ABSTRACT

Benign prostatic hyperplasia (BPH) is among the commonest urological abnormalities affecting the aging male. The cause of the increase in prostatic volume is multifactorial, but current research has implicated hormonal aberrations. Clinical assessment of the patient is integral to determining the optimal treatment strategy. Exclusion of prostatic cancer and complications of BPH are critical prior to the commencement of conservative and non-invasive strategies. Recently, the introduction of pharmaceutical agents has changed the landscape of management of BPH. Alpha-blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors provide significant symptomatic improvement for BPH, particularly when used in combination. Invasive surgical therapies remain the gold standard for refractory and complicated BPH disease. Advances in technology have provided new methods to perform prostatectomy including: bipolar resection, laser resection, ablation, enucleation or vaporization. Newer, minimally invasive measures have been introduced in an attempt to limit patient morbidity, specifically operative complications, sexual and urinary function. While results are promising, these emerging therapies have limited long-term data. The purpose of the current chapter is to provide an overview of the current knowledge of benign prostatic hyperplasia. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

INTRODUCTION

The prostate is an organ linked inextricably to the endocrine system. During the development of the prostate, the epithelium and mesenchyme are under the control of testicular androgens, and interact to form an organized secretory organ. Furthermore, the endocrine system plays a key mechanistic role in many prostate diseases, and many therapies for prostatic diseases are aimed at the manipulation of the endocrine system. The gland resides in the true anatomical pelvis and forms the most proximal aspect of the urethra. It has been stated that the prostate gland is the male organ most commonly afflicted with either benign or malignant neoplasms (1). Therefore, it is an organ with which every physician and surgeon needs to be familiar. We will focus on BPH, the most prevalent of benign disorders affecting the prostate.

EMBRYOLOGY

The development, growth and cytodifferentiation of the prostate are androgen-dependent and occur via embryonic cell-to-cell interactions between the mesenchyme (undifferentiated connective tissue) that induce epithelial development while the epithelium induces mesenchymal differentiation (2).

In the developing prostate, urogenital sinus mesenchyme acting under the influence of testicular androgens induces ductal morphogenesis, the expression of epithelial androgen receptors, regulates epithelial proliferation and specifies the expression of prostatic-lobe specific secretory proteins. The developing prostatic epithelium reciprocally induces the differentiation and morphological patterning of smooth muscle in the urogenital sinus mesenchyme (2). In the prostate, it is traditional to consider androgens as promoters of growth, while activin and tumor growth factor-beta1 (TFG-β1) are regarded as potent growth inhibitors. These factors do not act independently, however, and cross-talk occurs between the signaling pathways at a sub-cellular level (3).

The first step in development of the prostate begins with the urogenital sinus mesenchyme signaling to the epithelium, causing it to form epithelial buds. Androgens then induce bud elongation, branching and epithelial differentiation (3). Prenatally, the androgen receptor (AR) is expressed only in the mesenchyme, not in the epithelium. Initial epithelial development is thus controlled via paracrine interactions where activation of stromal androgen receptors stimulates growth factors and induces growth in adjacent prostatic epithelial cells (4).

At the 5^th week, the mesonephric (Wolffian) duct opens onto the lateral surface of the urogenital sinus and gives rise to the ureteric bud (Figure 1). By the 7^th week, the growth of the urogenital sinus involves the progressive incorporation of the terminal part of the mesonephric duct into the wall of the urogenital sinus. They eventually open into the Mullerian tubercle that is the future verumontanum of the prostate. At their termination the paramesonephric (Mullerian) ducts fuse and are surrounded by the mesonephric ducts. At 10 weeks, prostatic epithelial buds begin to arise from the circumference of the urethra, around the orifice of the paramesonephric ducts. They develop predominantly on the posterior surface of the junction of the mesonephric ducts, forming two concentrations, above and below them (5).

Figure 1.

The embryological origin and development of the prostatic urethra and the prostate, adapted from Delmas (5).

During the fetal period at about 6 months, multiple outgrowths arise from the prostatic portion of the urethra, particularly the posterior surface of the urethra, and grow into the surrounding mesenchyme. Glandular epithelium of the prostate differentiates from the endodermal cells of the urethra, and outgrowths of glandular epithelium protrude into the associated mesenchyme differentiate into the dense stroma and smooth muscle fibers of the prostate. In contrast, the prostatic glandular epithelium outgrowths situated on the anterior surface regress and are replaced by fibromuscular tissue. This region becomes the future anterior commissure of the prostate 5,6).

