madman
Super Moderator
Abstract
Introduction
Benign prostatic hyperplasia (BPH) is condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH.
Areas covered
We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH.
Expert opinion
BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.
1. Background
Benign prostatic hyperplasia (BPH) stands as a prevalent condition primarily affecting aging males, necessitating a clear definition before delving into its medical therapies [1]. As men approach their fifties, more than half of them will develop BPH, and a significant portion of these individuals will experience lower urinary tract symptoms (LUTS) attributed to BPH [2–4]. LUTS can significantly impede one's storage (incontinence, nocturia, frequency) and voiding (retention, weak stream) ability, resulting in a diminished quality of life (QoL) [5]. The aging population has led and will continue to lead to a steady increase in the prevalence and incidence of LUTS secondary to BPH [6].
A multicenter observational study involving over 800 males aged 50–80 years evaluated lifestyle factors, prostate-related variables, and symptom severity [7]. The study revealed a strong association between the severity of symptoms, as assessed by the AUA-SS (American Urological Association Symptom Score), and decreased QoL. Furthermore, the impact of BPH extends beyond the patient; surveys of couples in which the male partner had BPH demonstrated that the female partners experienced various morbidities, including sleep disturbance, disruption to social life, and increased psychological burden, with the severity of the patient's symptoms correlating with the degree of morbidity in the partner [8,9]. Given the significant burden posed by BPH, this review aims to scrutinize existing medical therapies for LUTS/BPH and explore emerging drugs currently under investigation
2. Medical Need
Assessing a patient with LUTS secondary to BPH requires a comprehensive evaluation that considers various factors. The initial assessment encompasses a thorough history and physical examination, taking into account the patient's age, comorbidities, risk of disease progression,available treatment options, QoL, and sexual activity.
4. Existing treatments
4.1. Alpha blockers
4.2. 5-ARI reductase inhibitors
4.3. PDE5 inhibitors
4.4. Anticholinergics
4.5. β-3 agonist
5. Combination therapy
5.1. Alpha blocker with 5ARIs
5.2. Alpha blockers and PDE5 inhibitors
5.3. Alpha blockers with anticholinergics
5.4. Alpha blockers and beta-3 agonists
5.5. Antimuscarinics and 5 ARIs
5.6 Antimuscarinic plus beta-3 agonists
5.7. 5 ARIs and PDE5 inhibitors
6. Market Review
7. Current Research Goals
8. Scientific Rationale and Risk Factors
9. Competitive environment
10. Novel pharmacotherapies
10.1. Luteinizing hormone-releasing hormone (LHRH) antagonists
10.2. Nonsteroidal anti-inflammatory drugs (NSAIDs)
10.3. NX-1207
10.4. PRX302 (Topsalysin)
10.5. Afala
10.6. GV1001 (Tertomotide)
10.7. Angiotensin converting enzyme inhibitors
10.8. Progestogens
10.9. Onabotulinumtoxin A
11 Phytotherapy and Supplements
11.1 Serenoa Repens
11.2. Equol
11.3. Pomegranate
11.4 Carotenoids
11.5. Vitamin D3 (calcitriol) analogs
9. Potential Development Issues
10. Conclusion
BPH is a complex condition that extends beyond just prostatic disease. It involves various pathophysiological factors in the lower urinary tract. There is a wide array of medical treatments available, and healthcare professionals must carefully select the most suitable drug or drugs for individual patients. With the aging population, the number of symptomatic patients seeking relief is on the rise. As of now, alpha-blockers and 5ARIs are the most commonly prescribed medical treatments due to their tolerability, despite potential side effects. PDE5 inhibitors are also gaining traction in patients who struggle with said side effects. New treatment options have shown promise in clinical trials, offering relief to patients. However, these treatments often lack the durability, cost-effectiveness, and side-effect profiles of traditional medications.
Future research in basic science is crucial to gain a deeper understanding of existing treatment options and expand the pharmacological arsenal for men with LUTS secondary to BPH. This comprehensive strategy aims to enhance IPSS and Qmax while minimizing adverse effects. Developing therapies with improved long-term efficacy, reduced side effects, and affordability is essential to meet the evolving healthcare needs of aging populations. By addressing these challenges, we can provide better care and improved quality of life for individuals with LUTS and BPH.
