alpha-blockers, 5α-reductase inhibitors, phosphodiesterase inhibitors, antimuscarinics and, more recently, the ß3-agonist mirabegron in the current guideline. In addition, various combination therapies are listed and evaluated according to their indications, effects and side effects. CONCLUSIONS: The current German S2e guideline on the diagnosis and treatment of BPS provides an evidence-based foundation for finding the best possible and most effective medication.

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism.

Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective ß-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective ß-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.

Biopsychosocial approach to male chronic pelvic pain syndrome: recent treatments and trials.

INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic pain are often incomplete; appropriate management of CPPS includes recognition of biological, psychological, and social elements, known as the biopsychosocial model. OBJECTIVE: The aim of this narrative review is to investigate treatments for men with CPPS, with a special focus on those utilizing the biopsychosocial model of care. METHODS: A comprehensive literature search was conducted on the electronic databases PubMed, Embase, and Cochrane Library, using relevant Medical Subject Heading terms and keywords related to CPPS treatments. The search was limited to studies published in English from inception to January 2023. Additionally, reference lists of selected studies were manually reviewed to find studies not identified by the initial search. Studies were included if they investigated pharmacologic or nonpharmacologic treatments for men with CPPS. RESULTS: A total of 30 studies met the inclusion criteria. Antibiotics, α-blockers, nonsteroidal anti-inflammatory drugs, gabapentinoids, antidepressants, and phosphodiesterase type 5 inhibitors were among the pharmacologic agents included in trials attempting to reduce symptoms of male CPPS. Studies that focused on treating CPPS without medication included interventions such as shockwave therapy, acupuncture, physical therapy, botulinum toxin, cryotherapy, electrotherapy, exercise, and cognitive behavioral therapy. CONCLUSION: α-Blockers and nonsteroidal anti-inflammatory drugs have shown promising results in treating CPPS in men, while the effectiveness of antibiotics remains controversial. Antidepressants and phosphodiesterase type 5 inhibitors may also be useful in decreasing symptoms in patients with CPPS. Treatments such as pelvic floor muscle therapy, acupuncture, shockwave therapy, and cognitive behavioral therapy must be considered effective complements to medical management in men with CPPS. While these interventions demonstrate benefits as monotherapies, the individualization and combination of treatment modalities are likely to result in reduced pain and improved quality of life.

Centrally acting antihypertensives and alpha-blockers in people at risk of falls: therapeutic dilemmas-a clinical review.

PURPOSE: The aim of this clinical review was to summarise the existing knowledge on the adverse effects of alpha-blockers and centrally acting antihypertensives, the effect these may have on falls risk, and guide deprescribing of these medications. METHODS: Literature searches were conducted using PubMed and Embase. Additional articles were identified by searching reference lists and reference to personal libraries. We discuss the place of alpha-blockers and centrally acting antihypertensives in the treatment of hypertension and methods for deprescribing. RESULTS: Alpha-blockers and centrally acting antihypertensives are no longer recommended for the treatment of hypertension unless all other agents are contraindicated or not tolerated. These medications carry a significant falls risk and non-falls risk-associated side effects. Tools to aid and guide de-prescribing and monitoring of the withdrawal of these medication classes are available to assist the clinician including information on reducing the risk of withdrawal syndromes. CONCLUSIONS: Centrally acting antihypertensives and alpha-blockers increase the risk of falls through a variety of mechanisms-principally by increasing the risk of hypotension, orthostatic hypotension, arrhythmias and sedation. These agents should be prioritised for de-prescribing in older frailer individuals. We identify a number of tools and a withdrawal protocol to aid the clinician in identifying and de-prescribing these medications.

[The results of the multicenter prospective comparative study of Androgel in men with endogenous testosterone deficiency and lower urinary tract symptoms, associated with benign prostate hyperplasia (POTOK)].

