1. The Medical Therapy Of Prostatic Symptoms (MTOPS) Trial: Results
Despite the well-established benefits of 5-alpha reductase inhibitors and alpha blockers, defining the optimal medical approach to preventing the progression of benign prostatic hyperplasia (BPH) continues to challenge clinicians.1 This slide presentation reviews the issues surrounding pharmacotherapy for BPH and presents the design and results of the recently completed Medical Therapy Of Prostatic Symptoms (MTOPS) study. The largest randomized, placebo-controlled clinical trial ever conducted in men with BPH compared long-term medical therapy with a 5-alpha reductase inhibitor, an alpha blocker, and their combination with placebo.1  
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2. Medical Treatment of BPH: The Challenge
BPH is the most common benign neoplasm in older men
Clinical BPH involves benign prostatic enlargement, lower urinary tract symptoms (LUTS), and bladder outlet obstruction
BPH can interfere with daily activities and can diminish health-related quality of life specific to urinary symptoms
The most common benign neoplasm in older men,1 BPH in its narrowest definition is characterized by histopathologically demonstrated hyperplastic changes in the prostate.2 When clinicians use this term, however, the definition also includes lower urinary tract symptoms (LUTS) and bladder-outlet obstruction.2 BPH is a considerable problem not only because of these signs and symptoms,2 but also because it can interfere with daily activities and can have a negative impact on health-related quality of life specific to urinary symptoms.3 BPH can eventually progress to serious long-term consequences including acute urinary retention (AUR) and the need for BPH-related surgery.2
BPH=benign prostatic hyperplasia
Adapted from Bautista OM et al Control Clin Trials 2003;24: ; Emberton M et al Urology 2003;61(2): ; Girman CJ et al Eur Urol 1999;35:
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3. Medical Treatment of Clinical BPH
Recommendations of the 5th International Consultation on BPH in 2001
Medical Treatment of Clinical BPH
Short-term
Improve symptoms
Long-term
Prevent complications
In 2001, the International Consultation on BPH (ICBPH) published recommendations for evaluation and treatment based on a thorough literature review and the opinion of recognized experts.4 The guidelines stipulate that medical treatment of BPH should improve symptoms, prevent long-term complications, and have minimal morbidity (i.e., produce minimal side effects and preserve quality of life).4 Treatment of BPH should therefore go beyond immediate relief of symptoms to address the possibility of future complications.5
Overall
Minimize adverse effects of treatment
Preserve quality of life
Adapted from Chatelain C et al 5th International Consultation on BPH 2001:
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4. Medical Treatment of Clinical BPH
Recommendations of the 5th International Consultation on BPH in 2001
Medical Treatment of Clinical BPH
5-alpha reductase inhibitors and alpha blockers are the only recommended medical treatments of BPH
Recommendations for phytotherapy or polyene derivatives require additional long-term data
The 2001 ICBPH guidelines recommend only two forms of medical treatment for BPH—5-alpha reductase inhibitors and alpha blockers— in patients without serious complications.4 The possible benefits of phytotherapeutic preparations and polyene derivatives are acknowledged, but the guidelines call for additional long-term data before such treatments can be recommended.4
Adapted from Chatelain C et al 5th International Consultation on BPH 2001:
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5. 5-Alpha reductase inhibitors
Could Combination Therapy Be a Better Approach? Two-Drug Therapy Activates Two Distinct and Complementary Mechanisms of Action
Alpha blockers
5-Alpha reductase inhibitors
The two most commonly used medical treatments of BPH—5-alpha reductase inhibitors and alpha blockers—target different aspects of BPH pathology.6 Alpha blockers improve symptoms and increase urinary flow rate by relaxing prostatic and bladder-neck smooth muscle through blockade of sympathetic input into alpha1-adrenergic receptors.6,7 5-Alpha reductase inhibitors improve symptoms, increase urinary flow rate, and prevent BPH outcomes by reducing prostate enlargement through hormonal mechanisms; i.e., suppression of the conversion of testosterone into dihydrotestosterone (DHT).6
In light of these different pathophysiologic approaches, the combined use of these drug classes has been the focus of BPH research aimed at improving the efficacy of either treatment used alone.6
Improve symptoms and increase urinary flow rate by relaxing prostatic and bladder-neck smooth muscle through sympathetic activity blockade
Improve symptoms, increase urinary flow rate, and prevent BPH outcomes by reducing prostate enlargement through hormonal mechanisms
Adapted from Roehrborn CG Curr Opin Urol 2001;11:17-25; National Cancer Institute. NIH Publication No , 1999.
