That largely masculine roar emitted by cheering football fans may well resound for a new drug now in clinical trials. Pfizer Pharmaceuticals is counting on it to give a lift to millions of men. Sildenafil is an oral therapy for what used to be called impotence - now known as erectile dysfunction - a problem affecting between 18 and 30 million men in the United States and an estimated 140 million worldwide.
To understand why the drug merits such a rousing reception, you need to know that a current best therapy is a self-administered injection into the penis prior to intercourse.
According to Raymond Rosen, PhD, professor of psychiatry at UMDNJ-Robert Wood Johnson Medical School, the injectables do work, but they have major drawbacks and side effects. In a minority of users they cause scarring and plaque buildup, and can also result in priapism - prolonged erections that can be damaging. About 50 percent of men stop using them after a year, complaining that the shots are unpleasant and a turnoff. "Most men ask, 'Isn't there a pill I can take?'" reports Rosen.
Soon there may be. Sildenafil - now in Phase III clinical trials - is viewed as a breakthrough drug by many. Rosen, who is directing one of the trials at the medical school, says the medicine looks very promising and will be available in 1998.
Meanwhile the business side of sexual dysfunction is booming. In the past, embarrassment and a paucity of effective remedies dissuaded many men from seeking help. It's only in the last 15 years that specialists have understood the physiology of an erection, and the new knowledge is revolutionizing treatment.
Sexual dysfunction - defined as the consistent inability to have an erection sufficient for intercourse - was thought to be psychological, except in situations of obvious injury and paralysis. Now specialists say that 70 to 90 percent of cases are physical in origin, and that is the basis of the new industry.
A spokesman for Diagnostic Centers for Men, founded in 1990, says the company now has 30 offices across the country, more than 30,000 men have been seen, and that 51 percent have been treated with injectables. Men's Health Centers - founded in 1993 and affiliated with the impotence center at Boston University Medical School - has four offices in Florida, and sees between 60 and 100 men each month. The majority are in their 50s and 60s.
In January 1996, two alumni of UMDNJ-New Jersey Medical School - Bernard Lehrhoff and Malcolm Schwartz - became principals in a new company, Impotence Centers of America (ICA). It has four offices in northern New Jersey, one in New York City, and plans to go national in a couple of years.
Lehrhoff, the founder and medical director, explains how it got started: "Impotence was always a large part of our practice, but when you know how many millions of men there are out there, you know you're only scratching the surface. We assumed it was embarrassment that kept them from getting help, but I didn't like the idea of physicians advertising."
He came up with the concept of a company - it doesn't bother him if a company advertises - with a different slant. To make it easier for men to seek help, ICA has only one patient in its building at a time.
"It's an expensive approach," Lehrhoff notes. "In my urology practice I can see 40 patients a day if I work late. At ICA, I can see only eight. We manage, however, because much of the preliminary work is done during the first visit by our technicians." They begin by taking a four-page history that helps point to what could be wrong.
It takes a coordinated interplay of nerves, blood vessels and tissue to produce an erection. Two chambers, the corpora cavernosa, run the length of the penis; they consist of spongy tissue laden with blood vessels. The walls of these vessels are smooth muscle, and when constricted they leave little room for blood. Erotic stimulation causes nerve endings in the penis to release neurotransmitters, including nitric oxide which relaxes the muscle and allows the corpora cavernosa to fill with blood. The engorgement temporarily prevents veins that normally drain blood from doing so, and the result is an erection.
Circulatory problems caused by smoking, diabetes, high blood pressure, etc., can thus affect sexual function, as can the kind of neuropathy that occurs with diabetes. And to make matters worse, many drugs used to treat these and other disorders can also have an adverse affect.
Based on the results of the questionnaire, ICA technicians do diagnostic tests for blood and hormone levels, loss of penile sensation, and studies that measure whether there is an adequate blood supply to the penis.