11. Expert opinion
The landscape of BPH treatment is on the verge of significant transformation, with several novel drugs currently in clinical trials that hold the potential to become viable treatment options. While some of these innovative therapies are exploring established therapeutic pathways, others are venturing into new and uncharted territory. It is imperative that these emerging frontiers are thoroughly studied to deepen our understanding of BPH's etiology and potentially reshape the course of its progression.
One crucial aspect of this evolving field is the emphasis on basic science research. Investing in fundamental research is essential for unraveling the intricate pathogenesis of BPH. By delving into the underlying molecular and cellular mechanisms, we can gain invaluable insights that may lead to the development of more targeted and effective medications. BPH is not a one-size-fits all condition; it involves a complex interplay of various factors, necessitating drugs that can target these diverse components.
Another aspect of BPH treatment that continues to gain popularity is using a multi-drug regimen. As the number of treatments increases, and as those treatments become more mechanistically specific with smaller side effect profiles, the appeal of using multiple medications with complimentary effects will only increase. This will allow physicians to carefully tailor medications to maximize patient quality of life.
However, despite the promising potential of these new treatments, there are challenges that need to be addressed. Many therapies that have demonstrated efficacy in laboratory settings have struggled to replicate the same success in clinical trials. This disconnect can be attributed to various factors, including financial constraints, practicality issues, and unforeseen complications. For instance, the use of rho-kinase inhibitors, which have shown promise in vitro, faces practical hurdles in translating their benefits to clinical settings [125].
Over the next several years, we anticipate the emergence of new drugs that could offer durable and effective treatment options for BPH. To realize this potential, it is crucial for all stakeholders involved in the process to collaborate seamlessly. This collective effort should involve researchers dedicated to exploring new avenues of treatment, pharmaceutical companies committed to developing these therapies, government bodies providing support and regulation, and physicians at the forefront of patient care.
Introduction
Benign prostatic hyperplasia (BPH) is condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH.
Areas covered
We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH.
Expert opinion
BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.
1. Background
Benign prostatic hyperplasia (BPH) stands as a prevalent condition primarily affecting aging males, necessitating a clear definition before delving into its medical therapies [1]. As men approach their fifties, more than half of them will develop BPH, and a significant portion of these individuals will experience lower urinary tract symptoms (LUTS) attributed to BPH [2–4]. LUTS can significantly impede one's storage (incontinence, nocturia, frequency) and voiding (retention, weak stream) ability, resulting in a diminished quality of life (QoL) [5]. The aging population has led and will continue to lead to a steady increase in the prevalence and incidence of LUTS secondary to BPH [6].
A multicenter observational study involving over 800 males aged 50–80 years evaluated lifestyle factors, prostate-related variables, and symptom severity [7]. The study revealed a strong association between the severity of symptoms, as assessed by the AUA-SS (American Urological Association Symptom Score), and decreased QoL. Furthermore, the impact of BPH extends beyond the patient; surveys of couples in which the male partner had BPH demonstrated that the female partners experienced various morbidities, including sleep disturbance, disruption to social life, and increased psychological burden, with the severity of the patient's symptoms correlating with the degree of morbidity in the partner [8,9]. Given the significant burden posed by BPH, this review aims to scrutinize existing medical therapies for LUTS/BPH and explore emerging drugs currently under investigation
2. Medical Need
Assessing a patient with LUTS secondary to BPH requires a comprehensive evaluation that considers various factors. The initial assessment encompasses a thorough history and physical examination, taking into account the patient's age, comorbidities, risk of disease progression,available treatment options, QoL, and sexual activity.