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6. Evidence on Combination Therapy
Most trials of 5-alpha reductase inhibitor + alpha-blocker therapy were of short duration or lacked placebo controls
Two randomized, placebo-controlled, multicenter, 12-month studies showed that combination therapy did not enhance the efficacy of alpha-blocker monotherapy in terms of improving symptoms or urinary flow rate
VA COOP: Placebo vs. PROSCAR™ vs. terazosin vs. combination in 1229 men with BPH in US VA system
PREDICT: Placebo vs. PROSCAR vs. doxazosin vs. combination in 1095 men with BPH in Europe
Until recently, clinical trials of combination therapy for BPH with a 5-alpha reductase inhibitor plus an alpha blocker have yet to yield definitive results. Methodologic limitations such as lack of placebo controls or short duration, or both, were common.6,8,9 Only two large-scale,12-month, randomized, multicenter, placebo-controlled studies were conducted— the Veterans Affairs Cooperative (VA COOP) trial and the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Both showed that combination therapy did not enhance the efficacy of alpha- blocker monotherapy by improving symptoms or urinary flow rate.10,11 However, it has been noted that both studies were of short duration (1 year) and only measured alterations in symptoms.12
To assess the merits of combination therapy for BPH with the 5-alpha reductase inhibitor PROSCAR™ plus an alpha blocker, the US National Institutes of Health (NIH) initiated the MTOPS trial.1 The following slides discuss its design and results.
PROSCAR (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
PROSCAR (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
VA COOP=Veterans Affairs Cooperative; PREDICT=Prospective European Doxazosin and Combination Therapy
Adapted from Roehrborn CG Curr Opin Urol 2001;11:17-25; Debruyne FMJ et al Eur Urol 1998;34: ; Savage SJ et al Can J Urol 1998;5(3): ; Lepor H et al N Engl J Med 1996;335(8): ; Kirby RS et al Urology 2003;61(1):
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7. Independently Conducted by the US National Institutes of Health (NIH)
MTOPS (Medical Therapy Of Prostatic Symptoms)
Objective of MTOPS
To determine whether long-term medical therapy with PROSCAR™, the alpha blocker doxazosin, or their combination would prevent or delay the clinical progression of BPH
As defined in the NIH protocol, the primary objective of the MTOPS study was to determine whether long-term medical therapy with PROSCAR™, the alpha blocker doxazosin, or their combination would prevent or delay the clinical progression of BPH.1
Independently Conducted by the US National Institutes of Health (NIH)
Adapted from Bautista OM et al Control Clin Trials 2003;24:
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8. Study Design: Overview
MTOPS (Medical Therapy Of Prostatic Symptoms)
Study Design: Overview
Double-blind, placebo-controlled, multicenter, randomized Average follow-up: 4.5 years
Randomized N=3047 Entry Criteria
Men 50 years of age
AUA symptom score 8–30
Qmax 4–15 ml/sec
Voided volume 125 ml
MTOPS was a prospective, double-blind, placebo-controlled, multicenter, randomized clinical trial.1 MTOPS was the longest, largest trial of medical management of BPH. Unlike some previous trials of combination therapy, which have been of shorter duration and of more limited scope (evaluation of symptoms only),12 MTOPS evaluated overall BPH progression over an average follow-up of 4.5 years.1
The MTOPS trial enrolled men at least 50 years of age with moderate to severe symptoms of BPH (American Urological Association Symptom Index [AUA-SI] of 8–30), maximum urinary flow (Qmax) of 4 to 15 ml/second, and a voided volume of at least 125 ml. Prior medical, surgical, or experimental interventions for BPH were reasons for exclusion.1
The 3047 eligible men were randomly assigned to doxazosin 4–8 mg/day (n=756), PROSCAR™ 5 mg/day (n=768), PROSCAR 5 mg/day + doxazosin 4–8 mg/day (n=786), or placebo (n=737) for an average follow-up of 4.5 years. Treatment with doxazosin began at 1 mg/day and increased to 2, 4, and 8 mg/day, with each dose taken for one week. The goal was 8 mg/day, but patients unable to tolerate this dosage were allowed to receive 4 mg/day. All medications (including placebo) were taken once daily at bedtime.1
