eMedicine Specialties > Urology > Benign Prostatic Hypertrophy

Prostate Hyperplasia, Benign: Treatment & Medication

Author: Raymond J Leveillee, MD, FRCS(Glasg), Professor of Clinical Urology, Radiology and Biomedical Engineering, Department of Urology, University of Miami Miller School of Medicine; Chief, Division of Endourology/Laparoscopy and Minimally Invasive Surgery, Department of Urology, Jackson Memorial Hospital
Coauthor(s): Vipul R Patel, MD, Consulting Surgeon, Global Robotics Institute, Florida Hospital Celebration Health; Vincent G Bird, MD, Assistant Professor of Clinical Urology, University of Miami, Miller School of Medicine; Consulting Staff, Department of Urology, Division of Endourology/Laparoscopy and Minimally Invasive Surgery, University of Miami Miller School of Medicine/Jackson Memorial Hospital; Charles R Moore, MD, Fellow, Department of Urology, University of Miami
Contributor Information and Disclosures

Updated: Jun 8, 2009

Treatment

Medical Care

Patients with mild symptoms (IPSS/AUA-SI score <7) or moderate-to-severe symptoms (IPSS/AUA-SI score >8) of benign prostatic hyperplasia (BPH) who are not bothered by their symptoms and are not experiencing complications of BPH should be managed with a strategy of watchful waiting. In these situations, medical therapy is not likely to improve their symptoms and/or QOL. In addition, the risks of treatment may outweigh any benefits. Patients managed expectantly with watchful waiting are usually re-examined annually.

Transurethral resection of the prostate (TURP) has long been accepted as the criterion standard for relieving bladder outlet obstruction (BOO) secondary to BPH. In current clinical practice, most patients with BPH do not present with obvious surgical indications; instead, they often have milder lower urinary tract symptoms (LUTS) and, therefore, are initially treated with medical therapy.

The era of medical therapy for BPH dawned in the mid 1970s with the use of nonselective alpha-blockers such as phenoxybenzamine. The medical therapeutic options for BPH have evolved significantly over the last 3 decades, giving rise to the receptor-specific alpha-blockers that comprise the first line of therapy.

Rationale for alpha-1-receptor blockade in benign prostatic hyperplasia

A significant component of LUTS secondary to BPH is believed to be related to the smooth-muscle tension in the prostate stroma, urethra, and bladder neck. The smooth-muscle tension is mediated by the alpha-1-adrenergic receptors; therefore, alpha-adrenergic receptor–blocking agents should theoretically decrease resistance along the bladder neck, prostate, and urethra by relaxing the smooth muscle and allowing passage of urine. BPH is predominantly a stromal proliferative process, and a significant component of prostatic enlargement results from smooth-muscle proliferation. The stromal-to-epithelial ratio is significantly greater in men with symptomatic BPH than in those with asymptomatic BPH.

The 3 subtypes of the alpha-1 receptor include 1a, 1b, and 1c. Of these, the alpha-1a receptor is most specifically concentrated in the bladder neck and prostate. Provided that the alpha-1a subtype is predominant in the prostate, bladder neck, and urethra, but not in other tissues, drugs that are selective for this receptor (ie, tamsulosin) may have a potential therapeutic advantage.

Tamsulosin is considered the most pharmacologically uroselective of the commercially available agents because of its highest relative affinity for the alpha-1a receptor subtype. Recently, a new alpha-1a receptor selective blocker, silodosin (Rapaflo) was approved. It is indicated for treatment of the signs and symptoms of BPH.

The efficacy of the titratable alpha-blockers doxazosin and terazosin (Hytrin) is dose-dependent. Maximum tolerable doses have not been defined for any alpha-blocker; however, the higher the dose, the more likely the adverse events (orthostatic hypotension, dizziness, fatigue, ejaculatory disorder, nasal congestion).