ANATOMY

According McNeal’s model of the prostate (7), four different anatomical zones may be distinguished that have anatomo-clinical correlation (Figure 2):

1.

The peripheral zone: is the area forming the postero-inferior aspect of the gland and represents 70% of the prostatic volume. It is the zone where the majority (60-70%) of prostate cancers form.

2.

The central zone: represents 25% of the prostate volume and contains the ejaculatory ducts. It is the zone which usually gives rise to inflammatory processes (e.g., prostatitis).

3.

The transitional zone: this represents only 5% of the total prostatic volume. This is the zone where benign prostatic hypertrophy occurs and consists of two lateral lobes together with periurethral glands. Approximately 25% of prostatic adenocarcinomas also occur it this zone.

4.

The anterior zone: predominantly fibromuscular with no glandular structures.

The prostate weighs approximately 20g by the age of 20 and has the shape of an inverted cone, with the base at the bladder neck and the apex at the urogenital diaphragm (8). The prostatic urethra does not follow a straight line as it runs through the center of the prostate gland but it is actually bent anteriorly approximately 35 degrees at the verumontanum (where the ejaculatory ducts join the prostate) (9).

Figure 2.

1= Peripheral Zone, 2= Central Zone, 3= Transitional Zone, 4= Anterior Fibromuscular Zone. B= Bladder, U= Urethra, SV= Seminal Vesicle (adapted from Algaba (10)).

HISTOLOGY

The prostate consists of stromal and epithelial elements. Smooth muscle cells, fibroblasts and endothelial cells are in the stroma and the epithelial cells are secretory cells, basal cells and neuroendocrine cells (Figure 3).

Figure 3.

Histology of a prostate gland affected by benign prostatic hyperplasia.

The columnar secretory cells are tall with pale to clear cytoplasm. These cells stain positively with prostate-specific antigen (PSA) (11). Basal cells are less differentiated than secretory cells and are devoid of secretory products such as PSA (12). Finally, neuroendocrine cells are irregularly distributed throughout ducts and acini, with a greater proportion in the ducts. The prostate has the greatest number of neuroendocrine cells of any of the genitourinary organs (13). Glands are structured with open and closed cell types with the open type facing the inside of the duct having a monitoring role over its contents. Most cells contain serotonin, but other peptides that are present include somatostatin, calcitonin, gene-related peptides and katacalcin (11). The cells co-express PSA and prostatic acid phosphatase. Their function is unclear, but it is speculated that these cells are involved with local regulation by paracrine release of peptides (11). Prostatic ducts and acini are distinguished by architectural pattern at low power magnification. The prostate becomes more complex with ducts and branching glands arranged in lobules and surrounded by stroma with advancing age.

Figure 4.

Diagram outlining the structure of the prostate gland with regard to ducts, glandular cells and their relationship to blood vessels.

PHYSIOLOGY

At present, there is only limited knowledge of all of the secretory products of the prostate and how these relate to reproduction and infertility. However, the main role of the prostate as a male reproductive organ is to produce prostatic fluid that accounts for up to 30 per cent of the semen volume. Prostatic fluid promotes sperm motility, and it is a milky, alkaline fluid containing PSA, citric acid, calcium, zinc, acid phosphatase and fibrinolysin among its many constituents (Table 1) (14). During ejaculation, alpha-adrenergic stimulation of prostatic smooth muscle expresses seminal fluid containing sperm from the ampulla of the vas deferens into the posterior urethra (15). Interestingly, abnormal growth of the prostate is only experienced by humans and dogs, and why other mammals are spared is a mystery (16).

ENDOCRINE CONTROL OF PROSTATIC GROWTH

Intraprostatic signaling systems are important for the regulation of cell proliferation and extracellular matrix production in the prostatic stroma. Central to this premise is the balance between factors such as TGF-β1, that induces extracellular matrix production, suppresses collagen breakdown and cell proliferation and factors such as fibroblast growth factor 2 and insulin-like growth factors that are mitogenic in the stromal compartment (18). Other endocrine pathways are being investigated, and there is a growing body of evidence suggesting an abnormality in the insulin-like growth factor axis is playing a role in the pathogenesis of BPH (19).

