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Biomedical subjects

Steven A Kaplan

Publications and source records attributed to Steven A Kaplan.

At least 19 recordsLinked to original sources
PubMed2006

Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial.

CONTEXT: Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists. OBJECTIVE: To evaluate the efficacy and safety of tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006. INTERVENTIONS: Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks. MAIN OUTCOME MEASURES: Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed. RESULTS: A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%). CONCLUSIONS: These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.

Adrenergic alpha-Antagonists↗
PubMed2006

First-line treatment for symptomatic benign prostatic hyperplasia: is there a particular patient profile for a particular treatment?

When the range of treatment options for benign prostatic hyperplasia (BPH) is as broad as the BPH spectrum of symptoms, how should urologists and their patients choose the best initial treatment? Treatment goals should include reducing both lower urinary tract symptoms and relieving associated morbidities, such as urinary retention, persistent gross hematuria, recurrent infections, bladder stones, or renal insufficiency-which are all indications for surgery. However, if one views BPH as a chronic and progressive disease, should a primary goal of BPH management be the prevention of the BPH-associated morbidities? The goal of this paper is to provide a literature update regarding various treatment options in the setting of initial treatment for symptomatic BPH. Novel approaches to BPH management are discussed. In all cases, the risks and benefits of each treatment need to be considered and discussed with the patient; the decision is ultimately up to the patient and his urologist.

Humans↗
PubMed2006

The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men?

PURPOSE: We examined pooled baseline data from 2 lipid treatment studies to evaluate the relationship among total serum testosterone levels, obesity and the metabolic syndrome in aging men. MATERIALS AND METHODS: Baseline total serum testosterone, lipid, glycemic and anthropometric data were obtained from 864 men (mean age 52 years) participating in 2 lipid treatment studies. Inclusion criteria for the 2 studies included low-density lipoprotein cholesterol 130 to 160 mg/dl and triglycerides 350 mg/dl or less. RESULTS: For all patients as well as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone decreased with increasing body mass index (p < 0.0001 for Pearson correlation coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in obese and severely obese aging men with the metabolic syndrome were around 150 and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic syndrome. The relative contributions of each of the individual National Cholesterol Education Program Adult Treatment Panel III components of the metabolic syndrome to low serum testosterone in aging men was examined using multiple linear regression modeling. Based on these analyses the presence of diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m or greater, and triglycerides 150 mg/dl or greater each appeared to have a clinically relevant association with low serum testosterone. CONCLUSIONS: This study demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men. These data suggest that the well established association between erectile dysfunction and pre-diabetes/diabetes (particularly in obese pre-diabetic/diabetic patients) may involve a hormonal component.

Age Factors↗
PubMed2006

Hemodynamic interaction study between the alpha1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects.

OBJECTIVES: To examine the hemodynamic interactions of the phosphodiesterase type 5 (PDE-5) inhibitor tadalafil with the uroselective alpha1-blocker alfuzosin (10 mg daily), commonly prescribed for benign prostatic hyperplasia-related lower urinary tract symptoms. Erectile dysfunction is commonly associated with lower urinary tract symptoms. PDE-5 inhibitors are the first-line treatment of choice for erectile dysfunction. When co-administered with alpha1-blockers, PDE-5 inhibitors could induce orthostatic hypotension. METHODS: During each of the two periods of a randomized, double-blind, placebo-controlled, crossover study, 18 healthy middle-aged men received alfuzosin 10 mg daily for 7 days and either a single 20-mg dose of tadalafil or placebo on day 7. The blood pressure and heart rate were monitored before and for 24 hours after tadalafil or placebo. RESULTS: The combination of tadalafil 20 mg with alfuzosin 10 mg daily elicited a maximal decrease in standing systolic blood pressure that was not significantly different from that after placebo (mean difference 4.35 mm Hg, P = nonsignificant). Analysis of the blood pressure outliers showed that only 1 subject had an asymptomatic standing systolic blood pressure of less than 85 mm Hg. No vasodilatory adverse events were observed with the combined medication. CONCLUSIONS: In healthy, middle-aged men, tadalafil 20 mg showed no clinically relevant hemodynamic interactions with alfuzosin 10 mg daily.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia.