An approximately 4- to 6-point improvement is expected in IPSS/AUA-SI scores when alpha-blockers are used. Interestingly, alpha-blocker therapy has not been shown to reduce the overall long-term risk of acute urinary retention (AUR) or BPH-related surgery.⁵

• Alpha-adrenergic receptor blockers
  • The alpha-blocking agents administered in BPH studies can be subgrouped according to receptor subtype selectivity and the duration of serum elimination half-lives.
  • Nonselective alpha-blockers include phenoxybenzamine.
  • Selective short-acting alpha-1 blockers include prazosin, alfuzosin, and indoramin.
  • Selective long-acting alpha-1 blockers include terazosin, doxazosin and slow-release (SR) alfuzosin.
  • Partially subtype (alpha-1a)–selective agents include tamsulosin and silodosin.
• Nonselective alpha-blockers
  • Phenoxybenzamine was the first alpha-blocker studied for BPH. Its nonselective nature causes it to antagonize both the alpha 1- and alpha 2-adrenergic receptors, resulting in a higher incidence of adverse effects.
  • Because of the availability of more alpha-1-receptor–specific agents, phenoxybenzamine is currently not often used for the treatment of BPH.
• Intraoperative floppy iris syndrome
  • Intraoperative floppy iris syndrome (IFIS) is characterized by miosis, iris billowing, and prolapse in patients undergoing cataract surgery who have taken or currently take alpha-1-blockers. It is particularly prevalent among patients taking tamsulosin. Patients on alpha-blocker therapy must disclose this to their ophthalmologists prior to cataract surgery so that the appropriate preventive measures can be taken.⁶
  • Bell et al reviewed exposure to alpha-adrenergic blockers frequently prescribed to treat BPH and their association with serious postoperative adverse effects following cataract surgery. The study included more than 96,000 older men who had undergone cataract surgery over a 5-year period (3.7% had recent exposure to tamsulosin and 7.7% had recent exposure to other alpha-blockers). Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43), specifically IFIS and its complications (ie, retinal detachment, lost lens or fragments, endophthalmitis). No significant associations were noted with exposure to other alpha-blocker medications (7.5% vs 8%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to tamsulosin or other alpha-blockers.⁷

Rationale for 5-alpha-reductase inhibitors in benign prostatic hyperplasia

Hormonal medical management emerged from the discovery of a congenital form of pseudohermaphroditism secondary to DHT deficiency (due to a lack of 5-alpha-reductase activity). This deficiency produced a hypoplastic prostate. The two types of 5-alpha-reductase include type 1 (predominantly located in extraprostatic tissues, such as skin and liver) and type 2 (predominant prostatic reductase).

Prostatic enlargement depends on the potent androgen DHT. In the prostate gland, type II 5-alpha-reductase metabolizes circulating testosterone into DHT (works locally, not systemically). DHT binds to androgen receptors in the cell nuclei; this can result in BPH. DHT promotes growth of prostatic tissue. Inhibition of 5-alpha-reductase type 2 blocks the conversion of testosterone to DHT, resulting in lower intraprostatic levels of DHT. This leads to inhibition of prostatic growth, apoptosis, and involution. The exact role of 5-alpha-reductase type 1 in normal and abnormal prostatic development is undefined. 5-Alpha-reductase inhibitors improve LUTS by decreasing prostate volumes; thus, patients with larger prostates may achieve a greater benefit. Further, maximal reduction in prostate volume requires 6 months of therapy.

• 5-Alpha reductase inhibitors
  • Finasteride (Proscar), a 4-aza-steroid, has demonstrated 5-alpha type II–blocking activity, resulting in the inhibition of DHT-receptor complex formation. This effect causes a profound decrease in the concentration of DHT intraprostatically, resulting in a consistent decrease in prostate size. One third of men treated with this agent exhibit improvements in urine flow and symptomatology.
  • Dutasteride (Avodart) has an affinity for both type 1 and type 2 5-alpha-reductase receptors. The significance of blockage of type 1 receptors is currently unknown.
  • Both finasteride and dutasteride actively reduce DHT levels by more than 80%, improve symptoms, reduce the incidence of urinary retention, and decrease the likelihood of surgery for BPH.
  • Adverse effects are primarily sexual in nature (decreased libido, erectile dysfunction, ejaculation disorder).
  • Both finasteride and dutasteride may reduce serum PSA values by as much as 50%. The decrease in PSA is typically maximally achieved when the maximal decrease in prostatic volume is noted (6 months). Thus, one must take this into account when using PSA to screen for prostate cancer.
  • Because these drugs interfere with the metabolism of testosterone, they are contraindicated in children and pregnant females. In addition, pregnant females or those who are considering conception should not handle crushed or broken tablets because of the potential for absorption and subsequent potential risk to a male fetus.
  • In patients with LUTS and enlarged prostates, 5-alpha-reductase inhibitors are believed to be appropriate and effective treatment.