"In taking a history," Lehrhoff explains, "if a man tells you he wakes up at night or early morning with good erections, you have to think there's a psychological component to his problem, and it may not be necessary to do the whole rigmarole of testing. But if he says he wakes up with an erection that's weak, then you might suspect a venous leak and you'd move on. The technicians are distinguishing psychological from organic causes and separating premature ejaculation from erection problems."
At the second session, patients see one of the five staff urologists. If necessary, duplex penile ultrasonography is done. It's an expensive test - between $400 and $500 - that first requires an injection to induce an erection. Then the flow of blood into the penis is measured, as well as how fast it drains. It is during this visit that the causes of dysfunction and therapies are discussed.
Lehrhoff and ICA were written up in the June 1996 issue of Men's Health, which led to appearances on CNN's "Health Watch" and calls to ICA. "But only weeks later," he notes. "It takes a long time for a man to take that step. We always ask how a patient has heard about us. Recently one said he saw me on News One. That was a year ago."
The article focused on Irwin Goldstein, MD, of Boston University Medical School, who began an impotence treatment center there in the early '80s. He was a principal investigator in the landmark Massachusetts Male Aging Study that is the main source for statistics on erectile dysfunction in the U.S.
The study found that 53 percent of men over age 40 sometimes had erectile problems, and experts say that only about 1.4 percent of men are treated. "Don't call it impotence," they plead, although many belong to the International Society of Impotence Research. Rosen says the term is pejorative. It's not clear that calling it erectile dysfunction will make men feel okay about it, but the recognition of physical causes has undoubtedly made it a little easier for them to admit and deal with it.
Yet Rosen cautions, "It's a terrible mistake to dichotomize erectile problems into medical and psychological. A lot of physicians have encouraged that."
Lehrhoff agrees: "A few failures can certainly increase performance anxiety, even if the major problem is diabetes."
Urologist Eli Lizza, an alumnus of New Jersey Medical School and a clinical associate professor there, has been treating erectile dysfunction for 11 years. It now accounts for about 60 percent of his New York City practice.
Lizza, who directs the school's division of male reproductive medicine, explains that sexual dysfunction is more likely to happen to men as they age and to those with predisposing factors like smoking, high blood pressure or diabetes.
"The average patient is somewhere between late 40s and 70s, and he's been having problems for a couple of years," Lizza observes. "He's often in a new relationship. Maybe he was married for 20 years or more, and sex had become a non-issue. Now, he's divorced or his wife has died - he's in a new arena and sex is important, either for his own satisfaction or for his self-esteem."
Men who have sexual dysfunction because of radical prostate surgery for cancer can be helped Lizza says, "but first you have to determine the nature of the problem. They can easily have nerve or arterial damage. And then there is the psychological aspect." He explains that these men may be depressed about the disease itself, and they may also have some performance anxiety because they know the surgery can affect erectile function.
All the experts note that since dysfunction increases as men age - and many men having prostate surgery are in their 60s and 70s - they may have been having difficulties before the surgery.
Bicycle injuries are another physical cause for dysfunction, Lizza says: "There is chronic compression between the bicycle seat and the pubic bone. The compression becomes acute when you hit a bump. Nerves and arteries can be injured. One thing to be on the alert for is numbness in the genitals." He suggests not riding with a narrow racing seat unless it is padded, and recommends a gel pad about an inch thick, pads in the racing pants, or using a flat wide seat.
For those who have been injured, the injectables - papaverine, phentolamine and prostaglandin E - are likely to help. These vasodilators had been used to treat cardiovascular problems.
They were introduced as therapies for erectile dysfunction in the U.S. at a memorable meeting of the American Urological Association in 1983. According to an article in the November 16, 1996 issue of the Village Voice, British researcher Giles Brindley had injected himself before addressing the conference. He walked to the podium - clad only in his underwear - dropped his drawers, and presented his empirical evidence.
The most popular injectable is Pharmacia Upjohn's Caverject, which was approved by the Food and Drug Administration for erectile dysfunction in 1995. It contains prostaglandin E. Some physicians, however, are using a mix of three vasodilators. Lehrhoff says these medications work about 90 percent of the time, the needle is small, and the procedure is not particularly painful. He adds that pain is usually due to the medication, and the patient can simply switch to another drug.