Testosterone

Prostatic epithelial cells express the androgen receptor (20). From the beginning of embryonic differentiation to pubertal maturation and beyond, androgens are a prerequisite for the normal development and physiological control of the prostate (21). Androgens help maintain the normal metabolic and secretory functions of the prostate, and they are also implicated in the development of BPH and prostate cancer. Androgens do not act in isolation, and other hormones and growth factors are being investigated (22).

Androgens also interact with prostate stromal cells which release soluble paracrine factors that induce growth and development of the prostatatic epithelium (4). These paracrine pathways might be critical in regulating the balance between proliferation and apoptosis of prostate epithelial cells in the adult (22).

The appropriate balance between testosterone and its 5-alpha reduced metabolites is key to normal prostate physiology (note the metabolic pathways for androgen metabolism are described in Endotext, Endocrinology of Male Reproduction, Androgen Physiology, Pharmacology and Abuse, D Handelsman). The metabolism of testosterone to dihydrotestosterone (DHT) and its aromatization to estradiol are recognized as the key events in prostatic steroid response.

Figure 5.

Conversion of testosterone to dihydrotestosterone (DHT) by 5alpha reductase

Testosterone, to be maximally active in the prostate, must be converted to DHT by the enzyme 5-alpha reductase (Figure 5) (23). DHT has a much greater affinity for the androgen receptor than does testosterone, and DHT accumulates in the prostate even when circulating concentrations of testosterone are low (24,25). Based on rat studies, DHT is about twice as potent as testosterone at equivalent androgen concentrations (26). Therefore, prostatic DHT concentrations may remain similar to those in young and elderly men, despite the fact that serum testosterone concentrations generally decline with age (23). In the prostate, the total level of testosterone is 0.4 ng/g and the total of DHT is 4.5 ng/g (27). The total serum concentration of testosterone in the blood is approximately 10 times higher than DHT (17). Circulating DHT, by virtue of its low serum plasma concentration and tight binding to plasma proteins, is of diminished importance as a circulating androgen affecting prostate growth (16). Intra-prostatic androgens are remarkably independent of serum concentrations (28), and circulating androgen concentrations often do not correlate with intraprostatic concentrations (29).

BENIGN PROSTATIC HYPERPLASIA (BPH)

BPH is an age-related and progressive neoplastic condition of the prostate gland (36). BPH can only be diagnosed definitively by histology. BPH in the clinical setting is characterized by lower urinary tract symptoms (LUTS, see below and Table 2). There is no causal relationship between BPH and prostate cancer (37). Clinically apparent BPH has a significant effect on quality of life, particularly its effects on nocturia and bladder dysfunction. The overall prevalence of BPH is 10.3%, with an overall annual incidence rate of 15 per 1000 man-years, increasing with age (3 per 1000 at age 45-49 years, to 38 per 1000 at 75-79 years). For a symptom-free man at age 46, the 30-year risk of clinical BPH is 45% (38). The true prevalence and incidence of clinical BPH will vary according to the criteria used to describe the condition; however, it has been estimated that the prevalence of BPH is rising due to increases in modifiable risk factors such as obesity (39). It is crucial to acknowledge that LUTS can exist without signs of BPH – as the symptoms can be caused by variations in the sympathetic nervous stimulation of prostatic smooth muscle, variability of prostatic anatomy (viz., enlarged median lobe of the prostate), and the variable effects of bladder physiology from the obstruction and aging.

There have been several studies demonstrating the fact that clinical BPH is a progressive disease. The Olmsted county study (40) showed that with each year there were deteriorations in symptom scores, peak flow rates, and increases in prostate volumes based on transrectal ultrasound scanning (TRUS). The risk of acute urinary retention (AUR) increased with flow rates below 12 ml/sec and with glands greater than 30ml. Studies have also demonstrated that those with larger prostates (>40 ml) and with serum PSA greater than 1.4 ng/ml were more likely to develop acute urinary retention (41). Treatment, however, has changed with the advent of effective non-surgical therapies. Between 1992-1998 there has been a significant lengthening of the period between first diagnosis of LUTS secondary to clinical BPH and surgery, associated with the earlier and increased use of specific medical treatments (42). From the patients perspective, the goals of therapy are to improve quality of life, reduce symptoms, and avoid surgery while ensuring safety from the complications of BPH (43).

