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Medical Management of BPH By Dr. Wissam Kh Kamal KAAUH Prostatic Zones 1-Anterior fibromuscular stroma 1/3 of prostate mass. Extends from bladder neck to sphincter. Replaced by adenoma. Continuous with capsule. Collagen, elastin, smooth and straited muscle. 2-Periphral Zone: Covers posterior and lateral gland. 70% of cancers arise here. Most common site of chronic prostatitis. 3- Central Zone: Ducts arise around opening of ejaculatory ducts. Glands distinct from rest of prostate. Expands in cone shape around ejaculatory ducts. Rare site of cancer arising. 4- Transition Zone Site of BPH development. Enlarges with age. Initial phase of BPH is formation of new glandular nodules. Second phase is increase in size of large nodules. 5- Periurethral Zone: Found proximal to the origin of the transition zone ducts. Confined within the preprostatic sphincter and course parallel to the axis of the urethra. Cross Section of The Prostate Vascular Supply Arterial supply from inferior vesical artery. Urethral branches are main blood supply to adenoma. Blood supply enters at bladder neck at 4 and 8 o’clock positions. Venous drainage through periprostatic plexus. Lymphatic drainage to obturator and internal iliac nodes. Nerve Supply Sympathetic and Parasympathetic innervations from pelvic plexus through cavernous nerves. Parasympathetic promotes glandular secretion. Sympathetic contraction of capsular and stromal smooth muscle. Location of the prostate Function of the Prostate The prostate gland is a male accessory sex gland. During ejaculation it produces alkaline prostatic fluid, which in combination with the products of the testes, seminal vesicles, urethral and bulbo-urethral glands, forms semen. BPH ETIOLOGY AND PATHOPHYSIOLOGY BPH is a common cause of the LUTS in aging men. Histopathologically, BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. The observed increase in cell number may be due to epithelial and stromal proliferation or to impaired programmed cell death leading to cellular accumulation. Androgens, estrogens, stromal-epithelial interactions, growth factors, and neurotransmitters may play a role, either singly or in combination, in the etiology of the hyperplastic process. Although androgens and growth factors stimulate cell proliferation in experimental models, the relative role of cell proliferation in human BPH is questioned because there is no clear evidence of an active proliferative process. Although it is possible that the early phases of BPH are associated with a rapid proliferation of cells, the established disease appears to be maintained in the presence of an equal or reduced rate of cell replication. Androgens not only are required for normal cell proliferation and differentiation in the prostate but also actively inhibit cell death. The Role of Androgen Although androgens do not cause BPH, the development of BPH requires the presence of testicular androgens during prostate development, puberty, and aging . Patients castrated prior to puberty or who are affected by a variety of genetic diseases that impair androgen action or production do not develop BPH. It is also known that prostatic levels of dihydrotestosterone (DHT) as well as the androgen receptor (AR) remain high with aging despite the fact that peripheral levels of testosterone are decreasing. In the prostate the nuclear membrane bound enzyme steroid 5α-reductase converts the hormone testosterone into DHT, the principal androgen in this tissue. Ninety percent of total prostatic androgen is in the form of DHT, principally derived from testicular androgens. Adrenal androgens may constitute 10% of total prostatic androgen, although the importance of this stored hormone source in the etiology of BPH is negligible. Despite the importance of androgens in normal prostatic development and secretory physiology, there is no evidence that either testosterone or DHT serves as the direct mitogen for growth of the prostate in older men. Androgen Receptors The prostate, unlike other androgen-dependent organs, maintains its ability to respond to androgens throughout life. In fact, there is evidence to suggest that nuclear AR levels may be higher in hyperplastic tissue than in normal controls. Age-related increases in estrogen, as well as other factors, may increase AR expression in the aging prostate, leading to further growth (or to a decrease in cell death), despite decreasing levels of androgen in the peripheral circulation and “normal” levels of DHT in the prostate. 