Tom F. Lue

BACKGROUND: Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [corrected] in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes. METHODS: In a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question. RESULTS: In the dose-response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were <0.001). For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as compared with 22 percent for those receiving placebo (P<0.001). The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo (P<0.001). Headache, flushing, and dyspepsia were the most common adverse effects in the dose-escalation study, occurring in 6 percent to 18 percent of the men. Ninety-two percent of the men completed the 32-week extension study. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.

Stress urinary incontinence (SUI) is one of the pelvic floor disorders affecting tens of million of women worldwide. In general, non-surgical options have relatively limited efficacy. The most effective treatment is mid-urethral sling surgery which carries substantial risks of perioperative and postoperative complications. Regenerative therapy with the injection of several types of stem cells and stem cell products is promising but further investigation is needed before clinical implementation can be considered. In recent years, the application of microenergy therapy as a non-invasive treatment for SUI has received increasing attention. Preclinical animal studies of these models have demonstrated that low-intensity extracorporeal shockwave therapy (Li-ESWT) and microenergy acoustic pulse (MAP) therapy are capable of regenerating urethral sphincter tissue and pelvic floor muscles leading to improved urinary continence. One pilot clinical trial with Li-ESWT also reported improved quality of life in women with SUI as well as the symptoms. The objective of this review is to summarize the potential mechanisms associated with Li-ESWT and MAP therapies of SUI: (I) activation of tissue-resident stem cells; (II) regeneration of musculature in the urethra and pelvic floor; (III) improvement in biomechanical property of pelvic floor muscles; (IV) modulation of cellular signaling pathways. Further studies of the molecular mechanisms, optimal treatment dosage and schedule, and potential long-term side effects are needed to provide this non-invasive regenerative therapy for millions of women with SUI.