Philippine Urological Association, Inc.

Transcription

1 Philippine Urological Association, Inc. 3/F, Philippine College of Surgeons Bidg., 992 EDSA, Quezon City TeleFax No.: Executive Committee and Board Members 1997 President Vice President Secretary Treasurer Board Members Eduardo R. Gatchalian, M.D. Ernesto V. Arada III, M.D. Antonio L. Anastacio, M.D. Lester A. Garcia, M.D. Jesus Benjamin L. Mendoza/M.D. Telesforo E. Gana, Jr., M.D. Nelson A. Patron, M.D.

2 benign prostatic hyperplasia Abelardo M. Prodigalidad, M.D. Prostate Health Committee Chairman

3 Algorithm for the Initial Evaluation of Patients with Prostatism 1 2 Signs/ Symptoms of Prostatism Male 50 yrs. old or older Urologic History 3 Gross or Microscopic Hematuria, Recurrent UTI, Retention, Bone Pain present? 4 N Physical Examinations Abdominal Examination DRE (Digital Rectal Examination 5 Distended bladder/malignant prostated? 6 N 7 Are the following laboratory tests positive?* Refer to Urologist 8 N 9 Initial Evaluation Consistent with BPH IPSS (International Prostate Symptom Score) See Figure 2 Figure 1 * Laboratory Tests: Urinalysis > (+) RBC, WBC, Protein PSA (Prostate Specific Antigen > elevated values Urine flow rate > <10 ml/sec Residual Urine by Ultrasound > >200 ml Renal Function Tests > elevated BUN and Creatinine 385

4 Management After Initial Evaluation Consistent with BPH 1 Assessment of Symptoms (IPSS) 2 Mild Symptoms Score IPSS 0-7 FR >15 ml/sec R.U. = <50 ml? 4 N Moderate Symptoms Score IPSS 8-19 FR ml/sec R.U. <200 ml? N Watchful Waiting (Wawa Bothersomeness 6 Mainly Irritative Symptoms plus Small Prostate? N Mainly Obstructive Symptoms plus Large Prostate? 7 9 Alpha Adrenergic Blockers Terazosin Alfuzocin Doxazosin Volume Reducers Finasteride Mepartricin Phytotherapy Responsive to Treatment Continue Treatment 13 Severe Symptoms Score IPSS FR - <10 ml/sec. R.U. >200 ml 12 N Non Responders After Adequate Duration or Interim Changes in Digital Rectal Exam (DRE) & Prostate Specific Antigen (PSA) 14 Refer to Urologists for Surgery Figure 2 387