5 Alpha-reductase Enzymes Two steroid 5α-reductase enzymes have been discovered, each encoded by a separate gene. Type 1 5α-reductase, the predominant enzyme in extraprostatic tissues, such as skin and liver, is inhibited by dutasteride but not substantially by finasteride. Type 2 5α-reductase is the predominant prostatic 5α-reductase, although it is also expressed in extraprostatic tissues. It is mainly sensitive to inhibition by finasteride and dutasteride. Tissues in which type I and type II 5reductase are predominant Type I Type II Skin (sebaceous glands) Hair follicles Liver Seminal vesicles Liver Prostate gland Adrenal glands Epididymis Internal/external genital tissues Slide III.4 Clearly, the type 2 enzyme is critical to normal development of the prostate and hyperplastic growth later in life. The role of type 1 5α-reductase in normal and abnormal prostate growth remains to be defined. Given that finasteride produces prostate size reduction identical to that with dual type1/type 2 inhibitors and roughly equivalent to that with castration, it is unlikely that type 1–derived DHT is critical to hyperplastic growth. Immunohistochemical studies with type 2 5α-reductase specific antibodies show primarily stromal cell localization of the enzyme. Data demonstrates that the stromal cell plays a central role in androgendependent prostatic growth and that the type 2 5α-reductase enzyme within the stromal cell is the key androgenic amplification step. The Role of Estrogen the role of estrogens in the development of human BPH is not clear. Serum estrogen levels increase in men with age. There is also suggestive evidence that intraprostatic levels of estrogen are increased in men with BPH. Patients with larger volumes of BPH tend to have higher levels of estradiol in the peripheral circulation. Although there are relatively low concentrations of classical high-affinity estrogen receptors in human BPH there may be a sufficient amount for biologic activity. At present, the role of estrogens in human BPH is not as firmly established as the role of androgens. Regulation of Programmed Cell Death Androgens (presumably testosterone and DHT) appear to suppress programmed cell death elsewhere in the gland. Following castration, active cell death is increased in the luminal epithelial population as well as in the distal region of each duct. Abnormal hyperplastic growth patterns, such as BPH, might be induced by local growth factor or growth factor receptor abnormalities, leading to increased proliferation or decreased levels of programmed cell death. Growth factors and prostate development A number of growth factors expressed by mesenchymal or epithelial components of the prostate have been identified: – stimulatory growth factors: epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF) and transforming growth factor a (TGF-a) – inhibitory growth factors including transforming growth factor b (TGF-b) Growth factors and prostate development A number of polypeptide growth factors and receptors are subject to androgenic influence due to DHT/RA–DNA interactions This can alter the balance of cell proliferation and death to tip the balance in favour of decreased proliferation and apoptosis Removal of androgens results in decreased expression of stimulatory factors and increased expression of inhibitory factors The interplay of the growth factors may ultimately determine the amount of stromal and glandular hyperplasia in BPH Other Etiological Factors Inflammation, common in BPH specimens, may play a role in the pathogenesis of the disease through cytokines that promote cell growth or lead to smooth muscle contraction. BPH can have a familial inheritance, especially if large prostate volumes and surgical intervention at a young age are seen in the pedigree. Epidemiology and natural Hx There is no globally accepted epidemiologic definition of BPH, and, thus, prevalence and incidence rates must be viewed in the context of the definitions chosen by the investigator reporting the data. Despite the significantly different proportion of men admitting to moderate to severe symptoms, a clear trend toward an increase in symptom scores with advancing age is noticeable in all reported studies. In general, in all cross-sectional studies prostate volume as assessed by TRUS has been found to increase slowly but steadily with advancing age. Analytic epidemiologic data suggest a limited role of classical determinants of the disease such as religion, socioeconomic factors, sexual activity, alcohol intake, hypertension, dietary factors, and others. There is conflicting evidence regarding smoking and some evidence suggesting dietary factors, obesity, and increased BMI as determinants of disease severity. Pathophysiology Prostate volume static Muscle tonus Obstruction dynamic Pathophysiology of BPH – A static component (mechanical compression of the urethra by the enlarged prostate gland) –A dynamic component (increased tone of smooth muscle fibres in the bladder neck and prostate gland) – Together, the two components can give rise to a variety of lower urinary tract symptoms (LUTS) The pathophysiology of BPH is complex . Prostatic hyperplasia increases urethral resistance, resulting in compensatory changes in bladder function. However, the elevated detrusor pressure required to maintain urinary flow in the presence of increased outflow resistance occurs at the expense of normal bladder storage function. Obstruction-induced changes in detrusor function, compounded by