4. Existing treatments
4.1. Alpha blockers
4.2. 5-ARI reductase inhibitors
4.3. PDE5 inhibitors
4.4. Anticholinergics
4.5. β-3 agonist
5. Combination therapy
5.1. Alpha blocker with 5ARIs
5.2. Alpha blockers and PDE5 inhibitors
5.3. Alpha blockers with anticholinergics
5.4. Alpha blockers and beta-3 agonists
5.5. Antimuscarinics and 5 ARIs
5.6 Antimuscarinic plus beta-3 agonists
5.7. 5 ARIs and PDE5 inhibitors
6. Market Review
7. Current Research Goals
8. Scientific Rationale and Risk Factors
9. Competitive environment
10. Novel pharmacotherapies
10.1. Luteinizing hormone-releasing hormone (LHRH) antagonists
10.2. Nonsteroidal anti-inflammatory drugs (NSAIDs)
10.3. NX-1207
10.4. PRX302 (Topsalysin)
10.5. Afala
10.6. GV1001 (Tertomotide)
10.7. Angiotensin converting enzyme inhibitors
10.8. Progestogens
10.9. Onabotulinumtoxin A
11 Phytotherapy and Supplements
11.1 Serenoa Repens
11.2. Equol
11.3. Pomegranate
11.4 Carotenoids
11.5. Vitamin D3 (calcitriol) analogs
9. Potential Development Issues
10. Conclusion
BPH is a complex condition that extends beyond just prostatic disease. It involves various pathophysiological factors in the lower urinary tract. There is a wide array of medical treatments available, and healthcare professionals must carefully select the most suitable drug or drugs for individual patients. With the aging population, the number of symptomatic patients seeking relief is on the rise. As of now, alpha-blockers and 5ARIs are the most commonly prescribed medical treatments due to their tolerability, despite potential side effects. PDE5 inhibitors are also gaining traction in patients who struggle with said side effects. New treatment options have shown promise in clinical trials, offering relief to patients. However, these treatments often lack the durability, cost-effectiveness, and side-effect profiles of traditional medications.
Future research in basic science is crucial to gain a deeper understanding of existing treatment options and expand the pharmacological arsenal for men with LUTS secondary to BPH. This comprehensive strategy aims to enhance IPSS and Qmax while minimizing adverse effects. Developing therapies with improved long-term efficacy, reduced side effects, and affordability is essential to meet the evolving healthcare needs of aging populations. By addressing these challenges, we can provide better care and improved quality of life for individuals with LUTS and BPH.
11. Expert opinion
The landscape of BPH treatment is on the verge of significant transformation, with several novel drugs currently in clinical trials that hold the potential to become viable treatment options. While some of these innovative therapies are exploring established therapeutic pathways, others are venturing into new and uncharted territory. It is imperative that these emerging frontiers are thoroughly studied to deepen our understanding of BPH's etiology and potentially reshape the course of its progression.
One crucial aspect of this evolving field is the emphasis on basic science research. Investing in fundamental research is essential for unraveling the intricate pathogenesis of BPH. By delving into the underlying molecular and cellular mechanisms, we can gain invaluable insights that may lead to the development of more targeted and effective medications. BPH is not a one-size-fits all condition; it involves a complex interplay of various factors, necessitating drugs that can target these diverse components.
Another aspect of BPH treatment that continues to gain popularity is using a multi-drug regimen. As the number of treatments increases, and as those treatments become more mechanistically specific with smaller side effect profiles, the appeal of using multiple medications with complimentary effects will only increase. This will allow physicians to carefully tailor medications to maximize patient quality of life.
However, despite the promising potential of these new treatments, there are challenges that need to be addressed. Many therapies that have demonstrated efficacy in laboratory settings have struggled to replicate the same success in clinical trials. This disconnect can be attributed to various factors, including financial constraints, practicality issues, and unforeseen complications. For instance, the use of rho-kinase inhibitors, which have shown promise in vitro, faces practical hurdles in translating their benefits to clinical settings [125].
Over the next several years, we anticipate the emergence of new drugs that could offer durable and effective treatment options for BPH. To realize this potential, it is crucial for all stakeholders involved in the process to collaborate seamlessly. This collective effort should involve researchers dedicated to exploring new avenues of treatment, pharmaceutical companies committed to developing these therapies, government bodies providing support and regulation, and physicians at the forefront of patient care.
