P&S Journal: Fall 1995, Vol.15, No.3
Clinical Advances: By Lynne Christensen
Less Invasive Treatments for Sexual Dysfunction
A reported 18 million American men between the ages of 40 and 70 experience some sexual dysfunction. Dr. Ridwan Shabsigh, assistant professor of urology and director of the Male Reproductive Center/Sexual Dysfunction Unit, believes this estimate is low. Many men do not seek assistance for their condition. Some don't know they have a problem; some know there's a problem, but don't realize treatment is available; some are too embarrassed to admit something's wrong; and some older men accept the myth that people stop having sexual activity as they age.
People can engage in sexual activity at all ages, and for men who experience erectile dysfunction (impotence) or ejaculation dysfunction (premature ejaculation), treatments are available and many new therapies are under development, including newer experimental therapies aimed at providing less invasive methods of overcoming dysfunction. Many men shy away from getting help for impotence because many of the therapies-such as penile prostheses, vacuum tumescence devices, and surgery-are so invasive.
Erectile dysfunction can be associated with psy-
chologic, neurologic, vascular, hormonal, or cavernosal disorders or with drugs and treatments of systemic diseases (such as prostate cancer). Dr. Shabsigh and his multidisciplinary team at CPMC and other sites are investigating methods to address sexual dysfunction that will target both physiologic and psychologic processes through less invasive delivery mechanisms.
Intracavernosal injection of local vasodilators, such as prostaglandin E1 (PGE1), is a common method of inducing an erection. Up until now PGE1 has been prescribed as an off-label use of the drug. In July, however, the FDA approved Upjohn's PGE1 for the indication of erectile dysfunction.
About 60 percent of men with erectile dysfunction are now treated with PGE1. The drug's approval for this indication is predicted to dramatically increase the number of patients who benefit. "This is the first time that a major pharmaceutical company will play a role in treatment for impotence." Dr. Shabsigh predicts this will increase awareness and, consequently, use.
CPMC is one site involved in the Medicated Urethral System for Erection (MUSE) trial to study
a novel delivery method for administering PGE1 into the penis. The drug is encapsulated in a small (1mm by 4mm) pellet delivered into the urethra via a preloaded inserter (a 1-inch blunt tube with a plunger) just before intercourse. The double-blind, placebo-controlled phase of the study is completed, and the open-label phase has begun. Potential side effects of PGE1 are pain, hypotension, and urinary burning.
While intra-urethral delivery is preferable to injections, oral delivery is even better. Early trials are under way to test an orally administered penile vasodilator accidentally discovered by a team of researchers in England trying to develop a coronary vasodilator. This phosphodiesterase inhibitor failed to work on coronary arteries, but researchers noticed it had a vasodilator effect selective to the penis (and to a lesser degree the eye muscles). The drug is in Phase II clinical trials and is expected to enter Phase III trials late in 1995 at CPMC and other centers. If the drug proves efficacious it could be a major breakthrough in treatment of impotence.
Novel therapies for sexual dysfunction are not restricted to treating organic causes. Dr. Shabsigh and his team have just finished a multicenter Phase II/III clinical trial of apomorphine, a dopamine agonist found to stimulate the sexual center in the brain. This drug treats psychogenic impotence in men who have fully intact organic function. Originally a veterinary medicine used for emesis, apomor-phine (a cousin of morphine) was found to cause erection when given to men in small doses. The drug is delivered sublingually because it is rapidly absorbed. Not surprisingly, potential side effects are nausea and vomiting.
"This is a true innovation because it is the first drug therapy for psychogenic impotence," says Dr. Shabsigh. Currently, the only therapy is counseling.
Premature ejaculation, another type of sexual dysfunction, is also getting attention from researchers. The candidate therapy is a drug that has received widespread attention as an antidepressant-Prozac, or fluoxetine. Researchers are taking one of the troublesome side effects of the drug, delayed ejaculation, and turning it into something positive. CPMC is involved in the planning stages of a multicenter study to test Prozac, a selective serotonin reuptake inhibitor, for this dysfunction.
"Once more diverse options for less invasive procedures become widely available, more men will benefit from treatment for sexual dysfunction, which will have a tremendous effect on the quality of their lives," says Dr. Shabsigh.
copyright ©, Columbia-Presbyterian Medical Center
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