age-related changes in both bladder and nervous system function, lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints. Definition of BPH: Histologically: is a microscopic diagnosis characterized by cellular proliferation of the stromal and epithelial elements of the prostate. Radiologically: enlarged prostate either on ultrasound or with three-dimensional diagnostic imaging studies of the male pelvis. Urodynamically: a synchronous observation of elevated voiding pressure and a low urinary flow rate in the absence of other disease processes that cause bladder outlet obstruction. Clinically:a constellation of signs and lower urinary tract symptoms (LUTS) that develop in the male population in association with aging and prostatic enlargement presumably caused by BOO. BPH appearance A characteristic of the gross appearance of BPH is rubbery yellow/grey nodules of variable size within the prostate gland. The nodules are composed of epithelium, smooth muscle and fibrous tissue in varying amounts, which can be further classified. BPH 5/25/2017 Kristen G. Barbee, RN, BSN 41 Diagnosis The complex of symptoms now commonly referred to as LUTS is not specific for BPH Aging men with a variety of lower urinary tract pathologic processes may exhibit similar, if not identical, symptoms. Voiding and Storage Symptoms Associated with Clinical BPH Bladder Outlet Obstruction Prostatic Enlargement Impaired Detrusor Contractility Involuntary Bladder Contractions Voiding Symptoms: Storage Symptoms: •Hesitancy •Weak Stream •Intermittency •Straining •Prolonged Voiding •Sense of incomplete emptying •Decreased flow rates •Urgency •Frequency •Nocturia •Urge incontinence •Pain •Decreased bladder capacity (Small voided volume) Post -void symptoms: •Postvoid dribble or terminal dribble •Post-void residual urine Complications of BPH = Absolute Indications for Surgery Rec. UTI Rec. hematuria Retention of urine Bladder stones Bladder diverticulum Bilateral Hydronephrosis & Renal insufficiency VUR Anatomical hernias 5/25/2017 Kristen G. Barbee, RN, BSN 45 Evaluation History. Physical examination. Investigations. Symptom assessment. History A detailed medical history should be taken to identify other causes of voiding dysfunction or cormorbidities that may complicate treatment . Specific additional areas to discuss when taking the history of a man with BPH symptoms include a history of hematuria, UTI, diabetes, nervous system disease (e.g., Parkinson's disease or stroke), urethral stricture disease, urinary retention, and aggravation of symptoms by cold or sinus medication. AUA Symptom Score Sheet Not at all Less than 1 time in 5 Less than half the time About half the time More than half the time Almost always 0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5 None 1 time 2 times 3 times 4 times 5 times or more 0 1 2 3 4 5 Your score Incomplete emptying Over the past month, how often have you had a sensation of not emptying your bladder completely after you finish urinating? Frequency Over the past month, how often have you had to urinate again less than two hours after you finished urinating? Intermittency Over the past month, how often have you found you stopped and started again several times when you urinated? Urgency Over the last month, how difficult have you found it to postpone urination? Weak stream Over the past month, how often have you had a weak urinary stream? Straining Over the past month, how often have you had to push or strain to begin urination? Your score Nocturia Over the past month, many times did you most typically get up to urinate from the time you went to bed until the time you got up in the morning? Quality of life due to urinary symptoms If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that? Delighted Pleased Mostly satisfied Mixed – about equally satisfied and dissatisfied Mostly dissatisfied Unhappy Terrible 0 1 2 3 4 5 6 Total score: 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. D.D Of BPH BPH Urethral Stricture Neurogenic Bladder Prostatitis CaP Physical Examination A DRE and a focused neurologic examination should usually be performed. In addition, examination of the external genitalia is indicated to exclude meatal stenosis or a palpable urethral mass, and an abdominal examination is necessary to exclude an overdistended, palpable bladder. The DRE and focused neurologic examination are done to detect prostate or rectal malignancy, to evaluate anal sphincter tone, and to rule out any neurologic problems that may cause the presenting symptoms. The presence of induration is as important finding as the presence of a nodule and should be correlated with a serum PSA value so that the need for prostatic biopsy can be assessed. DRE DRE establishes the approximate size of the prostate gland. estimation of prostate size is important to select the most appropriate pharmacologic or technical approach. DRE provides a sufficiently accurate measurement in most cases. However, the size of the prostate is not critical in deciding whether active