Rationale for combination therapy with alpha-1-receptor blockade and 5-alpha-reductase inhibitors in benign prostatic hyperplasia

• The alpha-1-receptor blockers provide rapid relief, while the 5-alpha-reductase inhibitors target the underlying disease process.⁵ The Medical Therapy of Prostatic Symptoms (MTOPS) trial demonstrated that combination therapy reduced the risk of progression and showed a greater improvement in IPSS with combination therapy than with finasteride or doxazosin alone. The risks of AUR and BPH-related surgery were reduced with combination therapy or finasteride in comparison to doxazosin monotherapy.⁸
• The Symptom Management After Reducing Therapy (SMART-1) trial demonstrated that, after 6 months of combination therapy, discontinuation of the alpha-1-blocker is possible in men with moderate LUTS. However, those with severe LUTS may require longer combination therapy.⁸

Landmark clinical trials

Numerous phase II and phase III trials of drugs used in the treatment of BPH have been conducted. A few landmark studies are selected below.

• The Proscar Long-Term Efficacy and Safety Study (PLESS) evaluated clinical data of randomized controlled trials using alpha-adrenergic receptor blockers and/or 5-alpha-reductase inhibitors. This was a multicenter, 4-year, double-blind, placebo-controlled study of 3,040 men. Men with PSA levels of more than 10 ng/mL and those with prostate cancer were excluded. In the PLESS study, patients were randomized to receive placebo versus finasteride (5 mg/d) for 4 years. Results showed that patients treated with finasteride were at a significantly lower risk of developing AUR or needing surgery.⁹
• The Medical Therapy of Prostatic Symptoms (MTOPS) trial was a multicenter, 4- to 6-year, double-blind, randomized, placebo-controlled trial of 3,047 men with symptomatic BPH. The men were separated into 4 treatment groups to receive placebo, doxazosin, finasteride, or a combination of doxazosin and finasteride. Combination therapy was superior to placebo and monotherapy in reducing the risk of primary endpoints of the study (reduction in AUA-SI score, AUR, recurrent infections, renal insufficiency, incontinence, changes in flow, and PSA level and a lower rate of invasive treatments) and was well tolerated.¹⁰
• The Alfuzosin Long-Term Efficacy and Safety Study (ALTESS) was a double-blind, placebo-controlled study conducted to assess the impact of the alpha-1-blocker alfuzosin 10 mg daily on the risk of BPH/LUTS progression. This was a 2-year study of 1,522 men. Notably, this cohort of study patients consisted of men with greater risk factors for BPH progression (older age, higher IPSS scores, larger prostate size, lower Qmax, and higher PVR) than those in the MTOPS trial. Alfuzosin decreased the risk of LUTS deterioration and significantly improved QOL and peak flow urinary flow rate. Alfuzosin did not reduce the risk of AUR but tended to reduce the risk of surgery.¹¹
• The international real-life practice study of alfuzosin once daily (ALF-ONE) was a 3-year study conducted to assess the efficacy and safety of alfuzosin 10 mg once daily in 689 European men with a mean age of 67.6 years. The IPSS decreased by one third. There were significant improvements in nocturia and bother score. Clinical progression of worsening of IPSS (>4 points) was seen in 12.4%, AUR in 2.6%, and requirement of BPH-related surgery in 5.7%. Alfuzosin was well tolerated, with dizziness the most common adverse effect (4.5%). Notably, symptom worsening during treatment and high PSA levels appeared to be the best predictors of clinical progression.¹²
• The Combination of Avodart and Tamsulosin (CombAT) is an ongoing 4-year, multicenter, randomized, double-blind, parallel group study evaluating the safety and efficacy of dutasteride (dual 5-alpha-reductase inhibitor) and tamsulosin (alpha-1-blocker) separately and in combination. The cohort consists of 4,844 men aged 50 years or older with moderate-to-severe BPH symptoms (IPSS >12), prostate volume of 30 mL or greater, and a PSA level of 1.5-10 ng/mL. The two-year results revealed that combination therapy improved symptoms, urinary flow, and QOL better than monotherapy. The adverse-effect profile of combination therapy was similar to that of monotherapy (with either drug), although drug-related adverse events were more common with combination therapy.¹³

