madman
Super Moderator
Abstract
Benign prostatic hyperplasia affects up to 80% of men in their lifetime. It causes bladder outflow obstruction, leading to lower urinary tract symptoms, which can have a large impact on quality of life. Lifestyle modifications and pharmacotherapy are often offered as first-line treatments for patients. These include alpha blockers, 5-alpha-reductase inhibitors, phosphodiesterase-5 inhibitors, anticholinergics, B3-agonists, and desmopressin. While often well tolerated, these pharmacotherapies do have significant side effects, which both clinicians and patients should understand and discuss in order to make an informed treatment decision among alternatives. The purpose of this review is to provide a current overview of the risks and side effects of commonly used medications in benign prostatic hyperplasia management.
1. Introduction
Conservative lifestyle changes and pharmacologic therapy are the traditional first-line options for men presenting with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).1-5 This approach is supported by well-designed clinical trials with appropriate follow-up, including the Medical Therapy of Prostatic Symptoms (MTOPS) Study and the Combination of Avodart and Tamsulosin (CombAT) study. These seminal papers show an improvement in multiple endpoints, representing decreased progression of the disease, and were a breakthrough in BPH treatment.2,6,7 However, the traditional “one size fits all”approach to BPH, which progresses from initial medical management to surgical intervention, does not factor in individual patient preferences. For many patients, these preferences include minimizing unwanted side effects.
While medical therapies for BPH are generally seen as a lower risk option compared to procedural intervention, clinicians and patients must be aware that this approach is not completely without risk. Medication side effects must be discussed thoroughly with patients when making informed decisions about their healthcare options. This is especially relevant in today's BPH landscape, where minimally invasive surgical techniques (MISTs) are a viable alternative for certain patients. Patients and clinicians should also be aware of the risks associated with delayed intervention, including the potential loss of quality-adjusted life years and changes in bladder function. In this review, we focus on the risks and side effects associated with the medical management of BPH.
2. Alpha-blockers and phosphodiesterase-5 inhibitors
Alpha-1 adrenergic receptor antagonists, also known as alpha-1 blockers, are a first-line medical therapy for male lower urinary tract symptoms secondary to BPH. These medications, not surprisingly, bind to type-1 alpha-adrenergic receptors and inhibit smooth muscle contraction.8 While both alpha-1A and alpha-1B receptors are distributed in various tissues throughout the body, alpha-1B receptors play a significant role in mediating vascular tone.8 Meanwhile, alpha-1A receptors do not, and they are present in the smooth muscle of the genitourinary tracts, predominantly in the prostatic stroma.9 Functionally, blockade of alpha-1A receptors inhibits smooth muscle contraction and reduces the prostate and bladder neck muscle tone.9,10 This reduces the degree of obstruction at the bladder neck and improves symptoms. Building on this mechanistic understanding, the therapeutic and adverse effects of alpha-1 adrenergic blockers depend in part on their degree of selectivity or non selectivity for specific receptor subtypes. The selectivity of these agents is aimed at minimizing unwanted systematic adverse effects on blood pressure.
2.1. Non selective versus selective alpha-1 adrenoceptor antagonists
2.2. Selective alpha-1 adrenoceptor antagonists
2.2.1. Associations between alpha blockers and systemic diseases
2.2.2. Intraoperative floppy iris syndrome
2.3. Phosphodiesterase-5 inhibitors
3. 5ARIs
5ARIs are recommended for the primary medical management of BPH, for prostates greater than 30 cc, in the 2022 CUA Guidelines.44 It has been shown to improve both symptoms and alter the natural course of disease progression, especially in combination with alpha-blockers.5,45
5-Alpha-reductase (5AR) converts testosterone to dihydrotestosterone. There are three isoenzymes: type I is mainly expressed in the skin and liver; type II is predominately expressed in the prostate, seminal vesicles, and epididymis; and type III is ubiquitously expressed.46 Dutasteride inhibits both types I and II, while finasteride inhibits only type I, although clinically major differences in outcomes have not been observed between these two 5ARIs. However, these medications do have side effects that can be significant and bothersome to patients and are in some cases irreversible (Table 2).