treatment is required. Investigations Urinalysis: a urinalysis should be done to rule out UTI and hematuria. Serum Creatinine Measurement: the recently published AUA guidelines on BPH no longer recommend routine creatinine measurement in the standard patient. Serum Prostate-Specific Antigen: Prostate cancer can lead to LUTS by producing bladder outflow obstruction similar to BPH. Moreover, prostate cancer commonly coexists with BPH. Additional Diagnostic Tests Additional testing should be considered after the initial evaluation if there is a significant chance the patient's LUTS may not be due to BPH. patients with a normal initial evaluation and only mild symptomatology on the IPSS (scores 0 to 7) do not need additional diagnostic evaluation. Urinary flow rate, postvoid residual (PVR) urine, and pressure-flow urodynamic studies are appropriate tests to consider in the evaluation of men with moderate to severe symptoms (IPSS ≥ 8). Uroflowmetry The flowmeter device measures the quantity of fluid passed per unit time In addition, several different values can be calculated – voided volume: the total amount of urine voided – max flow rate (Qmax): the fastest rate at which urination occurs – average flow rate = voided volume/flow time – time to maximum flow: time between the onset of micturation and when peak flow occurs – flow time: the time over which measurable urine flow occurs Uroflowmetry Qmax is the most useful uroflow measure used and provides a good indication of whether a patient is obstructed or not Patients with a value: – <10 ml/sec are generally considered obstructed – >15 ml/sec are judged unobstructed – in the range of 10–15 ml/sec are equivocal Accuracy is improved if the voided volume exceeds 150 ml Uroflowmetry Unobstructed Detrusor underactivity Obstructed Urethral stricture Post-void residual urine volume (PVRV) PVRV measurement is performed noninvasively using transabdominal ultrasound It can be useful in assisting with treatment decisions but should not be used alone to diagnose BPH Patients found to have a large PVRV should receive active treatment, otherwise they may be more likely to develop AUR or fail conservative therapy Post-void residual urine volume (PVRV) PVRV measurement can also be useful for monitoring improvement or worsening of BPH in non-treated patients Although an increased PVRV may be indicative of obstruction, more than one measurement should be made because variation has been known to occur between voids Urodynamics These are the only means by which outflow obstruction can be diagnosed It is expensive and invasive, involving the introduction of a small catheter, either urethrally or suprapublically, to measure detrusor pressure within the bladder (generated by the contracting bladder muscle minus rectal pressure) It can can be used to distinguish outflow obstruction from impaired detrusor contractility It has been suggested that this technique should be confined to patients for whom surgery to relieve obstruction is being considered Cystoscopy Cystoscopy is not recommended to determine the need for treatment . The test is recommended for men with LUTS who have a history of microscopic or gross hematuria, urethral stricture disease (or risk factors such as history of urethritis or urethral injury), bladder cancer or suspicion of carcinoma-in-situ, or prior lower urinary tract surgery (especially prior TURP). Cystoscopy may be considered in men with moderate to severe symptoms who have chosen (or require) surgical or other invasive therapy to help the surgeon determine the most appropriate technical approach. It provides visual documentation of the appearance of the prostatic urethra and bladder in men with BPH. Potential benefits of cystoscopy include : the ability to demonstrate prostatic enlargement and visual obstruction of the urethra and the bladder neck. identification of specific anatomic abnormalities that alter clinical decision making. identification of bladder stones, trabeculation, and diverticula. measurement of PVR; and the ruling out of unrelated bladder and urethral pathologic processes. Imaging of the Urinary Tract Upper urinary tract imaging is not recommended in the routine evaluation of men with LUTS unless they also have one or more of the following: hematuria, UTI, renal insufficiency (ultrasound recommended), history of urolithiasis, or history of urinary tract surgery . Of all renal imaging studies performed in men with BPH, 70% to 75% are entirely normal. Only a small fraction of the 25% to 30% of abnormal findings mandate changes in the management of the patient. Management Of BPH Management of Patients With Mild Symptoms or Moderate to Severe Symptoms Without Bother Patients with mild symptoms of BPH (AUA Symptom Score <7) and patients with moderate or severe symptoms (AUA Symptom Score > 8) who are not bothered by their symptoms (i.e., they do not interfere with the daily activities of living) should be managed using a strategy of watchful waiting. Management of Patients With Bothersome