Phytotherapeutic agents and dietary supplements

• Phytotherapeutic agents and dietary supplements are considered emerging therapy by the AUA Guidelines panel and are not recommended for the treatment of BPH because of the lack of evidence at this time.
• Pharmaceuticals derived from plant extracts are widely used throughout the world for the treatment of various medical ailments. In 1998, Americans spent a total of $3.65 billion on all herbal remedies. In France and Germany, plant extracts have a market share of up to 50% of all drugs prescribed for symptomatic BPH. In the United States, these agents are also popular and readily available.
• The attraction to phytotherapeutic agents appears to be related to the perception of therapeutic healing powers of natural herbs, the ready availability, and the lack of adverse effects.
• Most of the phytotherapeutic agents used in the treatment of LUTS secondary to BPH are extracted from the roots, seeds, bark, or fruits of plants listed below. Some suggested active components include phytosterols, fatty acids, lectins, flavonoids, plant oils, and polysaccharides. Some preparations derive from a single plant; others contain extracts from 2 or more sources.
• Each agent has one or more proposed modes of action. The following modes of action are suggested:
  • Antiandrogenic effect
  • Antiestrogenic effect
  • Inhibition of 5-alpha-reductase
  • Blockage of alpha receptors
  • Antiedematous effect
  • Anti-inflammatory effect
  • Inhibition of prostatic cell proliferation
  • Interference with prostaglandin metabolism
  • Protection and strengthening of detrusor
• The origins of phytotherapeutic agents are as follows:
  • Saw palmetto, ie, American dwarf palm (Serenoa repens, Sabal serrulata) fruit
  • South African star grass (Hypoxis rooperi) roots
  • African plum tree (Pygeum africanum) bark
  • Stinging nettle (Urtica dioica) roots
  • Rye (Secale cereale) pollen
  • Pumpkin (Cucurbita pepo) seeds
• The mechanisms of action of some selected phytotherapeutic agents are as follows:
  • Saw palmetto (American dwarf palm): Extracts of the berries are the most popular botanical products for BPH. The active components are believed to be a mixture of fatty acids, phytosterols, and alcohols. The proposed mechanisms of action are antiandrogenic effects, 5-alpha-reductase inhibition, and anti-inflammatory effects. The recommended dosage is 160 mg orally twice daily. Studies show significant subjective improvement in symptomatology without objective improvements in urodynamic parameters. Minimal adverse effects include occasional GI discomfort.
  • African plum tree (P africanum): Suggested mechanisms of action include inhibition of fibroblast proliferation and anti-inflammatory and antiestrogenic effects. This extract is not well studied.
  • Rye (S cereale): This extract is made from pollen taken from rye plants growing in southern Sweden. Suggested mechanisms of action involve alpha-blockade, prostatic zinc level increase, and 5-alpha-reductase activity inhibition. Significant symptomatic improvement versus placebo has been reported.

Treatment of concomitant overactive bladder in men with benign prostatic hyperplasia

• Historically, anticholinergics were discouraged in men with BPH because of concerns of inducing urinary retention. Trials have demonstrated a slight increase in PVR; however, AUR rates were low. Importantly, these trials consisted of patients with low baseline PVR.
• Patients with symptomatic OAB not relieved with alpha-1-blockers may benefit from anticholinergic therapy. It is prudent to record the baseline PVR prior to initiation of anticholinergic therapy to assess for urinary retention.¹⁴

Treatment of concomitant erectile dysfunction in men with lower urinary tract symptoms/ benign prostatic hyperplasia

• It is recommended to first establish the alpha-1 blocker dose before treating the erectile dysfunction. The medication used to treat erectile dysfunction should be titrated to the lowest effective dose. Furthermore, sildenafil doses of greater than 25 mg should not be taken within 4 hours of any alpha-blocker.^15,16,17
• In addition, data suggest that sildenafil may improve mild-to-moderate LUTS. Nitric oxide may mediate relaxation of the prostatic urethra and/or bladder neck. The utility of phosphodiesterase inhibitors in the treatment of LUTS has yet to be defined.¹⁸