PATHOPHYSIOLOGY OF BPH

DISEASE MANIFESTATIONS OF BPH

Lower Urinary Tract Symptoms (LUTS)

Lower urinary tract symptoms (LUTS) are highly prevalent and the majority of LUTS in men is produced by BPH, but may be contributed to by a variety of conditions (Figure 6). LUTS are traditionally divided into voiding or obstructive and storage or irritative symptoms (Table 2). Voiding symptoms are more common, however it is storage symptoms that are most bothersome and have a greater impact on a patient's life (64,65). The prevalence of clinical BPH rises with age and approximately 25% of men age 40 or over will suffer from LUTS (66).

Figure 6.

Interaction of the many factors involved in the pathogenesis of LUTS. Other causes of LUTS (top right) include all of the differential diagnoses included in Table 5 (see below).

Table 2.

Lower Urinary Tract Symptoms

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Voiding or Obstructive Symptoms	Storage or Irritative Symptoms
Hesitancy Poor stream Intermittent stream Straining to pass urine Prolonged micturition Sense of incomplete bladder emptying Terminal dribbling	Urinary frequency Urgency Urge incontinence Nocturia

In the past, LUTS suggestive of bladder outflow obstruction (BOO) secondary to BPH were referred to as ‘prostatism’, once other causes such as a urinary tract infection or prostate cancer were excluded. The pathology behind the symptoms was thought to be obstruction due to prostatic gland enlargement alone. However, it is now recognized that voiding/obstructive symptoms result from direct urinary flow obstruction whilst storage/irritative symptoms appear to be due to secondary bladder dysfunction (67). Thus, LUTs occurs after the prostate enlargement causes obstruction, and the bladder voiding is secondarily affected leading irritable symptoms (Figure 7).

Figure 7.

Diagrammatic representation of BPH with the enlarged prostate transition zone causing obstruction of the prostatic urethra and the secondary changes in the bladder leading to hypertrophy of the detrusor muscle (copyright Nathan Lawrentschuk 2012).

This concept has been further refined in that obstructive symptoms are thought to result not only from mechanical obstruction due to glandular enlargement, but also dynamic obstruction secondary to contraction of the smooth muscle of the prostate, urethra and bladder neck. This dynamic obstruction is a result of sympathetic nervous system mediated stimulation of alpha-1 adrenoceptors. Storage symptoms appear to be caused by detrusor instability related to detrusor muscle changes in response to obstruction, such as bladder wall hypertrophy and collagen deposition in the bladder (68,69). Adrenoceptors may be further sub-divided into alpha1A and alpha1D subtypes, with alpha1A predominant in the prostate and alpha 1D in the bladder. Thus, blockade of alpha1A may be necessary for reduction of obstruction whereas the blockade of alpha1D may be required to relieve storage symptoms (70) (see below).

It has been suggested that the etiology of LUTS related to BPH is even more complex than outlined above, with extra-prostatic mechanisms such as bladder wall ischemia and changes in the central nervous system being implicated (71). Normal lower urinary tract function is complex, and theoretically any disruption of the pathway for micturition (Figure 8 below) may lead to LUTS (72).

It is worth noting the relationship between LUTS and sexual dysfunction, with sexual dysfunction being highly prevalent in men with LUTS (73). By sexual dysfunction, we refer to decreased libido, erectile dysfunction, decreased ejaculation and other ejaculation disorders. Kassabian (74) expands on the relationship and agrees with Leilefeld et al (75) in suggesting that the relationship is coincidental and both are common in the ageing male.

Figure 8

- Normal micturition pathways (reproduced with permission from Physiology and pathophysiology of lower urinary tract symptoms, Drugs of Today, Vol 37, p. 7, Michel MC(72)).

COMPLICATIONS OF BPH

The complications of BPH are summarized in Table 3.