Doxazosin (n=756)
PROSCAR™ (n=768)
PROSCAR + doxazosin (n=786)
Placebo (n=737)
AUA=American Urological Association; Qmax=maximum urinary flow
Adapted from Bautista OM et al Control Clin Trials 2003;24:
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9. Study Design: Outcomes
MTOPS (Medical Therapy Of Prostatic Symptoms)
Study Design: Outcomes
Clinical progression of BPH
Confirmed 4-point increase in AUA-SI
AUR
Recurrent urinary tract infections/ urosepsis
Urinary incontinence
Renal insufficiency
Natural history of BPH with respect to
BPH symptoms
Qmax
Prostate volume
Sexual function
Quality of life
Primary
outcome
The primary outcome measure in MTOPS was clinical progression of BPH based on symptoms and other biologic indicators.1 BPH was defined as having progressed if any of the following occurred:
 A substantial worsening of symptoms (increase in AUA-SI of four or more points from baseline)
– Although a 3-point reduction is generally accepted as clinically significant,13 investigators didn’t know whether a 3-point increase in symptom score would equate with clinical deterioration. Thus, the investigators chose a threshold of 4 points, which had to be verified within 2 to 4 weeks.14
 An episode of AUR (inability to urinate requiring catheterization)
 Recurrent urinary tract infections (two infections within one year documented by culture and separated by antibiotic therapy) or a single episode of urosepsis due to bladder-outlet obstruction documented by culture
 An episode of incontinence (self-reported involuntary loss of urine that was socially or hygienically unacceptable)
 BPH-associated renal insufficiency (serum creatinine concentration 1.5 mg/dl and 50% increase from baseline)
Secondary outcomes, evaluated to assess the natural history of BPH, included BPH symptoms, Qmax, prostate volume, sexual function, and quality of life.1
Secondary
outcome
AUA-SI=American Urological Association Symptom Index; AUR=acute urinary retention
Adapted from Bautista OM et al Control Clin Trials 2003;24:
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10. Baseline Characteristics of Patients
MTOPS (Medical Therapy Of Prostatic Symptoms)
Baseline Characteristics of Patients
Characteristic Value*
Age (years) 62.0
AUA-SI score 17.0
TRUS Prostate volume (cc) 31.0
Postvoid residual urine volume (ml) 39.0
Qmax (ml/second) 10.6
The treatment groups were well matched at baseline and did not differ significantly from one another. The median age of patients was 62 years, and the median AUA symptom score was 17.0 points. Median prostate volume was 31.0 cc. Median postvoid residual urine volume was 39.0 ml, and the median Qmax (maximal urinary flow rate) was 10.6 ml/second.15
No significant differences between groups
AUA=American Urological Association; TRUS=transrectal ultrasound
*Values are medians
Adapted from McConnell JD et al N Engl J Med 2003;349(25):
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11. Impact of Medical Therapy on Clinical Progression of BPH
MTOPS (Medical Therapy Of Prostatic Symptoms)
Impact of Medical Therapy on Clinical Progression of BPH
Cumulative incidence of BPH progression 25 20 15 10 5
Placebo (n=737)
PROSCAR™ (n=768)
Doxazosin (n=756)
Combination (PROSCAR + doxazosin) (n=786)
Data from up to 5.5 years of follow-up in MTOPS showed that combination therapy with PROSCAR™ and doxazosin was effective in providing a 66% reduction in risk of BPH progression versus placebo—significantly greater than that with either drug alone (p<0.001). Both monotherapy groups also significantly reduced the risk of BPH progression versus placebo by 34% with PROSCAR (p=0.002) and by 39% with doxazosin (p<0.001). There was no significant difference in risk reduction between the doxazosin monotherapy arm and the PROSCAR monotherapy arm.15
Combination therapy was superior to monotherapy in reducing the risk of BPH progression (p0.0004) at 4 years. Combination therapy reduced the risk of BPH progression by 49% versus PROSCAR (p<0.0001) and by 46% versus doxazosin (p=0.0004).16
66% risk reduction (p<0.001)
p=0.002
Percentage with event
p<0.001
p<0.001
Years from randomization
P values are for the comparison with placebo.