Surgical Care

• Transurethral resection of the prostate
  • TURP is considered the criterion standard for relieving BOO secondary to BPH. The indications for surgical intervention include AUR, failed voiding trials, recurrent gross hematuria, urinary tract infection, and renal insufficiency secondary to obstruction. Additional indications to proceed with a surgical intervention include failure of medical therapy, a desire to terminate medical therapy, and/or financial constraints associated with medical therapy. However, TURP carries a significant risk of morbidity (18%) and mortality risk (0.23%).
  • TURP is performed with regional or general anesthesia and involves the placement of a working sheath in the urethra through which a hand-held device with an attached wire loop is placed. High-energy electrical cutting current is run through the loop so that the loop can be used to shave away prostatic tissue. The entire device is usually attached to a video camera to provide vision for the surgeon.
  • Although TURP is often successful, it has significant drawbacks.
    • When prostatic tissue is cut away, significant bleeding may occur, possibly resulting in termination of the procedure, blood transfusion, and a prolonged hospital stay.
    • Irrigating fluid may also be absorbed in significant quantities through veins that are cut open, with possible serious sequelae termed transurethral resection syndrome (TUR syndrome). A urinary catheter must be left in place until the bleeding has mostly cleared.
    • The large working sheath combined with the use of electrical energy may also result in stricturing of the urethra.
    • The cutting of the prostate may also result in a partial resection of the urinary sphincteric mechanism, causing the muscle along the bladder outlet to become weak or incompetent. As a result, when the individual ejaculates, this sphincteric mechanism cannot keep the bladder adequately closed. The ejaculate consequently goes backwards into the bladder (ie, retrograde ejaculation), rather than from the end of the penis. Additionally, if the urinary sphincter is damaged, urinary incontinence may result.
    • TURP usually requires hospitalization.
    • The nerves associated with erection run along the outer rim of the prostate, and the high-energy current and/or heat generated by such may damage these nerves, resulting in impotence.
• Open prostatectomy
  • This procedure is now reserved for patients with very large prostates (>75 g), patients with concomitant bladder stones or bladder diverticula, and patients who cannot be positioned for transurethral surgery.
  • Open prostatectomy requires hospitalization and involves the use of general/regional anesthesia and a lower abdominal incision. The inner core of the prostate (adenoma), which represents the transition zone, is shelled out, thus leaving the peripheral zone behind. It may involve significant blood loss, resulting in transfusion. Open prostatectomy usually has an excellent outcome in terms of improvement of urinary flow and urinary symptoms.
  • More recently, laparoscopic simple prostatectomy has been performed at a number of institutions and appears to be feasible. However, prostatectomy performed in this fashion still appears to be associated with risk for significant blood loss. Experience to date with this procedure is limited.¹⁹
• Minimally invasive treatment for benign prostatic hyperplasia
  • There is considerable interest in the development of other therapies to decrease the amount of obstructing prostate tissue while avoiding the above-mentioned adverse effects associated with TURP. These therapies are collectively called minimally invasive therapies.
  • Most minimally invasive therapies rely on heat to destroy prostatic tissue; however, this heat is delivered in a limited and controlled fashion with the hope that the complications associated with TURP may be avoided. They also allow for the use of milder forms of anesthesia, which translates into less anesthetic risk for the patient.
  • Heat may be delivered in the form of laser energy, microwaves, radiofrequency energy, high-intensity ultrasound waves, and high-voltage electrical energy. Delivery devices are usually similarly passed through a working sheath placed in the urethra, although they are usually of a smaller size than that needed for TURP. Devices may also simply be attached or incorporated into a urinary catheter or passed through the rectum, from which the prostate may also be accessed.
  • Keep in mind that many of these minimally invasive therapies are undergoing constant improvements and refinements, resulting in increased efficacy and safety. Ask urologists about the specifics of the minimally invasive therapies that they use and what results they have experienced.
  • Transurethral incision of the prostate (TUIP) has been in use for many years and, for a long time, was the only alternative to TURP. It may be performed with local anesthesia and sedation.
    • TUIP is suitable for patients with small prostates and for patients unlikely to tolerate TURP well because of other medical conditions.
    • TUIP is associated with less bleeding and fluid absorption than TURP. It is also associated with a lower incidence of retrograde ejaculation and impotence than TURP.
  • Lasers deliver heat to the prostate in various ways. Lasers heat prostate tissue, causing tissue death by coagulative necrosis, with subsequent tissue contraction; however, laser coagulation of the prostate in this specific sense has met with limited results. Lasers have also been used to directly evaporate, or to melt away, prostate tissue, which is more effective than laser coagulation. Photoselective vaporization of the prostate produces a beam that does not directly come into contact with the prostate; rather, it delivers heat energy into the prostate, resulting in destruction/ablation of the prostate tissue. Potassium-titanyl-phosphate (KTP) and holmium lasers are used to cut and/or enucleate the prostate, similar to the TURP technique. These are widely used laser techniques.