5 Guidelines in the Diagnosis and Treatment of Benign Prostatic Hyperplasia: (The Enlarged Prostate) Introduction Up until the late 1980s, patients with symptomatic BPH had very limited therapeutic options so that patients with severe symptoms were surgically treated and those with mild to moderate symptoms were observed until their symptoms worsen. Before the advent of medical treatment about 80% of all men with this diagnosis eventually underwent TURP. This last decade witnessed a tremendous progress in the diagnosis and treatment of BPH that included a better understanding of the patho-physiology in BPH, discoveries of pharmacologic agents, development of technological devices for minimally invasive procedures and refinements in the techniques and instruments used for the surgical treatment of BPH. At present, a spectrum of treatment modalities exists for patients with symptomatic BPH extending from watchful waiting to open surgery. In the middle of this spectrum are the minimally invasive procedures and medical treatment. The traditional practice of surgical intervention by the Urologists is no longer tenable but is gradually being replaced by the minimally invasive procedures and pharmacological agents, mostly the latter. This spectrum allows the Urologists (and the generalists) to adopt a treatment modality suited to the needs of the individual patients, taking into consideration the efficacy and adverse effects of a particular modality, the retreatment rate and cost of treatment. Likewise, patients can now participate in the decision making and greatly influence the choice of treatment options. Lastly, the general practitioners are now heavily involved in the treatment of BPH. They are tasked to provide an accurate diagnosis of BPH, have adequate knowledge of the different treatment modalities, in particular, the different available pharmacologic agents, their side effects and also identify that group of patients with BPH who may require outright referral to Urologists for workup and possible surgery (Figure 1 - Appendix). Definition The Enlarged Prostate : Benign Prostatic Hyperplasia (BPH) BPH is the most common benign tumor in elderly male and, is pathologically defined as the formation of benign nodules in the transition zone and periurethral tissues of the prostate resulting from cellular proliferation that may lead to an increase in prostate size. Initially, these nodules are small but enlarge and coalesce over time to produce obstruction of the prostatic urethra and cause symptoms later in life. This constellation of signs and symptoms of obstruction and irritation are collectively referred to as Prostatism (Clinical BPH) (Table I -Appendix). Signs & Symptoms The elements responsible in the production of these symptoms are due to mechanical and dynamic factors. The mechanical factors relate to the growth and intraurethral intrusion of the prostatic lobes which are dependent on prostate size. The weakened urinary bladder wall contractility (decompensation) contributes to the mechanical factors. Dynamic factors refer mainly to the contraction, spasticity and rigidity of the bladder neck, prostatic urethra, trigone and bladder wall resulting from stimulation mediated through the alphaadrenergic receptors which are abundantly distributed in these areas. Benign prostatic hyperplasia is responsible for urinary symptoms in the majority of men over 50 years old. Random autopsy findings reveal that 40% of men in their 50's and 90% in their 80's have microscopic evidence of the disease. Half of men over 80 years old with grossly detectable (macroscopic) tumor will develop symptoms. Diagnosis Diagnosis of BPH: Case-Finding of BPH Many patients have bothersome symptoms of BPH but do not seek professional help for fear of the discovery of cancer, the eventuality of surgery and the false belief that symptoms are part of the ageing process or that frequency reflects good functioning kidneys and urinary tract. Oftentimes patients develop urinary retention following surgery like cataract extraction or hernia repair, simply because they failed to volunteer their urinary symptoms prior to surgery or when consulting a physician for unrelated illnesses. Therefore, case finding of BPH must be considered in males over 50 years old who visit the clinic for any reason. The process begins by asking three simple questions. Do you get up at night to urinate? Are you bothered by your urination habits? Is your urine flow decreased at all? Any two affirmative answers to these questions warrants further investigation and in its consensus workshop, the Prostate Health Committee of the Philippine Urological Association, Inc. considers the following steps manda- 389

6 tory in the initial evaluation of patient with BPH: (Figure 2 - Appendix). Initial Evaluation Mandatory Procedures in the Initial Evaluation of Patients with BPH (See Figure 2 - Appendix) Complete medical history with emphasis on the urinary signs and symptoms may identify other possible causes or differential diagnosis of the voiding dysfunctions, and other co-morbidities that may or may not be related lo BPH Prescription medicines that affect urination must be identified Do general physical and abdominal and neurologic examination thoroughly to discover abnormalities that may or may not be related to BPH such as distended bladder, enlarged kidneys and abnormal neurologic findings (Figure 3 - Appendix). Do Digital Rectal Examination (DRE). This examination is of paramount importance in the diagnosis of prostate disorder. Basically, it allows the physician to determine the consistency, size, shape, mobility, tenderness of the prostate. It also allows assessment of the anal sphincter activity, anal lesions and others. A normal prostate is smooth, elastic and non-tender while a doughy and tender prostate suggests an inflammatory condition. BPH presents as a smooth, rubbery, non-tender prostate while in cancer the prostate is from firm to hard; smooth to nodular in character. Any suspicion of prostatic malignancy requires biopsy preferably by a Urologist. Consistency is the most important parameter for general practitioner. The size is difficult to assess and does not correlate with the degree of symptoms. Mandatory laboratory tests includes urinalysis that will identify hematuria, pyuria, proteinuria or other significant findings suggestive of complicated BPH or other kidney disorders. Renal Function Tests - Determination of serum Creatinine and Urea nitrogen is extremely important because 10% of BPH patients are azotemic. Serum PSA determination Prostate Specific Antigen (PSA) This is a glycoprotein that is secreted by the epithelial cells of the prostate whose function is to liquify the semen after ejaculation. It can be detected in the serum in increased levels in any disease of the prostate (cancer, infection, BPH) and other conditions like urinary tract infection, urinary retention, after urethral instrumentation or ejaculation. The normal value is 0-4 ng./ml but other methods of assay such as the 3rd generation assay have a different normal range. It is recommended that a 390 CPM 1 ST EDITION check with the laboratory where the test is done be made if the report does not indicate the normal range. It varies with age and prostate volume (Table 2 - Appendix). The significance of determining the PSA in the initial evaluation of patient with BPH is identifying the risk of that patient harboring cancer of the prostate (Table 3 - Appendix). It is not utilized to diagnose cancer of the prostate. When used as a monitoring device, it is important for the practitioners to remember that some drugs or agents particularly the anti-androgens including finasteride will influence the value or level of PSA. Finasteride reduces the value by 50% after 3 to 6 months of treatment. Another aspect of PSA that is important is the so-called PSA velocity. It is the rate of increase in the level of PSA in one year which should NOT be more than 20% from the baseline value. Any increase of more than 20% should arouse suspicion of cancer of the prostate and evaluation towards this direction is necessary. Urine Flow Rate Urine flow rate determination is not mandatory but a recommended test that is important when significant outflow track obstruction is suspected (Table 4 - Appendix). It is easily and non-invasively performed with the use of a uroflowmeter in the urodynamic laboratory of a hospital or Urologists' office. Residual Urine Volume Residual urine is the amount of urine left inside the bladder after a complete voiding. Normally, no urine should be left in the bladder but varying amounts of residual urine can result from prostatic urethral obstruction or reduced detrussor contractility. It can easily be assessed with the use of ultrasound with pre and post void scans or immediate catheterization following completion of urination. Patients with a large amount of residual urine ( cc.) may not respond to medical treatment but may instead require surgery. Pathogenesis The exact cause of BPH is unknown. Two important factors have been observed in men with BPH and these are: Androgen-producing testes The influence of age The role of other factors in the pathogencsis of BI'll evolves around the androgens such that five theories are siiggt'strd. 1 he mechanism of action of some pharmacologu agents iirc hasnl on some of these five concepts (Table 5 - Appendix) International Symptom Score Assessment of Urinary Symptoms based on International Prostate Symptom Score This IPSS is designed to determine or quantify the severity of symptoms. Decisions on treatment will usually be

