American Urological Association (AUA) 2011 Annual Meeting
May 14-19, 2011; Washington, DC
No Increase in Dizziness With Concomitant Use of Tadalafil and an Alpha-Blocker in Men With Benign Prostatic Hyperplasia
Washington, DC—A US team of researchers found that adding the drug tadalafil to an α1-adrenergic antagonist (α-blocker) as a therapeutic regimen for benign prostatic hyperplasia (BPH) did not significantly increase men’s likelihood of dizziness compared with use of an α-blocker alone. As the researchers explained in their podium session, which took place at the recent AUA annual meeting, patients with moderate-to-severe symptoms of BPH are typically treated with an α-blocker, but several studies have been investigating the safety and efficacy of concomitant use of tadalafil, which is an inhibitor of phosphodiesterase type 5. Tadalafil is currently approved by the US Food and Drug Administration as a treatment for erectile dysfunction and to improve lung blood flow in individuals with pulmonary arterial hypertension.
The investigators enrolled men age ≥45 years (mean age, 67 years; 90% white) with lower urinary tract symptoms caused by BPH. The patients were already taking an α-blocker at enrollment, and a 4-week washout period was instituted at the start of the trial to clear any other medications disallowed by protocol from their system. This was followed by 2 weeks of placebo, after which patients were randomized to tadalafil 5 mg (n = 158) or placebo (n = 160), administered daily for 12 weeks. After randomization, at least 20% of the patients in each cohort were ≥75 years of age and ≥20% in each group were taking a nonselective α-blocker.
The primary end point of the study was the proportion of men per study arm who experienced treatment-emergent dizziness. Efficacy, as indicated by change from baseline in International Prostate Symptom Score (IPSS); orthostatic vital signs; and general safety were secondary end points. Orthostatic hypotension was considered experiencing one or more of the following when going from a supine to standing position: a decrease in systolic blood pressure of ≥20 mm Hg; a decrease in diastolic blood pressure of ≥10 mm Hg; an increase in heart rate of ≥20 beats per minute; or an inability to remain standing during the assessment.
In an oral presentation, author Evan Goldfischer, MD, Hudson Valley Urology, Poughkeepsie, NY, reported no statistically significant difference in the rates of treatment-emergent dizziness between the groups. In the placebo arm, 9 (5.7%) patients experienced dizziness compared with 11 (7.0%) in the tadalafil group. A comparison of change in IPSS scores from baseline for the two cohorts also found no significant difference. Each group had a similar proportion of patients (30 per arm) who tested positive for at least one of the four indicators of treatment-emergent orthostatic hypotension.
Treatment-related adverse effects were described as primarily mild or moderate in severity. “The adverse event profile of concomitant tadalafil and α-blocker therapy was consistent with that of past studies of tadalafil monotherapy in men with benign prostatic hyperplasia,” said Goldfischer, speaking at the meeting. “Overall, no effect on treatment-emergent dizziness or other hemodynamic signs and symptoms was observed with tadalafil versus placebo administered with an α-blocker,” he concluded.
Rates of Prostate-Specific Antigen Testing Among Elderly Patients Remain High Despite Concerns About Necessity
Washington, DC—An examination of the annual rates of prostate-specific antigen (PSA) testing administered by primary care providers (PCPs) in the United States from 1997 through 2008 found that the rate of PSA testing more than doubled for men age ≥40 years and that many men age ≥75 years continue to be tested despite mounting evidence that they are unlikely to benefit from prostate cancer therapy. The study was presented during a podium session at the recent AUA annual meeting. Lead author Sandip Prasad, MD, Urologic Oncology Research Fellow, University of Chicago Medical Center, IL, discussed the data and their implications with Clinical Geriatrics.
To determine the frequency of PSA testing among men age ≥40 years, the authors used data from the National Ambulatory Medical Care Survey for the years 1997 through 2008. They limited the study to men without prostate cancer, most of whom received testing at a primary care visit.
In 1997, approximately 5.3 million PSA tests were administered at 5.7% of PCP visits. More than twice as many PSA tests were performed in 2008, with an estimated 12.4 million tests administered at 11.5% of office visits. This indicated an annual increase of nearly 6.5% (P <.01), a finding that surprised the authors.
“Given that prostate cancer incidence declined during our study period and that multiple organizations issued recommendations against routine PSA screening between 1997 and 2008, we [had] expected to find that both PCPs and urologists would have lower rates of PSA test utilization,” Prasad explained.
Although the proportion of PSA tests administered by urologists was not provided in the study abstract, Prasad said that testing rates were “essentially identical” between urologists and PCPs. In addition, both PCPs and urologists were significantly more likely to give PSA tests to non-Hispanic (black and non-Hispanic white) men than to Hispanic men (P = .01 and P = .04, respectively). “This may reflect practice patterns or perceptions regarding the higher rates of prostate cancer incidence and mortality in non-Hispanic men,” he said.
Men ages 40 to 49 years were least likely to undergo PSA testing, which was carried out at 5.1% of PCP visits. This compared with 9.6% of visits for men ages 50 to 59 years, 11.0% for men ages 60 to 69 years, 8.5% for men ages 70 to 74 years, 6.9% for men ages 75 to 85 years, and 5.3% for men age >85 years.