    • Transurethral vaporization/ablation with the KTP or holmium laser can be performed with general or spinal anesthesia and can be performed in an outpatient setting. Catheter time usually lasts less than 24 hours. Recent studies suggest that photoselective vaporization of the prostate can significantly improve and sustain symptomatic and urodynamic outcomes. This procedure has been quite useful in patients who require anticoagulation (blood thinning) for various medical conditions, since anticoagulation does not need to be interrupted for this procedure, thus further decreasing patient risk.^20,21
    • Lasers may be used in a knifelike fashion to directly cut away prostate tissue (ie, holmium laser enucleation of the prostate), similar to a TURP procedure. The holmium laser allows for simultaneous cutting and coagulation, making it quite useful for prostate resection. Recent studies demonstrate that laser enucleation of the prostate is a safe and effective procedure for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay. TUR syndrome is not seen with this technique, because iso-osmotic saline is used for irrigation. Additionally, removed prostatic tissue is available for histologic evaluation, whereas vaporization/ablation technique does not provide tissue for evaluation. Holmium laser enucleation of the prostate may prove to be the new criterion standard for surgical management of BPH.^21,22
    • Laser treatment usually results in decreased bleeding, fluid absorption, length of hospital stay, and decreased incidence of impotence and retrograde ejaculation when compared with standard TURP. Additionally, because treating tissue with a laser involves a time interval during which dead cells slough and healing follows, patients may experience urinary urgency or irritation, resulting in frequent or uncomfortable urination for a few weeks.
    • The results of laser therapy vary from one another because not all wavelengths yield the same tissue effects. For example, interstitial lasers (eg, indigo lasers) are designed to heat tissue within the confines of the prostate gland and spread radiant energy at relatively low energy levels. They do not directly involve the urethral portion; thus, irritative symptoms following the procedure are potentially reduced. Contact lasers such as KTP or holmium, on the other hand, are designed to cut and vaporize at extremely high temperatures They usually bring about more relief of urinary symptoms than treatment with medicines, but not always as much as is provided with TURP. However, KTP laser vaporization and holmium laser enucleation yield results that rival those of TURP.
  • The use of microwave energy, termed transurethral microwave therapy (TUMT), delivers heat to the prostate via a urethral catheter or a transrectal route.
    • The surface closest to the probe (the rectal or urethral surface) is cooled to prevent injury. The heat causes cell death, with subsequent tissue contraction, thereby decreasing prostatic volume.
    • TUMT can be performed in the outpatient setting with local anesthesia.
    • Microwave treatment appears to be associated with significant prostatic swelling; a considerable number of patients require replacement of a urinary catheter until the swelling subsides. In terms of efficacy, TUMT places between medical therapy and TURP.
  • Transurethral needle ablation of the prostate (TUNA) involves using high-frequency radio waves to produce heat, resulting in a similar process of thermal injury to the prostate as previously described. A specially designed transurethral device with needles is used to deliver the energy.
    • TUNA can be performed under local anesthesia, allowing the patient to go home the same day.
    • Similar to microwave treatment, radiofrequency treatment is quite popular, and a number of urologists have experience with its use.
    • Radiofrequency treatment appears to reliably result in significant relief of symptoms and better urine flow, although not quite to the extent achieved with TURP.
  • High-intensity ultrasound energy therapy delivers heat to prostate tissue, with the subsequent process of thermal injury.
    • High-intensity ultrasound waves may be delivered rectally or extracorporeally and can be used with the patient on intravenous sedation.
    • Urinary retention appears to be common with its use.
    • High-intensity ultrasound energy also produces moderate results in terms of improvement of the urinary flow rate and urinary symptoms, although its use is now relatively limited compared to the more popular TUNA and TUMT.
    • High-intensity ultrasound is considered investigational at this time and should not be offered outside of clinical trials.
  • Mechanical approaches are used less commonly and are usually reserved for patients who cannot have a formal surgical procedure. Mechanical approaches do not involve the use of energy to treat the prostate.
    • Prostatic stents are flexible devices that can expand when put in place to improve the flow of urine past the prostate. Their use has been associated with encrustation, pain, incontinence, and overgrowth of tissue through the stent, possibly making their removal quite difficult. To date, their full role and long-term effects are not fully known.
    • Balloon dilation involves transurethral placement of a balloon, which is then inflated with the intent of expanding the prostatic urethra by "cracking" the prostatic capsule. Balloon dilation has largely been abandoned. Efficacy has not been demonstrated with this procedure.