AIM: To evaluate the efficacy and safety of using Androgel in men with endogenous testosterone deficiency and lower urinary tract symptoms (LUTS), associated with benign prostatic hyperplasia (BPH) in routine clinical practice. MATERIALS AND METHODS: The multicenter, prospective, comparative study "POTOK" included 500 patients aged over 50 years with biochemical signs of testosterone deficiency (morning total testosterone concentration <12.1 nmol/l) and LUTS/BPH (International Prostatic Symptoms Score [IPSS] score of 8-19). The recruitment and monitoring of patients was carried out in 2022 in 40 clinics in Russia. Depending on the therapy, all patients were divided into two groups. The physician's decision to prescribe a specific drug (according to the approved patient information leaflet), as well as the subsequent follow-up scheme and therapy, was made a priori and independently of patient. In the first group (n=250) alpha-blockers and Androgel were prescribed, while in the second group (n=250) patients received monotherapy with alpha-blockers. The follow-up duration was 6 months. The efficiency of the therapy was evaluated after 3 and 6 months according to IPSS, symptoms of androgen deficiency (AMS and IIEF scores), uroflowmetry (peak flow rate, total urination volume), ultrasound study (postvoid residual and prostate volume). Safety was assessed by the total number of adverse events, stratified by severity and frequency. Statistical analysis was carried out using IBM SPSS 26.0. RESULTS: According to the primary end-point (IPSS score), there were significant differences between groups 1 and 2 after 3 months (11 vs. 12 points, p=0.009) and 6 months of therapy (9 vs. 11 points, p<0.001). There were also significant differences in the severity of symptoms of androgen deficiency after 3 and 6 months of therapy according to AMS score of 35 vs. 38 points (p<0.001) and 28 vs. 36 points (p<0.001), respectively. According to IIEF, all domains (erectile and orgasmic functions, libido, sexual satisfaction with and general satisfaction) were better in group 1 (p<0.001). After 6 months, uroflowmetry values also differed. In group 1 Qmax was 16 ml/s compared to 15.2 ml/s in group 2 (p=0.004); postvoid residual was 10 ml vs. 15.5 ml, respectively (p=0.001). The prostate volume in group 1 after 6 months of treatment was significantly lower (39.5 cc) compared with group 2 (43.3 cc; p=0.002). During the study, 18 mild AEs, 2 moderate AEs, and 1 severe AE were identified without significant differences between the groups (p>0.05). CONCLUSION: The results of study "POTOK" showed greater efficacy and comparable safety of alpha-blockers in combination with Androgel compared with monotherapy with alpha-blockers in men with LUTS/BPH and endogenous testosterone deficiency in routine clinical practice. The increase in serum testosterone concentrations to normal values in patients with age-related hypogonadism favorably influence on the severity of LUTS and the potentiate the effect of the standard monotherapy with alpha-blockers.

Ureteral Stent-Related Symptoms and Pharmacotherapy: A Brief Narrative Review.

The purpose of this article is to review the effects of different types of pharmacotherapy on symptoms that affect the quality of a patient's life after stent insertion. A thorough Medline/PubMed nonsystematic review was conducted from 1987 to January 2023, using the terms: "pigtail" OR "ureteral stents" AND "lower urinary tracts symptoms" OR "LUTS" AND "pharmacotherapy" OR "drugs". Relevant studies conducted in humans and reported in English language were included. The available reviews and articles associating the use of drugs with stent-related symptoms (SRS) provide conflicting results. Most of them show a clear benefit of alpha blockers, particularly alfuzosin, on treating urinary SRS, and hence there is a strong recommendation for the use of alpha blockers for the treatment of SRS in the guidelines of the European Association of Urology. Anticholinergics and mirabegron have shown a significant benefit in dealing with irritative bladder symptoms. In contrast, the findings for combination therapies are contradictory, with some studies showing that combination therapy is no superior to monotherapy with regards to most of the subsets of the Ureteral Stent Symptom Questionnaire (USSQ), whereas others present a clear benefit of combination therapies, specifically silodosin and solifenacin, in treating stent-associated lower urinary tract symptoms (LUTS), in comparison with any other type of monotherapy or combination therapy. Many studies suggest that some categories of pharmacotherapy, such as alpha blockers, can alleviate SRS. However, there is conflicting evidence concerning most other types of medical treatment. Randomized trials with the largest number of patients are needed to investigate the effectiveness of novel approaches on SRS.