OBJECTIVES: To evaluate the efficacy and safety of nighttime dosing with tolterodine extended release (TER) in men with overactive bladder (OAB) and nocturia. METHODS: This was a post hoc analysis of data from two 12-week, double-blind, placebo-controlled trials of nighttime (<4 hours before bedtime) TER (4 mg daily) dosing. Men with a mean micturition frequency of eight or more times in 24 hours, including a mean of 2.5 or more nocturia episodes/night, were included. For each micturition, patients used 7-day diaries to record urinary urgency on a 5-point urgency rating scale (1, none; 2, mild; 3, moderate; 4, severe; 5, urgency urinary incontinence). Micturitions were analyzed post hoc by urgency rating categories: total (1 to 5), non-OAB (1 to 2), OAB (3 to 5), and severe OAB (4 to 5). Adverse events were recorded throughout the study. RESULTS: A total of 745 men (mean age 64 years) were randomized to placebo (n = 374) or TER (n = 371). Of the 745 men, 73% reported no incontinence episodes in a 7-day diary at baseline. At week 12, the weekly values for nighttime severe OAB micturitions and 24-hour and daytime total, OAB, and severe OAB micturitions were significantly reduced in the TER group versus the placebo group. The TER-treated men also reported a significant reduction in the mean urgency rating versus placebo. Adverse events associated with TER were low and comparable to those in the placebo group, with the exception of dry mouth (11% versus 4%). Withdrawals because of adverse events were infrequent (3% TER, 4% placebo). Five men were withdrawn for symptoms suggestive of urinary retention (3 TER, 2 placebo). CONCLUSIONS: Nighttime TER dosing reduced urgency-related micturitions and was well tolerated in men with OAB and nocturia.

Benzhydryl Compounds↗
PubMed2006

Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater.

PURPOSE: We examined data from the Medical Therapy of Prostatic Symptoms trial to determine the relationship between baseline TPV and the effect of medical therapy in men with LUTS secondary to BPH. MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to placebo, 4 to 8 mg doxazosin, 5 mg finasteride or the combination of doxazosin and finasteride. Average treatment duration was 4.5 years The primary outcome was time to overall clinical progression of BPH, defined as a confirmed 4 point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency or recurrent urinary tract infection. Secondary outcomes were the need for invasive therapy for BPH, and changes in AUA SS and the maximum urinary flow rate with time. TPV was measured by transrectal ultrasound at baseline and study end. RESULTS: In patients with a small prostate (baseline TPV less than 25 ml) combination therapy was no better than doxazosin alone for decreasing the risk of clinical progression of BPH and need for invasive therapy as well as improving AUA SS and the maximum urinary flow rate. However, in patients with moderate size (25 to less than 40 ml) or enlarged (40 ml or greater) glands combination therapy led to a clinical benefit in these outcomes that was superior to that of doxazosin or finasteride. CONCLUSIONS: Combination therapy with doxazosin and finasteride led to a greater decrease in the risk of clinical progression of BPH than either drug alone in patients with LUTS with a baseline TPV of 25 ml or greater.

Aged↗
PubMed2006

Beneficial effects of extended-release doxazosin and doxazosin standard on sexual health.

The prevalence of benign prostatic hypertrophy (BPH) and erectile dysfunction (ED) both increase with age, and increasing evidence suggests a common cause rather than independent age-related changes. Arterial hypertension often accompanies these urological disorders, suggesting the possibility that increased alpha-adrenoceptor activity may be causal in all three conditions. As evidence for this model, alpha-adrenoceptor antagonists such as doxazosin produce therapeutically beneficial effects in lowering blood pressure, reducing prostate growth and BPH symptoms, and relieving ED. At postjunctional alpha(1)-receptors in the corpus cavernosa, noradrenaline causes vascular smooth muscle cell contraction, restricting blood flow, resulting in penile detumescence. Just as alpha-adrenoceptor antagonism results in systemic vasorelaxation to lower blood pressure, the same mechanism in the penis modulates the effects of noradrenaline to favour vasodilatation, resulting in improved erectile function. Increasing clinical evidence attests to the effectiveness of doxazosin in relieving ED, even in patients refractory to ED-specific treatment, as well as in reducing BPH symptoms and elevated blood pressure.