In the study’s latter years, data and guidelines started to emerge that questioned the value of PSA testing for men ≥75 years. Despite this, Prasad said that the study team did not see a decline in testing for this demographic. “In fact, it continued to increase,” he noted. Individuals with Medicare and Medicaid were less likely than those with private insurance to undergo PSA testing at the primary care office. Findings were consistent across all geographic regions. Nor was an association identified between any comorbidity and the likelihood of undergoing PSA screening.
Prasad said that the relationships between PSA screening rates, prostate cancer incidence, and prostate cancer deaths are not clear. Whereas one might expect that an increase in PSA screening would correlate with more diagnoses of prostate cancer, he pointed out that prostate cancer diagnoses had actually declined during the study period. Prasad proposed several factors that might account for this discordance, including the possibility of a decrease in biopsy rates due to demographic or clinical elements; fewer men undergoing invasive digital rectal examinations, a procedure that can also suggest the need for a biopsy; and a “culling effect” that occurs when men with suspicious PSA levels are found to have prostate cancer on biopsy and are then removed from the PSA screening pool, thus reducing the likelihood that repeated PSA screening among the remaining men will result in a diagnosis of prostate cancer.
The study has important implications for clinicians who treat geriatric patients. “PSA testing continues to be performed at unnecessarily high rates in older men with limited life expectancy, who are least likely to benefit from screening efforts,” said Prasad. He cautioned against using “age alone…as a surrogate for life-expectancy,” however. “Geriatric patients [should] be assessed for concomitant comorbidities so that those individuals with greater than 10-year life expectancy are offered screening.”
Topical Estrogen Cream Provides Symptom Relief and Improved Quality of Life for Postmenopausal Women With Urinary Incontinence
Washington, DC—Although the use of estrogen replacement therapy has been recommended by many experts as a treatment for urinary incontinence (UI) in postmenopausal women, its role in the management of UI remains controversial. Among its purported benefits, estrogen therapy has demonstrated an ability to restore local vascularity and normal vaginal microbiology, improve mucosal coaptation, enhance alpha-adrenergic receptor sensitivity, prevent bladder contractions, delay bladder sensations of urgency, and increase urethral tone and resistance to outflow.
At the recent AUA annual meeting, Alexander DeHaan, DO, and colleagues from Grand Rapids, MI, shared the findings of a study investigating the effects of topical estrogen cream on UI symptoms. They said that the consistent application of a topical estrogen cream reduced symptoms of urinary tract infections (UTIs), stress-related UI, and atrophic vaginitis (the inflammation of the vagina due to thinning tissue and decreased lubrication) in postmenopausal women. The data were presented during a moderated poster session titled Assessing the Efficacy of Topical Estrogen Cream in Post-Menopausal Women With Urinary Incontinence.
Researchers reviewed data for 40 postmenopausal women ages 46 to 84 years (mean age, 62 years) with a chief complaint of UI. Data were gathered from each patient using four validated questionnaires: the Incontinence Quality of Life (I-QOL) Questionnaire, the International Consultation on Incontinence Questionnaire Short Form, the Urogenital Distress Inventory-6, and the Incontinence Impact Questionnaire-7. Patients were asked to describe their urinary symptoms before the use of topical estrogen cream and again after 3 months of treatment.
Before topical estrogen use, 67.5% of patients (n = 27) experienced atrophic vaginitis, 35% (n = 14) had symptoms of UTI, and 87.5% (n = 35) experienced stress-related UI. After treatment, 32.5% of patients (n = 13) had symptoms of atrophic vaginitis (P <.0005), 10% (n = 4) had symptoms of UTI (P <.002), and 30% (n = 12) reported stress-related UI (P <.0001). The study also found that all measured variables in each validated questionnaire demonstrated statistically significant reductions in events after treatment. A dramatic rise in the I-QOL was reported; prior to treatment, patients rated their feelings regarding their urinary condition an average of 2.45 on a scale of 0 (terrible) to 10 (pleased). Following treatment, the mean assessment was 8.0, representing a significant improvement (P <.00008).
The authors concluded in the poster, “Post-menopausal women who suffer from lower urinary tract symptoms including urinary incontinence, can gain a dramatic improvement in their overall quality of life as well as a reduction in symptoms from vaginal atrophy and urinary symptoms including incontinence when using a consistently applied dose of topical estrogen cream.”
“In elderly patients with UTIs or bothersome urinary symptoms in the absence of infection, topical estrogens (creams, pellets, or rings) can be used safely in the long-term for relief of symptoms,” said Diane Bigham, DO, one of the lead researchers of the study, in an interview with Clinical Geriatrics.
“It would be nice to see widespread use of topical estrogens as first-line therapy for all estrogen-deficient patients, regardless of age, for their bothersome urinary symptoms,” Bigham said. “Unfortunately, the majority of the data reflects oral estrogen use and its negative effect on urinary symptoms and incontinence, so the dramatic effects of topicals are underrated, underreported, and, therefore, underused.”