Overview of current pharmacotherapeutic options in benign prostatic hyperplasia

INTRODUCTION Benign prostatic hyperplasia (BPH) represents the histological entity of prostate cell proliferation, which inflicts a gradually increasing obstruction of the bladder outlet and is accompanied by a progressing manifestation of lower urinary tract symptoms (LUTS). BPH management algorithm includes conservative measures, pharmaceutical agents, and surgical procedures. AREAS COVERED A comprehensive literature review was performed using PubMed, Scopus, and Google Scholar databases to identify publications written in English, analyzing BPH pharmaceutical treatment. The search was conducted from January 2000 to January 2023. Six main drug classes can be administered, either as monotherapy or in combination. Furthermore, the authors provide current direction of research on future medications, which focuses on a more etiological interference to the BPH pathophysiological mechanism. EXPERT OPINION The available medications represent an effective first-line step of BPH/LUTS therapy. Currently, the administration of BPH medications is tailored to patient/disease characteristics and entails long-time adherence to therapy. The emergence of new surgical modalities, which combine significantly lower morbidity compared to standard procedures and more durable effects than the available medications, seems to challenge the current treatment algorithm. More direct comparisons and the increasing experience with these surgical modalities will delineate the switch points between various therapy levels along the BPH management sequence.

[1]  B. Sander,et al.  Cost-utility of minimally invasive therapies vs. pharmacotherapy as initial therapy for benign prostatic hyperplasia: A Canadian healthcare payer perspective. , 2022, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[2]  H. Woo,et al.  Benign prostatic hyperplasia , 2022, Nature Reviews Disease Primers.

[3]  C. Stief,et al.  Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells. , 2022, Life sciences.

[4]  D. Hennessey,et al.  Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis. , 2022, Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica.

[5]  C. Stief,et al.  Inhibition of Human Prostate and Bladder Smooth Muscle Contraction, Vasoconstriction of Porcine Renal and Coronary Arteries, and Growth-Related Functions of Prostate Stromal Cells by Presumed Small Molecule Gαq/11 Inhibitor, YM-254890 , 2022, Frontiers in Physiology.

[6]  Ruonan Sun,et al.  Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging , 2022, Frontiers in Immunology.

[7]  Jiansong Wang,et al.  Comparative Efficacy of Different Drugs for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Bayesian Network Meta-Analysis , 2022, Frontiers in Pharmacology.

[8]  X. Qin,et al.  The efficacy and safety of dutasteride and finasteride in patients with benign prostatic hyperplasia: a systematic review and meta-analysis , 2022, Translational andrology and urology.

[9]  C. Stief,et al.  Inhibition of Full Smooth Muscle Contraction in Isolated Human Detrusor Tissues by Mirabegron Is Limited to Off-Target Inhibition of Neurogenic Contractions , 2022, The Journal of Pharmacology and Experimental Therapeutics.

[10]  C. Stief,et al.  Lenalidomide and pomalidomide inhibit growth of prostate stromal cells and human prostate smooth muscle contraction. , 2021, Life sciences.

[11]  C. Stief,et al.  Concentration-dependent alpha1-Adrenoceptor Antagonism and Inhibition of Neurogenic Smooth Muscle Contraction by Mirabegron in the Human Prostate , 2021, Frontiers in Pharmacology.

[12]  J. Corcos,et al.  Is Early Surgical Treatment for Benign Prostatic Hyperplasia Preferable to Prolonged Medical Therapy: Pros and Cons , 2021, Medicina.

[13]  K. Ohba,et al.  Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia , 2021, Molecules.

[14]  C. Welliver,et al.  National Trends in the Management of Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia , 2020, Current Urology Reports.

[15]  M. Ansari,et al.  The effect of vitamin D supplementation on the progression of benign prostatic hyperplasia: A randomized controlled trial. , 2020, Clinical nutrition.

[16]  R. Platt,et al.  Trends in the pharmacological treatment of benign prostatic hyperplasia in the UK from 1998 to 2016: a population-based cohort study , 2020, World Journal of Urology.

[17]  N. Maitland,et al.  Benign prostatic hyperplasia – what do we know? , 2020, BJU international.

[18]  M. Radwan,et al.  Efficacy and safety of mirabegron versus solifenacin as additional therapy for persistent OAB symptoms after tamsulosin monotherapy in men with probable BPO , 2020, World Journal of Urology.

[19]  K. Shyamprasad,et al.  A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency , 2020, BMC Urology.

[20]  S. Kaplan,et al.  An evaluation of the federal adverse events reporting system data on adverse effects of 5-alpha reductase inhibitors , 2020, World Journal of Urology.

[21]  J. Yaxley,et al.  Management of benign prostatic hyperplasia in the 21st century: temporal trends in Australian population‐based data , 2020, BJU international.