Adrenergic alpha-Antagonists↗
PubMed2006

Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence.

UNLABELLED: A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization. CONCLUSION: In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.

Adolescent↗
PubMed2006

Tadalafil for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

This article reviews the pharmacological properties of tadalafil and the current evidence supporting its use for treating symptomatic benign prostatic hyperplasia (BPH). The rationale for using tadalafil for BPH stems from the following three observations: first, the prevalence of lower urinary tract symptoms (LUTS), BPH and erectile dysfunction (ED) increases with age; second, phosphodiesterase-5 (PDE5) inhibition mediates smooth muscle relaxation in the lower urinary tract; and third, early clinical evidence demonstrates that PDE5 inhibitors such as tadalafil are successful in treating LUTS and ED. A shared pathophysiology makes PDE5 a promising target to treat both LUTS and ED. A recent randomised, controlled Phase II trial of tadalafil versus placebo for the treatment of symptomatic BPH revealed that tadalafil dosed once daily was well tolerated and demonstrated statistically significant and clinically meaningful efficacy in the treatment of LUTS secondary to BPH and improved erectile function in men with both LUTS and ED. The ability to treat both BPH and ED with one medication is noteworthy given the significant negative impact in quality-of-life measures these disorders have in ageing men. Careful patient selection and further trials are warranted.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Medical therapy for benign prostatic hyperplasia: new terminology, new concepts, better choices.

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted.

Journal Article↗
PubMed2006

Expanding the role of photoselective vaporization of the prostate.

The use of the potassium-titanyl-phosphate (KTP) laser for the ablative treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) has gained wide acceptance in the urologic community. The efficacy and safety of photoselective vaporization of the prostate using 60-W or 80-W KTP have been demonstrated in multiple trials, with significant impact on special high-risk surgical populations (ie, patients with large prostates and anticoagulated patients with multiple comorbidities) with symptomatic BPH. The high-power KTP laser technique has also shown encouraging results in the management of urethral strictures. With catheter removal, improvement in voiding may not immediately occur; however, with the efficient vaporization and limited coagulation necrosis that are routinely noted with high-power KTP applications, improvement may occur in as early as a few days to 1 week. Because of the superior surgical hemostasis associated with laser prostatectomy, no restrictions on physical activity are required after the procedure, even in the immediate postoperative period.

Journal Article↗
PubMed2006

Update on the american urological association guidelines for the treatment of benign prostatic hyperplasia.

The updated 2003 American Urological Association (AUA) Guidelines for the treatment of benign prostatic hyperplasia (BPH) are the culmination of an exhaustive effort predicated on scientifically accepted methods of reviewing the medical literature. In this second publication of the guidelines, a multidisciplinary panel reviewed a new meta-analysis of outcome data from the BPH literature from before and after 1994. The major differences between the 2 guidelines are the changes in our understanding of the biology of the prostate and the introduction of new therapies. The vast majority of randomized controlled trials, particularly with respect to minimally invasive therapies and progression of BPH, were performed after the release of the 1994 guidelines. Also, the most recent AUA panel carefully reviewed unpublished data to make the guidelines as timely as possible. Studies that were subsequently published included those on the value of combination medical therapy for BPH. The panel agreed on updated recommendations for the treatment of moderate-to-severe lower urinary tract symptoms associated with BPH, and diagnostic algorithms were revised. The durability and utility of the present guidelines should exceed that of its predecessor.

Journal Article↗