Radiation Or Trauma

5% NEUROLOGICAL CAUSES 3% ENDOCRINE PROBLEMS

1% OTHER

the next 25 years—ultimately affecting more than 330 million men worldwide.

If nerve stimuli cannot reach the penis for any reason, an erection problem is inevitable. Such dysfunction can also be an unfortunate complication of surgery to remove the prostate gland to treat prostate cancer, because this procedure can damage penile nerves. Diabetes can lead to nerve and blood vessel damage in the penis as well. Many neurological conditions—including spinal cord injury, Parkinson's disease, multiple sclerosis and stroke—can cause problems. And because a man's moods and mental well-being affect the flow of nerve messages to the penis, it is not surprising that stress, depression, anxiety or anger often underlies erection difficulties.

Using their growing knowledge of central nervous system control, researchers have begun to develop medications that target the central nervous system. A drug called apomorphine will most likely be the first in a new generation of therapies that acts directly on the brain as opposed to the penis, as Viagra does. Apomorphine—brand name Uprima— mimics the neurotransmitter dopamine, enhancing erections by binding to specific receptors on nerve cells in the para-ventricular nucleus and the MPOA, thereby turning on proerectile pathways.

Apomorphine is under review by the U.S. Food and Drug Administration for

ERECTILE DYSFUNCTION has many causes, ranging from stress and other psychological concerns to purely physiological factors. This chart depicts the main physical causes of dysfunction and reveals that vascular problems underlie a vast number of cases.

PROBABILITY

PROBABILITY

approval, and a final decision is expected soon. Although the compound has been used in medicine for more than a century—for the treatment of Parkinson's disease, among other disorders—it was not until the mid-1980s that investigators, including R. Taylor Segraves, a psychiatrist at Case Western Reserve University, and Jeremy P. W. Heaton, a urologist at Queen's University in Ontario, began investigating it for the treatment of erectile dysfunction. Since then, clinical studies have evaluated apomorphine in more than 3,000 men and found that it can successfully treat those with many different types of erectile dysfunction.

Like all drugs, apomorphine can cause unwanted side effects. Whereas Viagra, the most widely prescribed drug for erectile dysfunction, can give rise to headaches, nasal stuffiness and facial flushing, apomorphine can induce nausea during its initial use. In the future, we may be able to treat some men more effectively by combining apomorphine with therapies that act directly on the penis.

Sex and the Sexes

Until recently, most research on sexual function focused in large part on men and the control of penile erection. Fortunately, this is changing, as we increasingly recognize that sexual dysfunction is extremely common—and treatable—in both sexes. In fact, a recent survey of more than 3,000 Americans reported that the number of women with sexual complaints was greater than the number of men: 43 percent as opposed to 31 percent.

Many researchers are studying the mechanisms that control sexual function in women and are testing therapies to treat female sexual disorders. Our laboratory is conducting a clinical trial to determine whether apomorphine can enhance sexual arousal in women with such problems. We also are testing a new FDA-approved device called the EROS-Clitoral Therapy Device, which is used to provide gentle suction to the clitoris, causing engorgement. In women with sexual dysfunction, it has been shown to safely improve sexual sensation, lubrication, orgasm and sexual satisfaction.

This research has made us aware of some similarities between the sexes in the central nervous system's control of arousal, orgasm and various sexual functions. Preliminary evidence suggests that the central control of sexual function in men and women is remarkably similar. For instance, as noted earlier, both sexes experience nocturnal arousal responses, and both are vulnerable to SSRI-induced sexual dysfunction.

Of course, there are also dramatic differences—as in the postorgasmic refractory period, the normal delay after an orgasm before arousal can occur again. Women can have multiple orgasms and therefore have virtually no refractory period, but most men have a refractory period that lasts from several minutes to many hours.

IMPOTENCE increases with age, according to several surveys. In 25 years, given the aging of the world's population, it is estimated that the condition may affect more than 330 million men.

We have come a long way since da CE Vinci's discovery that the penis fills with 5 blood—not air or spiritual essences— URIA during an erection. The past decade has L revolutionized not only the field of erection research but also our societal attitudes about sexual health. Only a few years ago erectile dysfunction went generally untreated.

Today this condition and other sexual problems are more openly recognized and discussed. Millions of men are receiving care for erection troubles, thanks to a burgeoning appreciation of the importance of sexual health and the availability of more effective and convenient treatments. In the near future we anticipate that there will be an even wider array of therapies for men and women. With our increasing insight into the brain's role in controlling our sexuality, we are also moving toward a more holistic view of sexual well-being—one that integrates mind and body and responds to the unique needs of both sexes. E3

The Authors

IRWIN GOLDSTEIN is a urologist at Boston University. He is a member of the Working Group for the Study of Central Mechanisms in Erectile Dysfunction, which was formed in 1998. The other members are John Bancroft of Indiana University; François Giuliano of the Faculté de Médecine, Université Paris-Sud; Jeremy P. W. Heaton of Queen's University, Ontario; Ronald W. Lewis of the Medical College of Georgia; Tom F. Lue of the University of California, San Francisco; Kevin E. McKenna of Northwestern University; Harin Padma-Nathan of the University of Southern California; Raymond Rosen of the Robert Wood Johnson Medical School; Benjamin D. Sachs of the University of Connecticut; R. Taylor Segraves of Case Western Reserve University; and William D. Steers of the University of Virginia. All the authors consult or investigate (or have done so in the past) for one or more pharmaceutical companies—among them Abbott, Eli Lilly, Merck, Pfizer and TAP; Sachs owns stock in Abbott; Heaton shares several patents on apomorphine.

Further Information

Impotence and Its Medical and Psychological Correlates: Results of the Massachusetts Male Aging Study. H. A. Feldman et al. in Journal of Urology, Vol. 151, No. 1, pages 54-61; January 1994.

Neural Control of Penile Erection. F. Giuliano, O. Rampin, G. Benoit and A. Jardin in Urology Clinics of North America, Vol. 22, No. 4, pages 747-766; November 1995. The Brain Is the Master Organ in Sexual Function: Central Nervous System Control of Male and Female Sexual Function. K. McKenna in International Journal of Impotence Research, Vol. 11, Supplement 1, pages 548-555; 1999. Sexual Dysfunction in the United States: Prevalence and Predictors. E. O. Laumann, A. Paik and R. C. Rosen in Journal of the American Medical Association, Vol. 281, No. 6, pages 537-544; February 10, 1999.

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