HISTORY

A comprehensive medical history must be evaluated and should include the use of a voiding diary, the International Prostate Symptom Score (IPSS) and a discussion of the role of PSA testing (94). An outline of the evaluation and treatment options for LUTS is shown in Table 4 and is discussed in greater depth below (95,96). Previous urological disease should be documented including previous urological surgery, UTI, bladder or renal calculi, renal disease and penoscrotal pathology. Any risk factors for surgery such as diabetes mellitus, immunosuppression, ischemic heart disease, respiratory problems, smoking as well as a comprehensive list of medications should be noted. Medications with anti-cholinergic properties should be noted, as these may contribute to the patient’s symptoms. The use of antihypertensives must be noted as any alpha-blocker treatment initiated could potentially cause severe hypotension.

As discussed in the section on differential diagnosis, consideration needs to be given to neurologic causes of voiding dysfunction such as stroke or Parkinson’s disease.

International Prostate Symptom Score (IPSS)

The American Urologic Association (AUA) Symptom Index was developed as a standardized instrument to assess the degree of bladder outlet obstruction in men (89). It is widely used and consists of seven questions that assess emptying, frequency, intermittency, urgency, weak stream and straining with each graded with a score of 0-5. Total score ranges 0-35. The index categorizes patients as:

1.

Mild (score ≤7)

2.

Moderate (score 8-19)

3.

Severe (score 20-35).

The International Prostate Symptom Score (IPSS) is a modification of the AUA Symptom Index adding a single question assessing the quality of life or bother score based on the patient’s perception of the problem (Figure 9) (97). Both the AUA and IPSS questionnaires, although not specific for BPH, prostate volume, urinary flow rate, post-void residual volume, or bladder outlet obstruction, have been validated and are sensitive enough to be to be used in the evaluation of symptoms and selection of treatment (98-100). Many would argue that the score is the primary determinant of whether or not a patient proceeds to further treatment. Further, these questionnaires are a valuable objective measure when determining the response to treatments for BPH.

Figure 9.

International Prostate Symptom Score (IPSS) Sheet (101,102)

EXAMINATION

General appearance is of importance, especially in identifying those with neurological disease (e.g., past stroke, Parkinson’s disease) or other major co-morbidities (obesity, severe osteoarthritis, diabetes) that may impact on treatment or further investigation. An abdominal examination should identify those in marked urinary retention, any abnormal masses, and previous surgical scars. A careful assessment of the scrotum and its contents as well as the penis is also warranted to exclude any other pathology. The digital rectal examination (DRE) is important in identifying prostatic abnormalities, including clinically apparent prostate carcinoma (103). Prostate size, texture, and tenderness should all be assessed, as should anal tone. Any nodules should be carefully noted. Constipation may also be a contributing factor to urinary retention and anal tone should also be recorded.

DIFFERENTIAL DIAGNOSIS OF BPH

It is important to acknowledge that the diagnosis of BPH often relies on surrogate measures until a histological diagnosis is confirmed. These range from clinical (symptom scores), physiological (uroflowmetry), anatomical (prostatic volume on DRE or TRUS) and biochemical (PSA values) measurement. Although all of these measurements capture some component of BPH, none of them is specific for BPH (104). Surrogate measures are likely to represent a continuum of disease severity without the existence of a threshold. Thus, differential diagnoses need to always be considered and where appropriate, excluded. In table 5 below, some of the more obvious differential diagnoses are listed, but will not be examined in detail.

PROSTATITIS

Prostatitis is a common condition that must be excluded from other causes of LUTS and is a common cause of visits to primary care physicians and urologists. It may present as an acute bacterial infection or may be chronic, occasionally progressing to a debilitating illness. In practice, the clinical diagnosis of prostatitis depends on the history and physical examination, but there is no characteristic physical finding or diagnostic laboratory test. Patients with prostatitis experience considerable morbidity and may remain symptomatic for many years. Unfortunately, there is limited understanding of the pathophysiology and optimal treatment for most patients. Prostatitis has been sub-classified and an abbreviated version is shown in Table 6.

INVESTIGATIONS OF LUTS

As outlined by Tubarro et al (94), the aim of investigations for LUTS should be threefold: (1) to evaluate the possible relationship between prostatic enlargement, lower urinary tract symptoms and signs of bladder outlet obstruction; (2) to quantify the severity of benign prostatic enlargement-related symptoms and signs and (3) to rule out the presence of a prostate cancer.