[22]  A. Salonia,et al.  Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia , 2020, World Journal of Urology.

[23]  A. Traish Post-finasteride syndrome: a surmountable challenge for clinicians. , 2020, Fertility and sterility.

[24]  C. Schermer,et al.  Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR). , 2019, European urology.

[25]  H. Kakizaki,et al.  Mirabegron Add-on Therapy to Tamsulosin for the Treatment of Overactive Bladder in Men with Lower Urinary Tract Symptoms: A Randomized, Placebo-controlled Study (MATCH). , 2019, European urology focus.

[26]  H. Woo,et al.  Clinical Trials in Benign Prostatic Hyperplasia: A Moving Target of Success. , 2019, European urology focus.

[27]  G. Russo,et al.  Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer. , 2019, Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica.

[28]  D. Tsikas,et al.  Emerging drugs to target lower urinary tract symptomatology (LUTS)/benign prostatic hyperplasia (BPH): focus on the prostate , 2019, World Journal of Urology.

[29]  J. Hippisley-Cox,et al.  Anticholinergic Drug Exposure and the Risk of Dementia , 2019, JAMA internal medicine.

[30]  N. Farber,et al.  Comparing Outcomes of Medical Management and Minimally Invasive Surgical Techniques for Lower Urinary Tract Symptoms due to BPH , 2019, Current Urology Reports.

[31]  G. Burgio,et al.  Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction , 2019, The aging male : the official journal of the International Society for the Study of the Aging Male.

[32]  W. White,et al.  Cardiovascular safety of mirabegron: analysis of an integrated clinical trial database of patients with overactive bladder syndrome. , 2018, Journal of the American Society of Hypertension : JASH.

[33]  K. McVary,et al.  A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome. , 2018, Urology.

[34]  C. Kelleher,et al.  Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis. , 2018, European urology.

[35]  S. de Wachter,et al.  Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe , 2018, Neurourology and urodynamics.

[36]  H. Kuo,et al.  Safety and therapeutic efficacy of mirabegron 25 mg in older patients with overactive bladder and multiple comorbidities , 2018, Geriatrics & gerontology international.

[37]  M. Herdman,et al.  Efficacy and safety of a hexanic extract of Serenoa repens (Permixon®) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta‐analysis of randomised controlled trials and observational studies , 2018, BJU international.

[38]  Yuanshan Cui,et al.  Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile Dysfunction: A Systematic Review and Meta‐analysis , 2018, Lower urinary tract symptoms.

[39]  F. Montorsi,et al.  Clinically Meaningful Improvements in LUTS/BPH Severity in Men Treated with Silodosin Plus Hexanic Extract of Serenoa Repens or Silodosin Alone , 2017, Scientific Reports.

[40]  C. Chapple,et al.  Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice. , 2017, European urology.

[41]  T. Matsuda,et al.  Comparison of Silodosin Monotherapy vs Silodosin With Tadalafil Add-on Therapy in Patients With Benign Prostatic Hyperplasia. , 2017, Urology.

[42]  Kwangsung Park,et al.  Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. , 2017, The journal of sexual medicine.

[43]  M. Oelke,et al.  Efficacy and safety of daily mirabegron 50 mg in male patients with overactive bladder: a critical analysis of five phase III studies , 2017, Therapeutic advances in urology.

[44]  D. Juurlink,et al.  The Cardiovascular Safety of Dutasteride , 2017, The Journal of urology.

[45]  T. Wilt,et al.  Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis. , 2017, European urology.

[46]  S. Vouri,et al.  Adverse events and treatment discontinuations of antimuscarinics for the treatment of overactive bladder in older adults: A systematic review and meta-analysis. , 2017, Archives of gerontology and geriatrics.

[47]  F. Montorsi,et al.  Efficacy and Safety of Hexanic Lipidosterolic Extract of Serenoa repens (Permixon) in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Systematic Review and Meta-analysis of Randomized Controlled Trials. , 2016, European urology focus.

[48]  A. Tubaro,et al.  Inflammatory mediators in the development and progression of benign prostatic hyperplasia , 2016, Nature Reviews Urology.

[49]  L. Cardozo,et al.  Current and future pharmacotherapy for treating overactive bladder , 2016, Expert opinion on pharmacotherapy.

[50]  N. Longo,et al.  α1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Urodynamic Studies. , 2016, European urology.

[51]  E. Antunes,et al.  Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3‐adrenoceptor activation and α1‐adrenoceptor blockade , 2016, British journal of pharmacology.

[52]  E. McArthur,et al.  The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study , 2015, BMJ : British Medical Journal.

[53]  A. Sahai,et al.  PDE-5 Inhibitors for BPH-Associated LUTS. , 2015, Current drug targets.

