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Volume 9, Number 4

Review Articles

Estrogenic Side Effects of Androgen Deprivation Therapy

Treatment Update

Celestia Higano Matthew R Smith Michael G Oefelein Theresa A Guise James A Eastham Michael S Cookson

Androgen deprivation therapy (ADT) is part of standard therapy for locally advanced or metastatic prostate cancer and is frequently used in men with a rising prostate-specific antigen following radical prostatectomy or radiation therapy. In some men, ADT may be administered for years or even decades. The intended therapeutic effect of ADT is testosterone deficiency. Because estrogen is a normal metabolite of testosterone, ADT also results in estrogen deficiency. ADT has a variety of adverse effects, many of which are primarily related to estrogen deficiency. Bone mineral density may decrease by 4% to 13% per year in men receiving ADT. The fracture rate for patients on ADT averages 5% to 8% per year of therapy. Hot flashes, gynecomastia, and breast tenderness are common side effects associated with ADT. In the clinic, minimum baseline testing should include weight measurement, blood pressure reading, and fasting lipid panel and serum glucose tests. Currently, there are no large outcome trials in men on ADT testing the available therapies for adverse effects. No therapies are specifically approved for treatment of adverse effects in men on ADT. Although some therapies can be used for a single indication (based upon small studies), there is currently no agent to treat the multiple estrogenic side effects of ADT. [Rev Urol. 2007;9(4):163-180]

Androgen deprivation therapy Cardiovascular disease Gynecomastia Osteoporosis fracture Male hot flashes

Review Articles

Alpha Blockers for the Treatment of Benign Prostatic Hyperplasia

Treatment Update

The evolution of alpha blocker therapy for benign prostatic hyperplasia (BPH) has focused on improving convenience and tolerability. Indications for treating BPH include reversing signs and symptoms or preventing progression of the disease. The indication that most commonly drives the need for intervention is relief of lower urinary tract symptoms (LUTS) with the intent of improving quality of life. Alpha blockers are the most effective, least costly, and best tolerated of the drugs for relieving LUTS. Four long-acting alpha 1 blockers are approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, and alfuzosin. All are well tolerated and have comparable dose-dependent effectiveness. Tamsulosin and alfuzosin SR do not require dose titration. Alfuzosin, terazosin, and doxazosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. [Rev Urol. 2007;9(4):181-190]

Benign prostatic hyperplasia Lower urinary tract symptoms Quality of life Tamsulosin Alfuzosin Doxazosin Terazosin

Review Articles

Anticholinergics and Central Nervous System Effects: Are We Confused?

Treatment Update

Edward Zoltan David R Staskin

The central nervous system (CNS) effects of anticholinergic agents have been documented in various patient populations and to varying degrees in case reports, brain-activity surrogates, and computerized cognitive testing. The older patient population with overactive bladder represents a group at increased risk of cognitive impairment and other CNS side effects associated with antimuscarinic agents. The complexity of the effect of anticholinergic agents on CNS function requires an increased level of careful investigation. Studies need to be performed in the at-risk population with multiple, validated tests at clinically prescribed doses in acute and chronic situations. These studies need to take into account the effect of commonly prescribed dosing regimens, with doses selected to represent with equivalent bladder potency. The alterations in the serum levels and parent/metabolite effects contributed by metabolic issues or drug delivery systems require special attention. [Rev Urol. 2007;9(4):191-196]

Overactive bladder Elderly Antimuscarinic drugs CNS adverse events Cognitive impairment

Review Articles

Extending the Rationale of Combination Therapy to Unresponsive Erectile Dysfunction

Treatment Update

Christopher Reece Diedre Nienow Ajay Nehra Rajeev Kumar

Combination therapies aim to overcome the limitations of individual drugs by selecting diverse targets of action to enhance effectiveness synergistically. This article reviews the principles of combination therapy and its applications for benign prostatic hyperplasia and overactive bladder. It then examines pathophysiological, pharmacological, and clinical evidence for currently available drug and device combinations for erectile dysfunction that has not responded to first-line, single-agent therapy. [Rev Urol. 2007;9(4):197-206]

Benign prostatic hyperplasia Overactive bladder Erectile dysfunction Combination therapy Intracavernosal therapy Intraurethral therapy

Review Articles

Newer Potential Biomarkers in Prostate Cancer

Diagnostic Update

Jonathan L Wright Paul H Lange

Prostate-specific antigen (PSA) screening has led to a significant rise in the number of men diagnosed with prostate cancer and an associated increase in biopsies performed. Despite its limitations, including a positive predictive value of only 25%-40%, PSA remains the only generally accepted biomarker for prostate cancer. There is a need for better tools to not only identify men with prostate cancer, but also to recognize those with potentially lethal disease who will benefit from intervention. A great deal of work has been done worldwide to improve our knowledge of the genetics behind prostate cancer and the specificity of PSA by developing assays for different PSA isoforms. Common genetic alterations in prostate cancer patients have been identified, including CpG hypermethylation of GSPT1 and TMPRSS2:ERG gene fusion. Serum and urine detection of RNA biomarkers (eg, PCA3) and prostate cancer tissue protein antibodies (eg, EPCA) are being evaluated for detection and prognostic tools. This article reviews some of the promising developments in biomarkers. [Rev Urol. 2007;9(4):207-213]

Prostate-specific antigen PCA3 Alpha-methylacyl-CoA racemase Autoantibody arrays Epigenetic markers Gene fusion proteins Human kallikreins PSA isoforms RNA biomarkers

Meeting Reviews

New Findings in Bladder and Prostate Cancer

Meeting Review

Maximilian Rom Franklin E Kuehhas Bob Djavan

Highlights of the 22nd Annual Congress of the European Association of Urology, March 21-24, 2007, Berlin, Germany [Rev Urol. 2007;9(4):214-219]

Prostate cancer Bladder cancer Transitional cell carcinoma Prostate biopsy Human kallikrein Urothelial tumors Laparoscopic radical prostatectomy

Bilateral Testicular Infarction and Orchiectomy as a Complication of Polyarteritis Nodosa

Case Review

Sean P Stroup Shannon R Herrera Donald S Crain

We report an unusual case of a 28-year-old male with constitutional symptoms and bilateral testicular pain. After diagnosis of cytomegalovirus (CMV) hepatitis, his constitutional symptoms and testicular pain worsened despite treatment for epididymoorchitis. Ultrasound was concerning for infarction. Exploration in the operating room revealed bilateral testicular infarction requiring bilateral orchiectomy with subsequent androgen hormone replacement. Pathologic diagnosis was polyarteritis nodosa (PAN). PAN is a rare systemic vasculitis that affects multiple organs. There are no previous reports of PAN-induced vasculitis leading to bilateral testicular infarction and bilateral orchiectomy. [Rev Urol. 2007;9(4):235-238]

Testicular infarction Polyarteritis nodosa Androgen replacement therapy

Literature Reviews

T1 Bladder Cancer

Reviewing the Literature

Shahrokh F Shariat

Literature Reviews

Reviewing the Literature

Frank Costa Michael B Chancellor

Literature Reviews

Prostate Cancer

Reviewing the Literature

Danil V Makarov Alan W Partin