7 based on whether the symptoms are mild, moderate or severe (Figure 4 - Appendix). Its use is highly recommended not only before but also during treatment, to monitor treatment response. It contains 7 questions or items with 6 possible answers to which points are assigned depending on the severity of the symptoms, so that the maximum score is 35 (Figure 5 - Appendix). The quality of life assessment (QOLA) has only one question with answers ranging from delighted to terrible or 0-6 (Figure 6 - Appendix). IPSS: Significance of Total Score to Treatment (See Figure 4 - Appendix) Mild Symptoms (0-9) - Patients in this category have less bothersome symptoms and generally, do not require treatment. Watchful Waiting (Wawa) is usually in order for these patients. They are re-evaluated every 6-12 mos. with IPSS and DRE. Moderate (10-19) - Patients in this category could be successfully treated with pharmacologic agents. These agents differ in the mechanisms of action, onset of action, adverse effects and cost. Severe symptoms (20-35) - Most patients in this category will need surgical intervention and, therefore should be referred to a Urologist for proper workup and treatment. Treatment The traditional surgical intervention by a urologist in the treatment of BPH is now replaced by a trial of pharmacologic agents by general practitioners. There are now several options in the treatment of BPH that one may try before considering surgery (Figure 7 - Appendix). Before initiating medical treatment it is important that a diagnosis of uncomplicated BPH with moderate symptom score be made. During treatment, monitoring for response and adverse effects of the drug is important. It is recommended that treatment be discontinued if any of the following is observed. No improvement in subjective or objective parameters after adequate duration of treatment. Interim changes in DRE or TRUSP findings Abnormal behaviour of PSA, PSA velocity. Drug Therapy The pharmacological agents used in the treatment of BPH fall into 4 categories (Table 8 - Appendix). Anti-androgens: The rationale in the use of antiandrogens for BPH is based upon the concept that testicular androgen is necessary in the development of BPH. Clinical trials with these agents demonstrate an average reduction of prostate size by 30%. They are more popularly used in the treatment of advanced cancer of the prostate than BPH. 5-Alpha reductase inhibitor (Finasteride) is the most extensively studied anti-androgen for BPH. Its main effects include significant reduction in serum and prostatic DHT inducing considerable prostatic involution producing 30-40% decrease in prostate volume in 3-6 months treatment. It is given at 5 mg daily with impotence and loss of libido as the main adverse effects occuring in up to 5% of patients. It is also known to reduce PSA by 50% (Table 9 - Appendix). Alpha-Adrenergic Blockers or antagonists have been in clinical use for the last 25 years. Initially, their use was mainly as 2nd or 3rd line treatment for hypertension but improvement in their pharmacology led to the widespread use as 1st line treatment for hypertension and more recently, for the symptomatic treatment of BPH. Their use has been endorsed by both the International Consultation on BPH and US Agency for Health Care Policy and Research. Two types of alpha adrenergic blockers are available in the market: Long Acting: Doxazosin, Terazosin, Tamsulosin Short Acting: Alfuzosin, Prazosin In general, long acting alpha-block\ers are usually given at bedtime and require gradual dose titration over a period of 2 to 3 weeks, improve most symptoms of prostatism, are effective in 60% of patients and increase urine flow by 3-5 ml/sec. Drowsiness, headaches are seen in 10-15% of cases, postural hypotension in 2-5%. Uroselective blockers like Alfuzosin may ha ve a rapid onset of action in "90 minutes". If no improvement is seen within 2 to 4 months despite adequate dose, alternative titration therapy should be considered (Table 8 - Appendix). Alpha Adrenergic Blockers: Terazosin 1-10 mg daily at bedtime; titrated over 2-3 weeks period, locally available tablets of 1 to 5 mg. Alfuzosin 2.5 mg 1 tab 3 x a day. No dose titration is necessary. Doxazosin 4-8 mg daily at bedtime. Tamsulocin 0.4 mg daily at bedtime. Fraction Binders: Evidence shows that estrogen plays a significant role inpathogenesis of BPH and that investigators have shown that the combined biological effects of estrogen and androgen within the human prostate promotes stromal hyperplasia that can lead into clinical obstructive adenoma. Mepartricin (Ipertrofan), a semisynthetic derivative of a polyene antibiotic isolated from Streptomyces aureofaciens 391