Urinary Flow Rate (Uroflowmetry)

Uroflowmetry is considered by some as the single most useful urodynamic technique for the assessment of obstructive uropathy. The purpose of the uroflow examination is to record one or more micturitions that are representative of the patient’s usual voiding pattern. Therefore, more than one micturition is often required and it is necessary to confirm with the patient if the flow was better, worse or about the same as their normal pattern, otherwise intra-individual variability may lead to false assumptions (111). The study may be performed in the office or as part of other urodynamic studies in the laboratory or operating suite.

Figure 10 indicates the most common urinary flow parameters measured. Of these, the peak flow rate is the most closely correlated with the extent of outflow obstruction (Table 10). Total voiding time is prolonged in obstruction and has a reduced Qmax. Poor detrusor contractility is impossible to distinguish from bladder outflow obstruction on uroflowmetry so other urodynamics investigations such as a cytometry are indicated.

Figure 10.

Uroflowmetry in a normal individual- diagram above and actual reading below (Table 10).

Table 10.

Interpretation of Uroflowmetry Results.

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Flow rate- Qmax	Interpretation
>15ml/sec	Unlikely to be significant obstruction
<10ml/sec	Likely to be significant obstruction or weak detrusor activity
10-15ml/sec	Equivocal

OVERVIEW OF TREATMENT OF BPH

The primary aim of any treatment for BPH in the vast majority of men is to relieve bothersome obstructive and irritative symptoms (114) (Table 2). Treatment is often undertaken on an elective basis for such patients. Those in whom complications of BPH occur have treatment done urgently as a matter of course. A range of treatment options are available and may be tailored to the needs of every individual, taking into account their disease manifestations, success rates of treatment, possible complications, and patient preference.

WATCH AND WAIT/LIFESTYLE CHANGE

Many men who present with LUTS are often seeking a full assessment of their prostatic health rather than immediate treatment of symptoms that may not be exceptionally bothersome. People with mild symptoms may wish to pursue lifestyle changes as a way of improving their quality of life but with the option of review if such measures fail or symptoms worsen. Furthermore, when an adequate history is taken, hidden agendas such as fear of prostate cancer may even be revealed and fears allayed.

Often drinking habits may be responsible for symptoms such as nocturia, where considerable fluid volumes are consumed in the evening. Reducing fluid intake may diminish nocturia and evening urgency. Furthermore, caffeine and alcohol acting as diuretics can further exacerbate LUTS. Simple shifts in daily fluid intake may fulfil patient expectations and result in satisfactory outcomes. Voiding diaries are useful for making patients aware of drinking habits and may be the catalyst for initiating and monitoring changes. Bladder retraining (by using timed voiding, strengthening pelvic floor exercises, and monitoring oral intake) is also an option in some individuals, once a voiding diary has been examined.

Medications may also play a role with LUTS. Measures such as diuretic restriction in evenings often prevents nocturia and frequency, provided the diuretic can be taken earlier in the afternoon.

It is important to discuss options with the patient and that they he be made aware that the possibility of damage to their upper urinary tract or to the detrusor muscle may result if their symptoms deteriorate and they do not seek medical attention.

PHYTOTHERAPY FOR BPH

Phytotherapy, or the use of plant extracts, is becoming widely used in the management of many medical conditions including BPH (Table 11) (115). Often these agents are promoted to aid “prostatic health” and a significant proportion of men try them. Factors also contributing to their widespread use include the perception that they are supposedly ''natural'' products; the presumption of their safety (although this is not adequately proven); their alleged potential to assist in avoiding surgery, and even the unproven claim that they may prevent prostate cancer. The widespread availability of these products (without prescription) in vitamin shops, supermarkets, pharmacies, and over the internet has contributed to their usage and reflects the demand for these phytotherapeutic agents. The mechanisms of action are poorly understood but have been proposed to be (1) anti-inflammatory, (2) inhibitors of 5-alpha reductase, and more recently (3) through alteration in growth factors (116).

Phytotherapy, although promising, lacks long-term, good quality clinical data (117). Nevertheless, because there is a large placebo effect associated with treatment of voiding symptoms, the use of herbal products that have few or no side effects may be a reasonable first-line approach for many patients (118). However, patients should be counselled that the efficacy, mechanisms of action and long-term effects of these agents are not known and they must be aware of the limitations before proceeding (119).