3.1. Sexual adverse effects
3.2. Psychiatric adverse effects
3.3. Metabolic syndrome
3.4. Prostate cancer
4. Urgency and nocturia treatments (anticholinergics, beta-3agonist, desmopressin)
Anticholinergics block M2 and M3 muscarinic receptors, thereby suppressing detrusor smooth muscle activity and decreasing storage symptoms.73 This can translate to patient reported improvement in lower urinary tract bother scores in patients with BPH/LUTS.74 However, as with other pharmacologic therapies, there are side effects that affect patient adherence and overall quality of life.
5. Phytotherapies
Phytotherapy, also known as plant-based herbal preparation, has purported benefits in men with LUTS, but there is limited evidence. Common phytotherapeutic agents include Serenoa repens (saw palmetto), Pygeum africanum (African plum bark), Cucurbita pepo, and Urtica dioica.86 Due to conflicting evidence, phytotherapy is not considered a standard treatment for LUTS/BPH and is not recommended by CUA (Canadian Urological Association).87 Similarly, the American Urological Association (AUA) guidelines note that Saw Palmetto fails to provide a clinically meaningful effect on LUTS secondary to BPH.3,88
6. Opportunity cost: QALY, bladder function changes, and cost
A final effect that patients should be aware of when making decisions about their treatment for BPH is the opportunity cost of proceeding with medical management. Certain patients who are apprehensive about procedures for BPH may experience years of reduced urinary and overall quality of life due to suboptimal voiding or side effects during medical management. Of course, these considerations must be carefully balanced against the risks of side effects from procedures and individualized for every patient.
7. Conclusions
This review provides a contemporary overview of risks and side effects in the medical management of BPH. Medical management options for BPH can be effective in alleviating symptoms and are deemed relatively low-risk first-line modalities appropriate for many patients or patients who prefer nonsurgical management of BPH. However, it is crucial to discuss the potential risks and side effects associated with pharmacologic therapy for BPH with patients. These detailed conversations are critical to ensure that patients understand their options in order to proceed with treatments that are most aligned with their individual goals.
Benign prostatic hyperplasia affects up to 80% of men in their lifetime. It causes bladder outflow obstruction, leading to lower urinary tract symptoms, which can have a large impact on quality of life. Lifestyle modifications and pharmacotherapy are often offered as first-line treatments for patients. These include alpha blockers, 5-alpha-reductase inhibitors, phosphodiesterase-5 inhibitors, anticholinergics, B3-agonists, and desmopressin. While often well tolerated, these pharmacotherapies do have significant side effects, which both clinicians and patients should understand and discuss in order to make an informed treatment decision among alternatives. The purpose of this review is to provide a current overview of the risks and side effects of commonly used medications in benign prostatic hyperplasia management.
1. Introduction
Conservative lifestyle changes and pharmacologic therapy are the traditional first-line options for men presenting with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).1-5 This approach is supported by well-designed clinical trials with appropriate follow-up, including the Medical Therapy of Prostatic Symptoms (MTOPS) Study and the Combination of Avodart and Tamsulosin (CombAT) study. These seminal papers show an improvement in multiple endpoints, representing decreased progression of the disease, and were a breakthrough in BPH treatment.2,6,7 However, the traditional “one size fits all”approach to BPH, which progresses from initial medical management to surgical intervention, does not factor in individual patient preferences. For many patients, these preferences include minimizing unwanted side effects.
While medical therapies for BPH are generally seen as a lower risk option compared to procedural intervention, clinicians and patients must be aware that this approach is not completely without risk. Medication side effects must be discussed thoroughly with patients when making informed decisions about their healthcare options. This is especially relevant in today's BPH landscape, where minimally invasive surgical techniques (MISTs) are a viable alternative for certain patients. Patients and clinicians should also be aware of the risks associated with delayed intervention, including the potential loss of quality-adjusted life years and changes in bladder function. In this review, we focus on the risks and side effects associated with the medical management of BPH.