8 culture, binds irreversibly with androgen and estrogenic steroids in the gastrointestinal tract leading to increased fecal excretion of the mepartricin-steroid complex which in turn results in somewhat serum testosterone - estrogen ratio. It is widely used in some countries in Europe. Usual dose is 50,000 'U'-T tablet TID. It reduces prostate volume without affecting libido or potency. Controlled clinical studies showed significant improvement in symptom score, peak urine flow and residual urine volume. It is currently being evaluated in line with the guidelines recommended by the International Consultation on BPH for Diagnosis and Treatment of BPH. Phytotherapy: The use of plant extracts is the oldest form of treatment for BPH. Some investigators claim that they are effective for the relief of symptoms and have minimal side effects. The locally available agent is Pygeum africanum (Tadenan) given at 50 mg 2x a day. It targets the prostate and the bladder inhibiting b-fgf induced fibroblast proliferation improving bladder contractility and reducing tissue rigidity from fibrosis. No adverse effect on sexuality. Minimally Invasive Procedures Minimally Invasive Treatment Alternatives Modem and highly technological devices are used in this treatment alternative of BPH. Only a few of these devices are locally available at this time, and are mainly indicated for those patients who cannot undergo surgery because of medical contraindications (Table 6 - Appendix). CPM 1 ST EDITION V-LAF= Visual laser ablation of the prostate. Its main advantages are minimal blood loss, very short operative time, minimal complications. Long term effects are not known at this time. Thermotherapy = uses urethral microwave catheter to deliver heat to the prostate over 45 o C. It has very minimal complications and can be performed as an out-patient procedure without anesthesia but the short and long term results are lacking. Use of Urethral Stents = They are used to mechanically distend the prostatic urethra thereby relieving the obstruction. Electrovaporization of the Prostate = vaporization of the prostatic tissues is accomplished by means of a roller bar or ball (vaportrode). It has also minimal complications and a short operative time but the main disadvantage is the lack of a specimen for histopathological examinations. Surgical Options Generally, surgery to the prostate for BPH have been refined which could be carried out through the conventional "open" method or "closed" transurethral method. Although the rate of Transurethral Resection of the Prostate (TURP) has significantly been reduced in the last decade because of medical agents, it is still considered as the gold standard in the treatment of BPH. While surgery is the most effective form of treatment, it, however, carries a high risk of complications and morbidity and hospitalization is necessary. This option is indicated for a certain group of patients (Figure 7, Table 7 - Appendix). Medical Therapy for BPH Agent Dose Onset of Mechanism of Adverse action action effects 5-alpha Finasteride 5 mg/day 3-6 mths reductase Prostate volume Impotence inhibitors (3-5%) Epristeride 80mg/day 3-6 mths Reverse BPH Alpha-1 Prazosin 2 mg/day 2-4 weeks Relax Drowsiness blockers Doxazosin 4 mg/day prostatic & headache Alfuzosin 7.5 mg/day smooth muscle (10-15%) Terazosin 5 mg/day Dizziness Tamsulosin 0.4 mg/day Postural hypotension (2-5%) Adopted from Shared Care for Prostatic Diseases: R and M Kirby, ] and AFitzpatrick IS IS Medical Media,