The most popular phytotherapeutic agents are extracted from the seeds, barks and fruits of plants. Products may contain extracts from one or more plants and different extraction procedures are often used by manufacturers. Thus, the composition and purity of products may differ even if they originated from the same plant. Basic research on one product may not be easily transferred to another making the gathering of data and giving of advice difficult (120).

MEDICAL THERAPY FOR BPH – MONOTHERAPY AGENTS

In 1986, Caine (62) proposed that infravesical obstruction in men with symptomatic BPH comprised both static and dynamic components. The static component of obstruction is related primarily to the mechanical obstruction caused by the enlarging prostatic adenoma whereas the dynamic component is principally determined by the tone of the prostatic smooth muscle. Two avenues for pharmacotherapy have therefore evolved, namely shrinking the prostate tissue or relaxing the smooth muscle of the prostate. Prostatic smooth muscle tone is under the influence of the autonomic nervous system. Thus, any pharmacologic agent that may interfere with the functioning of this system could alter resistance in smooth muscle tone and resulting symptoms.

Medical therapy is now first-line treatment for most men with symptomatic BPH. They are non-invasive, reversible, cause minimal side effects, and significantly improve symptoms (81,136). With these recommendations, the rates of prescriptions for the medical management for BPH have increased drastically over the past decade (137,138). This increased interest has further led to the development of safer, more efficacious agents.

MAJOR STUDIES OF MEDICAL TREATMENT OF BPH

The medical treatment of clinical BPH has come under increasing scrutiny through larger trials that have become imperative for their introduction into clinical practice. Some of these larger trials have been selected and are discussed below.

EMERGING COMBINATION THERAPY REGIMES

With the increasing body of evidence supporting the use of PDE5 inhibitors in the setting of BPH, a number of trials support its use in combination therapy. To date, there are smalls studies of alfuzosin and tadalafil, tamsulosin and sildenafil, and tamsulosin and vardenafil. These early studies suggest that combination therapy is more effective than monotherapy for urinary and erectile function with a good safety profile (195,196). A meta-analysis of 11 randomized controlled trials (n=855) looked at alpha blockers with or without PDE5 inhibitors. This analysis found men receiving PDE5 inhibitors had a mean improvement of 1.66 points on IPSS, mean increase of 0.94 ml/s maximum urinary flow rate, and improved erectile function (197). Larger series with longer-term follow up is required to definitively define the role of these combination therapies in current practice.

SURGICAL TREATMENT OF BPH

MEASURING OUTCOMES AND EFFECTIVENESS OF TREATMENT

When considering the effectiveness of any treatment for BPH, one must consider the efficacy and tolerability of invasive or medical therapies (i.e., the effect on both subjective symptoms and urinary flow and incidence of adverse effects), the long-term effectiveness, the impact on daily life activities (quality of life) and the costs (268). Large scale randomized controlled trials provide information on the tolerability and efficacy of treatment options and evidence-based databases such as Cochrane reviews, may further analyze evidence-based data from multiple trials.

CONCLUSION

In conclusion, BPH is a common urological condition that is increasing in incidence in conjunction with the aging male population. If left untreated, BPH can lead to lower urinary tract obstructive symptoms that can significantly affect the quality of life of men.

As outlined in this chapter, the diagnosis of BPH begins with a detailed history of presenting complaint and interrogation of any lower urinary tract signs or symptoms. Questionnaires such as the IPSS score can help quantify the severity of these symptoms along with a uroflowmetry and PVR scan. A urinalysis, serum creatinine, and serum PSA should be ordered to investigate for prostate cancer, UTI, and renal failure. Imaging with USS or CT is not indicated unless there is concurrent hematuria, UTI, or urolithiasis.

Several options are now available for the treatment of BPH. Non-surgical management consists of medications such as alpha-blockers, 5-alpha reductase inhibitors, and PDE5 inhibitors which are available as monotherapy or in combination. BPH refractory to medical management is treated with surgical management which includes invasive and minimally invasive procedures. TURP remains the most widely used procedure for surgical BPH management and simple prostatectomies are reserved for larger prostates, complicated BPH or if TURP cannot be performed. These two procedures form the gold standard of treatment. Laser treatments when available offer good patient outcomes and have potential benefits when compared to TURP. The decision for either of these modalities of treatment is still largely dependent on availability and surgeon experience. The majority of minimally invasive treatment options are still experimental however may have a potential benefit for carefully selected men.

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