Adapted from McConnell JD et al N Engl J Med 2003;349(25): ; Bautista OM et al Control Clin Trials 2003;24:
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12. Most BPH Progression Events Were Due to Symptom Progression
MTOPS (Medical Therapy Of Prostatic Symptoms)
Most BPH Progression Events Were Due to Symptom Progression
Distribution of BPH progression events
UTI/urosepsis 1% Renal insufficiency 0%
Incontinence 7%
In MTOPS, 80% of BPH progression events were due to substantially increased symptom scores. The remaining events were attributable to AUR (12%), incontinence (7%), and urinary tract infections or urosepsis (1%). No patient experienced renal insufficiency due to BPH.15
AUR 12%
>4-point AUA-SI increase 80%
UTI=urinary tract infection
Adapted from McConnell JD et al N Engl J Med 2003;349(25):
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13. Impact of Medical Therapy on Symptom Control
MTOPS (Medical Therapy Of Prostatic Symptoms)
Impact of Medical Therapy on Symptom Control
Cumulative incidence of 4-point increase in symptom score* 25 20 15 10 5
Placebo (n=737)
PROSCAR™ (n=768)
Doxazosin (n=756)
Combination (PROSCAR + doxazosin) (n=786)
Substantial worsening of symptoms was defined as a confirmed increase of four or more points in the AUA score. Combination therapy with PROSCAR™ and doxazosin reduced the risk of substantial symptom worsening by 64% versus placebo (p<0.0001) at 4 years.15-17
Combination therapy also was superior to monotherapy with either component in reducing the risk of worsening symptoms:16 risk reductions with combination therapy were 48% versus PROSCAR (p=0.0006) and 34% versus doxazosin (p=0.0369). There was no significant difference in risk reduction between the doxazosin monotherapy arm and the PROSCAR monotherapy arm.
64% risk reduction (p<0.0001)
Percentage with event
Years from randomization
*AUA-SI score
Adapted from McConnell JD. Presentation at AUA Annual Meeting, Orlando, Florida, USA, May 2002; Bautista OM et al Control Clin Trials 2003;24:
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14. Effect of Medical Therapy on Prostate Volume
MTOPS (Medical Therapy Of Prostatic Symptoms)
Effect of Medical Therapy on Prostate Volume
Change from baseline in prostate volume
Combination (PROSCAR™ + doxazosin) (n=786)
–13%*
PROSCAR (n=768)
Both combination therapy and monotherapy with PROSCAR™ produced significant reductions in prostate volume from baseline at 4 years (p<0.001). At 4 years, prostate volume decreased by 13% with combination therapy and by 16% with PROSCAR compared with baseline; prostate volume increased from baseline by 18% in both the placebo and doxazosin monotherapy groups at 4 years.17
These results reflect the different mechanisms of action of 5-alpha reductase inhibitors and alpha blockers. By decreasing DHT, PROSCAR causes epithelial cell atrophy and programmed cell death (apoptosis) in prostatic tissue that lead to an overall reduction in prostate volume.5,6 In contrast, rather than affecting the histologic structure of the prostate, alpha blockers such as doxazosin relax smooth muscle in the prostate and bladder neck.6
–16%*
Doxazosin (n=756)
+18%
Placebo (n=737)
+18%
–20
–10 10 20
Median % change from baseline
*p<0.001 vs. baseline
Adapted from McConnell JD. Presentation at AUA Annual Meeting, Orlando, Florida, USA, May 2002; Bautista OM et al Control Clin Trials 2003;24:
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15. Impact of Medical Therapy on the Risk of AUR
MTOPS (Medical Therapy Of Prostatic Symptoms)
Impact of Medical Therapy on the Risk of AUR
Cumulative incidence of AUR
Placebo (n=737)
PROSCAR™ (n=768)
Doxazosin (n=756)
Combination (PROSCAR + doxazosin) (n=786)
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Combination therapy with PROSCAR™ and doxazosin significantly reduced the risk of AUR by 81% versus placebo (p<0.001) at 4 years. The risk of AUR also decreased significantly—by 68%—with PROSCAR alone versus placebo (p=0.009), but not with doxazosin alone versus placebo (p=NS).15
Combination therapy reduced the risk of AUR by 37% versus PROSCAR (p=NS) and significantly reduced the risk of AUR by 70% versus doxazosin (p=0.0214) at 4 years.16
MTOPS also showed that administering doxazosin alone over time (up to 5 years) did not significantly reduce the risk of AUR.15 According to John McConnell, MD, this indicates that the alpha-adrenergic-mediated smooth muscle tone is not the only factor underlying the development of problems with urethral resistance, which is what accounts for urinary retention.18