Moderate to Severe Symptoms Treatment options for patients with bothersome moderate to severe symptoms of BPH (AUA Symptom Score > 8) include watchful waiting and the medical, minimally invasive, or surgical therapies. Information on the benefits and harms of the BPH treatment options (including watchful waiting) should be explained to patients with moderate to severe symptoms (AUA Symptom Score > 8) who are bothered enough to consider therapy. Treatment options for patients with moderateto severe symptoms of benign prostatic hyperplasia Watchful Waiting Medical Therapies Alpha-adrenergic blockers Alfuzosin Doxazosin Tamsulosin Terazosin 5 Alpha-reductase inhibitors Dutasteride* Finasteride Combination therapy (alpha blocker and 5 alphareductaseinhibitor). Minimally Invasive Therapies Transurethral microwave heat treatments CoreTherm™* Prostatron® (various versions) Targis® TherMatrx™* Transurethral needle ablation UroLume® stent‡ Surgical Therapies Transurethral resection of the prostate Transurethral electrovaporization Transurethral incision of the prostate Transurethral holmium laser resection/enucleation Transurethral laser vaporization Transurethral laser coagulation (e.g., visual laser ablation) Open prostatectomy Watchful Waiting A significant proportion of men with LUTS will not elect medical or surgical intervention because the symptoms are not bothersome. The complications of treatment are perceived to be greater than the inconvenience of the symptoms, and there is a reluctance to take a daily pill owing to either side effects and the cost of treatment. Reassured that the symptoms are not caused by cancer or other serious genitourinary pathology, or that the delay in treatment will not have irreversible consequences, watchful waiting is often the patientdriven treatment of choice in the absence of absolute indications for intervention. Watchful Waiting – Periodic monitoring – Symptoms – DRE – Flow-rate – PSA – U.S (PVRV) Medical Therapy The medical therapies for BPH are alpha-adrenergic blockers, 5alpha-reductase inhibitors, combination therapies, and phytotherapy (use of plant extracts). Medical therapies are not as efficacious as surgical therapies but may provide adequate symptom relief with fewer and less serious associated adverse events. Alpha-adrenergic blocker therapy Alfuzosin, doxazosin, tamsulosin and terazosin are appropriate treatment options for patients with LUTS secondary to BPH. Although there are slight differences in the adverseevent profiles of these agents, it’s believed that all four agents have equal clinical effectiveness. Four long-acting alpha-1-antagonists, terazosin, doxazosin, tamsulosin, and alfuzosin have been approved by the Food and Drug Administration in the United States for treatment of the symptoms of BPH. Prazosin, a short-acting alpha-1-antagonist, is occasionally used for BPH, but the other medications are preferred. Alpha-blocker therapy is based on the hypothesis that clinical BPH is partly caused by alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction. Alpha-adrenergic receptor antagonists (blockers) such as doxazosin,tamsulosin, alfuzosin, and terazosin inhibit this process and thus relieve the bladder outlet obstruction. Side effects of Alpha-adrenergic blocking agents Postural hypotension. Blurred vision. Dry mouth. Nasal Congestion. Drowsiness. Ejaculation failure. Alpha-adrenergic blocking agents ■ Agents requiring dose titration: Doxazosin ( Cardura) 1 & 4 mg tablets, maintenance dose 2 mg OD Titrates upwards over several weeks. Terazosin ( Hytrin) 1mg slowly increase up to 20mg /day ■ Agents not requiring dose titration Alfuzosin ( Xatral) 10 mg XL OD Tamsulosin ( Omnic) 0.4mg main problem abnormal ejaculation May increased to 0.8 mg after 2-4 wks These drugs differed in their side-effect profiles. The frequency of side effects with alfuzosin and tamsulosin bothersome enough to cause withdrawal from studies was similar to placebo (4 to 10 percent) but was 4 to 10 percent higher in men treated with terazosin and doxazosin. The most important side effects were orthostatic hypotension and dizziness. Terazosin and doxazosin generally need to be initiated at bedtime (to reduce postural lightheadedness soon after starting the medication) and the dose should be titrated up over several weeks. Tamsulosin and alfuzosin have less effect on blood pressure than either terazosin or doxazosin, and tamsulosin may further have slightly less effect on blood pressure than alfuzosin. These differential effects on blood pressure by different alpha-1antagonists may be due to their differential blocking of alpha-1-receptor subtypes. 