Decrease in Effectiveness. Over time, PDE5 inhibitors may lose effectiveness. A 2001 study found that after two years, 20% of patients had increased their dose of sildenafil to achieve the same effect, and 17% had discontinued the drug due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that made their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for 2 to 3 years remained satisfied with the treatment. In addition, a study reported that sildenafil treatment may be less effective in men with diabetes.
Experimental Drugs
Other PDE5 Inhibitors. Avanafil and SLX-2101 are new PDE5 inhibitors that are showing promising results in clinical trials.
Melanocortin receptor agonists. Melanocortin receptor agonists work on the central nervous system instead of the vascular system. Bremelanotide (formerly PT-141) is the first of these drugs to be investigated in clinical trials. Researchers are testing the drug as a nasal spray given either alone or in combination with a PDE5 inhibitor.
Gene Therapy. Researchers are investigating gene transfer therapy as a possible cure for erectile dysfunction. Promising results from the first human trial were presented at the 2006 American Urological Association meeting. The gene-based therapy, called hMaxi-K, uses injections of a gene that helps the body manufacture proteins to improve smooth muscle relaxation. The treatment requires injections twice a year. It is still in the very early stages of research.
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