9 Appendix A. Figures Figure 1: Candidates for Surgical Treatment (Urologists' Cases) 1. Patients with urinary retention 2. Patients with hematuria (gross/microscopic) 3. Patients with azotemia (elevated BUN, Creatinine) 4. Patients with abnormal PSA and DRE findings (suspected CA) 5. Patients with dilated upper urinary tract 6. Patients with acute/chronic urinary tract infection 7. Patients not responding to medical agents. Figure 2: Mandatory Procedures in the Initial Evaluation of Patients with BPH Complete medical history General Physical Examination Examination of the abdomen focusing on the kidneys and urinary bladder Digital Rectal Examination Urinalysis Serum BUN and Creatinine Serum PSA Strongly Recommended Tests Residual urine determination by ultrasound Urine Flow Rate Figure 3: Neurologic Examination in Urology Upper Motor Neuron Lesion (Central Lesions) Hyperactivity: Deep Tendon Reflexes Muscular Reflexes Spasticity: Skeletal muscles Pathologic Toe Signs: Babinski Lower Motor Neuron Lesion (Peripheral Lesion) Absent Deep tendon and muscular reflexes Skeletal flaccidity Absent abnormal toe signs Conal Activity Anal Sphincter (S3-S5) Anal Reflex (S5) Bulbocavernosus Reflex (L5-S5) Figure 4: IPSS: Significance of Total Score to Treatment 0-9 = mild symptoms = moderate symptoms = severe symptoms Figure 5: International Prostate Symptom Score never less than less around more nearly l in than half half the than half always 5 times the time time the time 1. In the past month, how often did you have the feeling that your bladder was not yet empty after you had urinated? In the past month, how often did you need to urinate again within two hrs of having gone to the toilet? In the past month. How often did you notice that the flow stopped a few times and then started again during urination? In the past month, how often did you have difficulty in postponing urination? In the past month, how often did you have a weak urine flow? In the past month, how often did you have to push to start a urine flow? times never once twice 3 times 4 times or more 7. In the past month, how often did you have to get up at night to urinate?

10 Figure 6: Quality of Life based on symptoms of the urinary tract CPM 1 ST EDITION mixed feelings generally happy pleased generally (it makes no discon- un- terrible contented difference) tented happy If urination were to stay as it is now for the rest of your life how would this make you feel? quality of life score: S= Figure 7: Treatment Options for BPH: 1. Watchful Waiting (Wawa) 2. Pharmacologic Agents 3. Minimally Invasive Procedure 4. Surgery B. Tables Table 1: Signs and Symptoms of Prostatism due to BPH: Obstructive Irritative Symptoms Symptoms 1. Hesitancy and Straining 1. Frequency 2. Weak Stream 2. Nocturia 3. Prolonged and interrupted 3. Urgency stream 4. Urgency 4. Sensation of Residual Urine incontinence 5. Urinary retention and overflow incontinence Table 2: PSA = Age Specific Normal Range Age range (yes) PSA ng/ml Table 3: PSA Range and Prostate Cancer Range Consideration 0-4 ng/ml normal 5-10 ng/ml elevated (abnormal) 20% chance of prostate cancer >10 ng/ml very abnormal 60% chance of prostate cancer Table 4: Maximum Flow Rate Values Flow Rate Interpretation >15 ml/sec normal ml/sec equivocal <10 ml/sec obstruction Table 5: Concepts in the Development of BFH Theory Cause Effect DHT 5-alpha reductase Epithelial & hypothesis and androgen stromal receptors hyperplasia Oestrogen- Oestrogens Stromal testosterone Testosterone hyperplasia imbalance Stromal- Epidermal growth Epithelial & epithelial factor/fibroblast stromal interactions growth factor hyperplasia Transforming growth factors B Reduced cell Oestrogens Longevity death of stroma & epithelium Stem cell Stem cells Proliferation theory of transit cells Adopted from Shared Care for Prostatic Diseases: R and M Kirby, J and A Fitzpatrick ISIS Medical Media, 1994 Table 6: Minimally Invasive Treatments for BPH I. Coagulation II. Electrosurgical Necrosis Vaporization Radiofrequency (TUNA) III. Prostatic Devices Interstitial Laser Therapy Endourethral High Intensity Focus prosthesis Ultrasound (HIFU) (Urolume) Microwave thermo- Intraprostatic therapy (>45 C) Stents (Titan) Hyperthemia (<45 C) Prostacath Stents Visual Laser Ablation Urospiral Stents Others 394