81% risk reduction (p<0.001)
Percentage with event
p=0.009
p<0.001
Years from randomization
Adapted from McConnell JD et al N Engl J Med 2003;349(25): ; Bautista OM et al Control Clin Trials 2003;24:
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16. Impact of Medical Therapy on the Need for Invasive BPH Therapy*
MTOPS (Medical Therapy Of Prostatic Symptoms)
Impact of Medical Therapy on the Need for Invasive BPH Therapy*
Cumulative incidence of BPH-related surgery 10 8 6 4 2
Placebo (n=737)
PROSCAR™ (n=768)
Doxazosin (n=756)
Combination (PROSCAR + doxazosin) (n=786)
Over the duration of the study, combination therapy with PROSCAR™ and doxazosin significantly reduced the need for invasive therapy for BPH by 67% versus placebo (p<0.001) at 4 years. Most types of invasive therapies for BPH were endoscopic (e.g., transurethral prostatectomy) or open surgeries; the others were minimally invasive, e.g., transurethral microwave therapy.15
A significant reduction of 64% occurred with monotherapy with PROSCAR versus placebo (p<0.001) at 4 years. Doxazosin monotherapy, in contrast, did not significantly reduce the incidence of BPH-related surgery versus placebo.15
67% risk reduction
(p<0.001)
Percentage with event
p<0.001
p<0.001
Years from randomization
*Endoscopic (e.g., transurethral prostatectomy) or open surgeries primarily; other therapies were minimally invasive (e.g., transurethral microwave therapy)
Adapted from McConnell JD et al N Engl J Med 2003;349(25): ; Bautista OM et al Control Clin Trials 2003;24:
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17. Ten most frequent adverse events among groups*
MTOPS (Medical Therapy Of Prostatic Symptoms)
Medical Monotherapy and Combination Therapy Demonstrated Long-Term Tolerability
Ten most frequent adverse events among groups*
PROSCAR Placebo Doxazosin PROSCAR™ and doxazosin Variable (n=737) (n=756) (n=768) (n=786)
In MTOPS, the adverse events seen with the combination of PROSCAR™ and doxazosin were similar to those with each drug used alone in previous trials.15 Dizziness, the most common adverse event with combination therapy, occurred in 5.4% of patients (p<0.05 vs. placebo).
Rates of discontinuation of PROSCAR were similar to those of doxazosin (data not shown).15 There were no new or unexpected adverse events noted in the combination arm of the study.
For full details of the tolerability profile, please refer to the product circular issued by the manufacturer.
Total no. of person-years
Adverse Event Erectile dysfunction ** 5.1** Dizziness ** **
Postural hypotension ** **
Asthenia ** **
Decreased libido ** 2.5**
Abnormal ejaculation ** 3.1**
Peripheral edema **
Dyspnea **
Allergic reaction **
Somnolence ** **
*The numbers shown are the rates per 100 person-years of follow-up (incidence density) as of September 30, 2002; **p<0.05 vs. placebo
Adapted from McConnell JD et al N Engl J Med 2003;349(25): ; Bautista OM et al Control Clin Trials 2003;24:
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18. MTOPS (Medical Therapy Of Prostatic Symptoms)
Conclusions
Combination therapy is the most effective form of medical therapy for BPH
66% reduction in risk of BPH progression (p<0.001*)
64% reduction in worsening symptoms (p<0.001*)
81% reduction in risk of AUR (p<0.001*)
67% reduction in need for invasive BPH therapy (p<0.001*)
Long-term monotherapy and combination therapy were well tolerated and effective
MTOPS, the longest and largest trial of medical management of symptomatic BPH conducted to date,14 proved that combination therapy with PROSCAR™ and the alpha blocker doxazosin was the superior option. Combination therapy significantly reduced the risk of clinical outcomes at 4 years: by 66% in BPH progression, 64% in worsening symptoms, 81% in AUR, and 67% in need for invasive BPH therapy (all p<0.001 vs. placebo).15 Over an average follow-up of 4.5 years,1 both monotherapy and combination therapy were well tolerated and effective.15
*vs. placebo at 4 years
Adapted from McConnell JD et al N Engl J Med 2003;349(25):
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19. The Future of Combination Therapy for BPH
“The evidence supporting combination therapy [for BPH] in selected patients is so strong that I expect to see major changes in medical practice in the near future.”