[54]  L. Cindolo,et al.  Patient’s adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy? , 2015, BMC Urology.

[55]  T. Uchiyama,et al.  The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia. , 2015, Journal of pharmacological sciences.

[56]  C. Roehrborn,et al.  Treatment satisfaction and clinically meaningful symptom improvement in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: Secondary results from a 6‐month, randomized, double‐blind study comparing finasteride plus tadalafil with finasteride pl , 2015, International journal of urology : official journal of the Japanese Urological Association.

[57]  O. Yamaguchi,et al.  Efficacy and Safety of the Selective β3‐Adrenoceptor Agonist Mirabegron in Japanese Patients with Overactive Bladder: A Randomized, Double‐Blind, Placebo‐Controlled, Dose‐Finding Study , 2015, Lower urinary tract symptoms.

[58]  C. De Monte,et al.  Modern extraction techniques and their impact on the pharmacological profile of Serenoa repens extracts for the treatment of lower urinary tract symptoms , 2014, BMC Urology.

[59]  M. Carini,et al.  Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. , 2014, The journal of sexual medicine.

[60]  V. Nitti,et al.  Urodynamics and safety of the β₃-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. , 2013, The Journal of urology.

[61]  M. Carini,et al.  PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS , 2013, The Prostate.

[62]  D. Cox,et al.  Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies. , 2013, Urology.

[63]  C. Liao,et al.  Predictors of successful first-line antimuscarinic monotherapy in men with enlarged prostate and predominant storage symptoms. , 2013, Urology.

[64]  M. Carini,et al.  PDE5-Is for the Treatment of Concomitant ED and LUTS/BPH , 2013, Current Bladder Dysfunction Reports.

[65]  M. Elhilali,et al.  Finasteride monotherapy maintains stable lower urinary tract symptoms in men with benign prostatic hyperplasia following cessation of alpha blockers. , 2013, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[66]  L. Birder,et al.  The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. , 2013, European urology.

[67]  M. Carini,et al.  A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. , 2012, The journal of sexual medicine.

[68]  C. Stief,et al.  The role of antimuscarinics in the management of men with symptoms of overactive bladder associated with concomitant bladder outlet obstruction: an update. , 2011, European urology.

[69]  I. Chatziralli,et al.  Risk factors for intraoperative floppy iris syndrome: a meta-analysis. , 2011, Ophthalmology.

[70]  K. Andersson Antimuscarinic mechanisms and the overactive detrusor: an update. , 2011, European urology.

[71]  T. Tammela,et al.  Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. , 2011, European urology.

[72]  C. Roehrborn,et al.  Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. , 2010, The Journal of urology.

[73]  J. Imperato-McGinley,et al.  5α‐Reductase Isozymes and Androgen Actions in the Prostate , 2009, Annals of the New York Academy of Sciences.

[74]  J. Nickel,et al.  A meta-analysis of the vascular-related safety profile and efficacy of α-adrenergic blockers for symptoms related to benign prostatic hyperplasia , 2008, International journal of clinical practice.

[75]  C. Stief,et al.  A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. , 2008, European urology.

[76]  P. Abrams,et al.  Do α1‐adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance? , 2008, Neurourology and urodynamics.

[77]  K. McVary,et al.  Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. , 2007, The Journal of urology.

[78]  M. Chancellor,et al.  The promise of beta3-adrenoceptor agonists to treat the overactive bladder. , 2006, The Urologic clinics of North America.

[79]  M. Michel,et al.  α1‐, α2‐ and β‐adrenoceptors in the urinary bladder, urethra and prostate , 2006 .

[80]  M. Marberger,et al.  Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years. , 2004, Urology.

[81]  G. Cunningham,et al.  Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. , 2004, The Journal of clinical endocrinology and metabolism.

[82]  M. Takeuchi,et al.  M3 receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland , 2002, Naunyn-Schmiedeberg's Archives of Pharmacology.

[83]  R. Rittmaster,et al.  Evidence for atrophy and apoptosis in the prostates of men given finasteride. , 1996, The Journal of clinical endocrinology and metabolism.

[84]  C. Stief,et al.  Non‐Adrenergic, Tamsulosin‐Insensitive Smooth Muscle Contraction is Sufficient to Replace α1‐Adrenergic Tension in the Human Prostate , 2017, The Prostate.

[85]  A. Rojas,et al.  Tolterodine and Tamsulosin for Treatment of Men With Lower Urinary Tract Symptoms and Overactive Bladder , 2011 .

[86]  M. Chancellor,et al.  Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways. , 2005, Urology.

[87]  M. Wyllie,et al.  Not all brands are created equal: a comparison of selected components of different brands of Serenoa repens extract , 2004, Prostate Cancer and Prostatic Diseases.