Sheldon Freedman | PubMed Health

PubMed2004

Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.

OBJECTIVES: To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-alpha-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms. METHODS: Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL. RESULTS: A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (-26.2%), American Urological Association Symptom Index (-6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (-20.7%), American Urological Association Symptom Index (-5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends. CONCLUSIONS: Dual inhibition of 5-alpha-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.

5-alpha Reductase Inhibitors↗

PubMed2002

Sacral neuromodulation as an effective treatment for refractory pelvic floor dysfunction.

OBJECTIVES: To determine the long-term efficacy and complications of sacral nerve stimulation as an alternative therapy for pelvic floor dysfunction. Pelvic floor dysfunction is a complex problem that can be refractory to current treatment modalities. Conservative therapy rarely results in a durable cure of patients, and various surgical procedures have significant side effects and less than optimal results. METHODS: Sixty-four patients, 54 women and 10 men, with various forms of voiding dysfunction for whom other forms of therapy had failed underwent placement of the Medtronic Implantable Pulse Generator sacral nerve implant. The mean age was 47 years. The presenting complaint was frequency, urgency, and urge incontinence in 44 patients and chronic nonobstructive urinary retention requiring self-catheterization in 20 patients. Forty-one patients also had chronic pelvic and perineal pain associated with their voiding symptoms. The mean duration of symptoms was 69 months. All patients underwent percutaneous nerve evaluation before the permanent implant and demonstrated more than 50% improvement in their symptoms. All patients were evaluated at 1, 3, 6, 12, and 24 months, and yearly thereafter. The assessment of the voiding symptoms was done both subjectively by patient symptoms and objectively using voiding diaries recorded for 3 days. A validated verbal rating pain scale was used to evaluate pain levels. RESULTS: Eighty percent of the patients had 50% or greater improvement in their presenting symptoms and quality of life after the procedure, with a mean follow-up of 24 months. Patients with frequency-urgency showed a reduction in the number of voids per day with a significant increase in voided volumes. Patients with urge incontinence showed a reduction in leaking episodes from 6.4 to 2.0/24 hr, with a decrease in the number of pads used from 3.5 to 1.2/day. Sixteen of 20 patients with urinary retention were able to void with a residual volume of less than 100 mL. Patients with chronic pelvic pain showed a decrease in the severity of pain from a score of 5.8 to 3.7. Complications were minimal and encountered in 18.7% of the patients. CONCLUSIONS: Sacral nerve stimulation is an effective and durable new approach to pelvic floor dysfunction with minimal complications. Test stimulation provides a valuable tool for patient selection.

Adult↗