MTOPS established that PROSCAR™ and the alpha blocker doxazosin are more effective in combination than alone to prevent the progression of BPH. According to the MTOPS trial leader John McConnell, MD, “Combination therapy not only provides better long-lasting symptom relief, but because finasteride reduces prostate size, patients have fewer episodes of urinary retention and invasive treatments.” Leroy M. Nyberg Jr, PhD, MD, a spokesman for the National Institute of Diabetes and Digestive and Kidney Diseases, which funded the study, summed up the future of BPH treatment based on the MTOPS findings. “This is the kind of clear-cut result we all strive for when we launch a clinical trial. The evidence supporting combination therapy in selected patients is so strong that I expect to see major changes in medical practice in the near future.”19
Leroy M. Nyberg Jr, PhD, MD
Director, Urology Program
National Institute of Diabetes and Digestive and Kidney Diseases
Adapted from NIH news release. Available at:
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20. References Please refer to notes page. PSC 2004-W-14295-SS References
Bautista OM, Kusek JW, Nyberg LM Jr et al, for the MTOPS Research Group. Study design of the Medical Therapy Of Prostatic Symptoms (MTOPS) trial. Control Clin Trials 2003;24:
Emberton M, Andriole GL, de la Rosette J et al. Benign prostatic hyperplasia: A progressive disease of aging men. Urology 2003;61(2):
Girman CJ, Jacobsen SJ, Rhodes T et al. Association of health-related quality of life and benign prostatic enlargement. Eur Urol 1999;35:
Chatelain C, Denis L, Foo JKT et al. 5th International Consultation on BPH, Recommendations of the International Scientific Committee: Evaluation and Treatment of Lower Urinary Tract Symptoms (LUTS) in Older Men. Geneva: WHO, 2001:
Holtgrewe HL. The medical management of lower urinary tract symptoms and benign prostatic hyperplasia. Urol Clin North Am 1998;25(4):
Roehrborn CG. Is there a place for combination medical therapy? Curr Opin Urol 2001;11:17-25.
National Cancer Institute. Understanding Prostate Changes: A Health Guide for All Men. Bethesda, MD: US Department of Health and Human Services, NIH Publication No
Debruyne FMJ, Jardin A, Colloi D et al on behalf of the European ALFIN Study Group. Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. Eur Urol 1998;34:
Savage SJ, Spungen AM, Galea G et al. Combination medical therapy for symptomatic benign prostatic hyperplasia. Can J Urol 1998;5(3):
Lepor H, Williford WO, Barry MJ et al, for the Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. N Engl J Med 1996;335(8):
Kirby RS, Roehrborn C, Boyle P et al, for the PREDICT Study Investigators. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: The Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 2003;61(1):
McVary KT. Medical therapy for benign prostatic hyperplasia progression. Curr Urol Reports 2002;3:
Barry MJ, Williford WO, Chang Y et al. Benign prostatic hyperplasia specific health status measures in clinical research: How much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients? J Urol 1995;154:
Remzi M, Djavan B, Marberger M. Best of the 2002 AUA annual meeting. Rev Urol 2002;4(3):
McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349(25):
Data on file, MSD _________.
McConnell JD. The impact of medical therapy on the clinical progression of BPH. Presented at the Annual Meeting of the American Urological Association, Orlando, Florida, USA, May 2002.
NIDDK. Recent advances and emerging opportunities. Kidney, urologic, and hematologic diseases. Available at: Accessed May 14, 2003.
NIH. Two-drug therapy is best for symptomatic prostate enlargement: Combination should change clinical practice. May 28, 2002 [news release]. Available at: Accessed April 15, 2003.
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21. MTOPS: Medical Therapy Of Prostatic Symptoms
Before prescribing any of the products mentioned in this slide presentation, please consult the manufacturers’ prescribing information.
Before prescribing any of the products mentioned in this slide presentation, please consult the manufacturers’ prescribing information.
Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved PSC 2004-W SS Printed in USA
VISIT US ON THE WORLD WIDE WEB AT
Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved PSC 2004-W SS Printed in USA
VISIT US ON THE WORLD WIDE WEB AT
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