Diet

Data from the Prostate Cancer Prevention Trial was evaluated for dietary risk factors for BPH. The data revealed that a diet low in fat and red meat and high in protein and vegetables may reduce the risk of symptomatic BPH. Additionally, regular alcohol consumption was associated with a reduced risk of symptomatic BPH, but this is to be interpreted cautiously given the untoward effects of excessive alcohol consumption.²³

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Alpha-adrenergic blockers

These agents block effects of postganglionic synapses at the smooth muscle and exocrine glands.

Phenoxybenzamine (Dibenzyline)

Nonselective alpha-adrenergic receptor blocker that antagonizes both alpha-1 and alpha-2 receptors. The nonselectivity leads to higher incidence of adverse effects, causing a decrease in use in clinical settings. Induces subjective improvement in urinary flow rates when compared to placebo. May improve daytime and nighttime urinary frequency. Improves symptoms in 75% of patients.

Prazosin (Minipress)

Treats prostatic hypertrophy. Improves urine flow rates by relaxing smooth muscle. Relaxation is produced by blocking alpha-1 adrenoreceptors in the bladder neck and prostate. Advantage over nonselective alpha-adrenergic blockers includes lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, clinical utility for BPH has been reduced. Improves urinary flow rate and frequency of micturition. Subjective improvement observed in 82% of patients treated. When increasing dosages, administer first dose of each increment at bedtime to reduce syncopal episodes. Although doses >20 mg/d do not usually increase efficacy, some patients may benefit from up to 40 mg/d.

Alfuzosin (UroXatral)

Alpha-1 blocker of adrenoreceptors in prostate. Blockade of adrenoreceptors may cause smooth muscles in bladder neck and prostate to relax, resulting in improvement in urine flow rate and reduction in symptoms of BPH.

Indoramin

Not available in the United States. Helps treat prostatic hypertrophy. Improves urine flow rates by relaxing smooth muscle. Relaxation produced by blocking alpha-1 adrenoreceptors in the bladder neck and prostate. Advantage over nonselective alpha-adrenergic blockers includes lower incidence of adverse effects. Because of availability of longer-acting, once-daily selective agents, clinical utility for BPH has been reduced. Improves urinary flow rate and frequency of micturition.

Terazosin (Hytrin)

Quinazoline compound that counteracts alpha1-induced adrenergic contractions of bladder neck, facilitating urinary flow in presence of BPH. Effect on voiding symptoms and flow rates is dose-dependent. Improves irritative and obstructive voiding symptoms. Improvement in flow rate is objective. Hytrin starter pack available for easy dosing progression to 5 mg.

Doxazosin (Cardura)

Inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decrease in total peripheral resistance and blood pressure. Long-acting alpha1-blocking agent with similar profile to terazosin. Improves irritative and obstructive voiding symptoms.

Tamsulosin (Flomax)

Alpha-adrenergic blocker specifically targeted to alpha-1 receptors. Has advantage of relatively less orthostatic hypotension and requires no gradual up-titration from initial introductory dosage. Inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decrease in total peripheral resistance and blood pressure. Improves irritative and obstructive voiding symptoms.

Silodosin (Rapaflo)

Selectively antagonizes postsynaptic alpha1-adrenergic receptors in prostate, bladder base, prostatic capsule, and prostatic urethra. This action induces smooth muscle relaxation and improves urine flow. Indicated for signs and symptoms of BPH.

5Alpha-reductase inhibitors

Inhibit the conversion of testosterone to DHT, causing DHT levels to drop, which, in turn, may decrease prostate size.

Finasteride (Proscar)

Inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. Beneficial in men with prostates >40 g. Improves symptoms and reduces prostatic size by 20-30%. Reduction in prostate size sustained 5 y following treatment. Improves urinary flow rate by 2 mL/s.

Dutasteride (Avodart)

Used to treat symptomatic BPH in men with an enlarged prostate. Improves symptoms, reduces urinary retention, and may decrease need for BPH-related surgery. Inhibits 5alpha-reductase isoenzymes types I and II. Suppresses >95% conversion of testosterone to DHT, causing serum DHT levels to decrease.

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