5-Alpha-reductase inhibitors There are two 5-alpha-reductase inhibitors, finasteride and dutasteride. These drugs act by reducing the size of the prostate gland. Treatment for 6 to 12 months is generally needed before prostate size is sufficiently reduced to improve symptoms. Patients with symptomatic prostatic enlargement but without signs of bother may be offered a 5 alphareductase inhibitor to prevent progression of the disease. The efficacy of finasteride appears to persist with long-term treatment. As an example, a trial of over 3000 men who were treated daily with 5 mg of finasteride or placebo demonstrated that the improvements in symptom scores, maximal urinary flow rates, and prostate volume were maintained for more than four years. The most important findings were that finasteride treatment decreased the probability of surgery and acute urinary retention. A 5 alpha-reductase inhibitor is the sole hormonal therapy, to date, that demonstrates both efficacy and acceptable safety for treatment of BPH. Finasteride can reduce the size of the prostate, can increase peak urinary flow rate, and can reduce BPH symptoms. The Panel's evidence-based review determined that a 5 alpha-reductase inhibitor is effective in partially relieving symptoms but is less effective for this purpose than alphablocker therapy. It lowers serum and intraprostatic dihydrotestosterone, but not to castration levels. It lowers serum PSA, butdoes not mask the PSA-based detection of prostate cancer. In general, patients will perceive this level of symptom improvement as a meaningful change. Finasteride is ineffective in patients who do not have enlarged prostates. Reported adverse events are primarily sexually related and include: 1. decreased libido. 2. ejaculatory dysfunction. 3. erectile dysfunction and are reversible and uncommon after the first year of therapy. Combination Therapy The Medical Therapy of Prostatic Symptoms (MTOPS) trial, a prospective, randomized, double-blind, multicenter, placebo-controlled trial, was established to determine whether medical therapy can prevent or delay the progression of BPH in the long term. In 18 academic centers across the United States a total of 3047 patients were recruited and randomized to receive doxazosin, finasteride, a combination of both, or placebo. Disease progression was defined as a worsening of BPH symptoms according to the AUA symptom index (AUASI). Progression was deemed to have occurred in the case of one of the following: - A 4-point rise in AUASI, confirmed by a second visit within 4 weeks; - A 50% increase in creatinine relative to baseline levels. - AUR. - Two or more UTIs within 1 year or a single episode of urosepsis due to BOO. - Socially unacceptable incontinence. The results of the trial suggest that the combination of doxazosin and finasteride exerts a clinically relevant, positive effect on rates of disease progression (McConnell et al, 2003). Men who received combination therapy were significantly less likely to experience BPH progression than those receiving either monotherapy or placebo, with risk reduction rates of 39% for doxazosin, 34% for finasteride, and 67% for combination therapy compared with placebo. Invasive therapy and AUR risk were significantly reduced by finasteride and combination therapy. AUA symptom score and Qmax improved significantly more in the combination therapy group compared with the monotherapy groups, whereas adverse events were similar to previously reported studies. In addition to indicating the potential benefits of combination therapy, MTOPS provided important data regarding the natural history of untreated BPH and the prediction of BPH patients who will respond most effectively to medical treatment: Although the patients receiving finasteride alone or in combination experienced the expected decrease in prostate volume, patients on placebo or doxazosin alone experienced an increase in prostate volume from a baseline of 34.0 mL by 9.3 (30.3%) (placebo) and from 36.4 mL by 9.9 (31.4%) (doxazosin), respectively. Conclusion The combination of an alpha-adrenergic receptor blocker and a 5-alpha-reductase inhibitor (combination therapy) is an appropriate and effective treatment for patients with LUTS associated with demonstrable prostatic enlargement. Phytotherapy Herbal therapies for BPH are commonly used in Europe; these remedies comprised 70 percent of spending for drug treatment of prostatism in Germany in 1997. Saw palmetto is approved by the German Commission E for stage I and II (mild to moderate) BPH. Two herbal extracts have officially been approved for the treatment of prostatism in France. No herbal therapies have been approved by the United States Food and Drug Administration for this purpose, although many men probably try these treatments. Phytotherapy Most phytotherapeutic preparations are plant extracts with different components manufactured by different extraction procedures, which prevents comparison of the preparations. Although numerous in-vitro experiments have been conducted to determine their possible mechanisms of pharmaceutical action, it is uncertain which of the actions demonstrated in vitro might be responsible for clinical responses in vivo. Appropriate randomized placebo-controlled clinical trials monitored by an outside agency are needed to ascertain and to confirm the efficacy of these products. Dr. Wissam Kh. Kamal R2 Urology KAUH