2. Alpha-blockers and phosphodiesterase-5 inhibitors
Alpha-1 adrenergic receptor antagonists, also known as alpha-1 blockers, are a first-line medical therapy for male lower urinary tract symptoms secondary to BPH. These medications, not surprisingly, bind to type-1 alpha-adrenergic receptors and inhibit smooth muscle contraction.8 While both alpha-1A and alpha-1B receptors are distributed in various tissues throughout the body, alpha-1B receptors play a significant role in mediating vascular tone.8 Meanwhile, alpha-1A receptors do not, and they are present in the smooth muscle of the genitourinary tracts, predominantly in the prostatic stroma.9 Functionally, blockade of alpha-1A receptors inhibits smooth muscle contraction and reduces the prostate and bladder neck muscle tone.9,10 This reduces the degree of obstruction at the bladder neck and improves symptoms. Building on this mechanistic understanding, the therapeutic and adverse effects of alpha-1 adrenergic blockers depend in part on their degree of selectivity or non selectivity for specific receptor subtypes. The selectivity of these agents is aimed at minimizing unwanted systematic adverse effects on blood pressure.
2.1. Non selective versus selective alpha-1 adrenoceptor antagonists
2.2. Selective alpha-1 adrenoceptor antagonists
2.2.1. Associations between alpha blockers and systemic diseases
2.2.2. Intraoperative floppy iris syndrome
2.3. Phosphodiesterase-5 inhibitors
3. 5ARIs
5ARIs are recommended for the primary medical management of BPH, for prostates greater than 30 cc, in the 2022 CUA Guidelines.44 It has been shown to improve both symptoms and alter the natural course of disease progression, especially in combination with alpha-blockers.5,45
5-Alpha-reductase (5AR) converts testosterone to dihydrotestosterone. There are three isoenzymes: type I is mainly expressed in the skin and liver; type II is predominately expressed in the prostate, seminal vesicles, and epididymis; and type III is ubiquitously expressed.46 Dutasteride inhibits both types I and II, while finasteride inhibits only type I, although clinically major differences in outcomes have not been observed between these two 5ARIs. However, these medications do have side effects that can be significant and bothersome to patients and are in some cases irreversible (Table 2).
3.1. Sexual adverse effects
3.2. Psychiatric adverse effects
3.3. Metabolic syndrome
3.4. Prostate cancer
4. Urgency and nocturia treatments (anticholinergics, beta-3agonist, desmopressin)
Anticholinergics block M2 and M3 muscarinic receptors, thereby suppressing detrusor smooth muscle activity and decreasing storage symptoms.73 This can translate to patient reported improvement in lower urinary tract bother scores in patients with BPH/LUTS.74 However, as with other pharmacologic therapies, there are side effects that affect patient adherence and overall quality of life.
5. Phytotherapies
Phytotherapy, also known as plant-based herbal preparation, has purported benefits in men with LUTS, but there is limited evidence. Common phytotherapeutic agents include Serenoa repens (saw palmetto), Pygeum africanum (African plum bark), Cucurbita pepo, and Urtica dioica.86 Due to conflicting evidence, phytotherapy is not considered a standard treatment for LUTS/BPH and is not recommended by CUA (Canadian Urological Association).87 Similarly, the American Urological Association (AUA) guidelines note that Saw Palmetto fails to provide a clinically meaningful effect on LUTS secondary to BPH.3,88
6. Opportunity cost: QALY, bladder function changes, and cost
A final effect that patients should be aware of when making decisions about their treatment for BPH is the opportunity cost of proceeding with medical management. Certain patients who are apprehensive about procedures for BPH may experience years of reduced urinary and overall quality of life due to suboptimal voiding or side effects during medical management. Of course, these considerations must be carefully balanced against the risks of side effects from procedures and individualized for every patient.
7. Conclusions
This review provides a contemporary overview of risks and side effects in the medical management of BPH. Medical management options for BPH can be effective in alleviating symptoms and are deemed relatively low-risk first-line modalities appropriate for many patients or patients who prefer nonsurgical management of BPH. However, it is crucial to discuss the potential risks and side effects associated with pharmacologic therapy for BPH with patients. These detailed conversations are critical to ensure that patients understand their options in order to proceed with treatments that are most aligned with their individual goals.