11 Table 7: Surgical Options in BPH Suprapubic Prostatectomy Retropubic Prostatectomy Perineal Prostatectomy Transurethral Resection of the Prostate (TURP) Transurethral Incisions of the Prostate (TUIP) Table 8: Medical Treatment of BPH Pharmacologic Agents I. Anti-Androgens: III. Estrol Fraction 1. LHRH Agonists Binders: 2. Progestins 1. Mepartricin 3. Cyproterone Acetate 2. Testolactone 4. Flutamide 3. Atomestone 5. Finasteride II. Alpha-Adrenergic IV. Phytotherapy: blockers: Extracts from 1. Terazosin l. Pygeum africanum 2. Alfuzosin 2. Serenoa repens 3. Doxazosin 3. Populus fremula 4. Tamsulocin 4. Others Urology 29 (Suppl. 1) 2-6,1996. M. Caine: Alpha-Adrenergic Blockers for the Treatment of Benign Prostatic Hyperplasia: The Uro. Clinics of N.A. 17, No. 3,641-47; August L.J. Denis, R. Chris, P. Francisco, et al: Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial Mepartricin in the Treatment of Men with BPH. Six Months Follow-up. Presented at the XII Congress of the European Association of Urology, September 1-4, Paris, France. H. Lepor: The Efficacy of Terazosin, Finasteride or Both in BPH: New England J. of Medicine 335, No. 8, , August 22,1996. Table 9: Locally Available Anti-Androgen and Adverse Effects Anti-Androgen: Adverse Reactions: LHRH Agonists Gynecomastia, Loss of Libido, Progestins hot flashes Cyproterone Acetate Loss of libido, impotence, heat Flutamide intolerance Finasteride Impotence, loss of libido Tender nipples, loss of libido Loss of libido, impotence Bibliography: L. J. Denis and K. Griffiths (Editors): Insights into BPH compiled by Complit Systems Ltd, P.O. Box 630, Cardiff, U.K. R. and M. Kirby, J. and A. Fitzpatrick: Shared Care for Prostatic Diseases, 1994 ISIS Medical Media Ltd. Saxon Beck, 58 St. Aldates, Oxford Oxi 1st; U.K, James L. Pool: Unique Aspects of Doxazosin: A Third Generation Alpha- Blocker. European Urology: 29 Sl, March Roger S. Kirby: Doxazosin: Safety Relative to Other Medical Therapies for Benign Prostatic Hyperplasia. European Urology 29:S1, March John D. McConnel, M.D.: Androgen Ablation Blockade in thetreatment of Benign Prostatic Hyperplasia: Urologic Clinics of North America: 17,3, August H. Lepor, S. Auerback, A. Puras-aez, et al: A Randomized Placebo Controlled Multicenter Study of the Efficacy and Safety of Terazosin in the Treatment of BPH: J. Urology 148, , November T. Lotti, J. Mironi, D. Prezioso et al: Observations on Some Hormone Fractions in Patients with BPH Treated with Mepartricin: Current Therapeutic Research 44, No. 3, September J.E. Altwein: Individualization of Treatment in BPH. European 395

12 Drugs Mentioned in the Treatment Guideline Anti-androgens Cyproterone Androcur Flutamide Fugerel Finasteride Proscar Gestonorone Primostat Alpha-Adrenergic Blockers Alfuzosin Xatral Doxazosm Carduran Terazosin Hytrin Estrol Fraction Binders Mepartricin Ipertrofan Phytotherapy Pygeum africanum Tadenan The following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's reference, available drugs are listed under each therapeutic class. 396