Clinical and Urodynamic Predictors for Failure of Medical Management with Alpha Blockers in PBNO: A Retrospective Cohort Analysis.

OBJECTIVE: To evaluate the clinical and urodynamic variables that may predict the failure of alpha-blockers in primary bladder neck obstruction (PBNO) patients. Alpha-blockers are useful as a treatment option in patients with PBNO. Nonresponders need to undergo bladder neck incision (BNI). Little is known about the predictive factors determining the success of treatment. MATERIALS AND METHODS: This was a retrospective study, spanning over a period of 8 years. PBNO was diagnosed in the presence of a bladder outlet obstruction index (BOOI) >40 with video-urodynamic evidence of obstruction at the bladder neck. The patients were initially managed with alpha-blockers (alfuzosin and tamsulosin) for 3-6 months, and BNI contemplated when pharmacotherapy failed. The patients with upper tract changes managed with upfront BNI or clean intermittent catheterization were excluded. The data for the international prostate symptom score (IPSS), uroflowmetry, urodynamic studies, and ultrasonography of pre and post-treatment periods were reviewed. Treatment outcomes were defined as complete response (>50% improvement in Qmax and IPSS score) and partial response (30%-50% improvement in Qmax and IPSS score) at 3 or 6 months. RESULTS: Ninety-nine patients were analyzed. 21 patients underwent BNI for the failure of medical management and 31 for recurrence of symptoms at a mean follow-up of 18.8 ± 3.5 months (12-70 months). Independent predictors of failure of pharmacotherapy with alpha-blockers were age (P = .021), Pdet@Qmax (P = .015), and BOOI (P = .019). CONCLUSION: Alpha-blockers are more likely to fail in PBNO in younger patients generating higher voiding pressures and BOOI > 60.

Abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability.

Background: There is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability. Methods: 83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression. Results: The results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m2, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability. Conclusion: The purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.

[Drugs for Neurogenic Bladder Dysfunction].

Urinary dysfunction includes an overactive bladder (OAB), post-void residual (PVR)/retention, or both entities. Brain diseases cause OAB, peripheral neuropathies are associated with significant PVR/retention, and multisystem atrophy/spinal cord diseases result in a combination of OAB and PVR/retention. Selective beta 3 adrenergic receptor agonists or anticholinergic agents are the first-choice treatment for OAB and clean intermittent self-catheterization, alpha-blocker and cholinergic stimulant therapy for significant PVR/retention. These therapies may be useful to maximize patients' quality of life and prevent serious complications, such as urosepsis or kidney dysfunction.

How Would You Manage This Patient With Benign Prostatic Hyperplasia? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) are common in older patients assigned male sex at birth, regardless of gender identity, and treatment of these symptoms is therefore common in primary care practice. In 2021, the American Urological Association published guidelines for management of BPH. They recommend using a standardized scoring system such as the International Prostate Symptom Score to help establish a diagnosis and to monitor the efficacy of interventions, α-blockers as the first-choice pharmacotherapy option, and 5α-reductase inhibitors for patients with prostate size estimated to be at least 30 cc. Tadalafil is another option regardless of erectile dysfunction. Combination therapies with α-blockers and 5α-reductase inhibitors, anticholinergic agents, or ß3-agonists are effective options. A surgical referral is warranted if the BPH results in chronic kidney disease, refractory urinary retention, or recurrent urinary tract infections; if there is concern for bladder or prostate cancer; or if symptoms do not respond to medical therapy. In this article, a general internal medicine physician and a urologist discuss the treatment options and how they would apply their recommendations to a patient who wishes to learn more about his options.