The FDA has recently approved an autoinjector device that should make it easier for men to use Caverject, but Lizza has some qualms about it: "You can get fibrosis from the injectables - from injecting the drug into the wall of the corpus cavernosum, rather than the space. You get to know by the feel of it whether you are injecting the right place. With the autoinjector, you won't have any sense of that. I'll recommend it only for men who have needle phobias."
So, who wouldn't rather take a pill? Besides being easier, Sildenafil is likely to cause few side effects because it is selective. Two enzymes crucial for an erection are cyclic GMP and PDE5. Nitric oxide depends on cGMP to relax the corpora cavernosa. The second enzyme, PDE5, breaks down cGMP, causing the erection to subside. Sildenafil targets PDE5, preventing the breakdown and prolonging the erection.
"Since PDE5 is more prevalent in the penis than elsewhere in the body," Lizza explains, "the drug is less likely to cause side effects. The reason you get them with so many drugs is that they affect the whole system."
Sildenafil's erectile enhancing ability was actually discovered as a side effect. The drug was originally used to treat coronary angina. When patients reported that it caused erections - voila!
The drug is being tested mainly in healthy men whose problem is considered psychogenic. It is taken an hour before having intercourse, and it has helped 60 to 80 percent, twice as many as other therapies, says Lizza.
"But even if all the initial data for men with organic causes is favorable," he adds, "it doesn't mean we'll get the same results when we have large-scale studies. Take Proscar, for example, which is used to shrink an enlarged prostate gland. It was great in clinical trials, but in the general population, it was not as successful."
All of these doctors attended the International Society for Impotence Research meeting last November. And all say the big news was "the pill." And the reaction to the news? Discreet cheering. After all, this is a rather conservative group, in a different kind of arena.
Penile implants first used in the 1950s are much improved, but they are still considered a last resort by patients and physicians. There are about six types available. A malleable version consists of semi-rigid rods that are implanted under local anesthetic. The concept works on the same principle as a goose-neck lamp.
Another, a self-contained inflatable that can often be implanted under local anesthetic, consists of cylinders that are filled with a sterile fluid. It requires some dexterity to inflate and deflate and is not as rigid as the other implants.
Surgery for the fully inflatable implant usually requires hospitalization and general anesthesia. It involves implanting the cylinders in the penis, a fluid reservoir under the stomach muscles, and a pump in the scrotum. Squeezing the pump several times forces saline solution from the reservoir into the cylinders. The penis will remain erect until the solution is forced back into the reservoir. Dr. Lehrhoff calls this the best of the implants - it most closely resembles a normal erection - and says it requires one incision about three inches long. Dr. Lizza says the cost of implants is between $3,000 and $5,000 for the devices, plus additional fees for surgery, hospitalization and anesthesia.
A vacuum pump device, patented in the '40s, works by placing the penis in a tube and pumping air out to create a vacuum. It increases blood flow, resulting in an erection. A ring is then slipped on the penis to prevent the blood from draining. There are no serious side effects, but Dr. Rosen notes that "it is awkward and mechanical, and produces erections that are not as firm as most men would like." The device costs about $400.
Caverject and the other prostaglandins require an injection into the side of the penis about 10 minutes before having intercourse. The dosage must be worked out in the doctor's office and may require a couple of visits. The medicine, sold in a six-pack for about $25 per dose, is usually covered under insurance and prescription plans.
The Muse System, manufactured by Vivus, employs an eye dropper-type device to insert a pellet of prostaglandin into the urethra. Lehrhoff says it will be available in February and will cost $25 to $30 for each dose.
Beginning in the 1980s, testosterone was traditionally given to men with erectile problems, and it helped those with low hormone levels. But that seems to be a problem for less that 10 percent of men.
Traditional remedies like yohimbine, which is made from the bark of a tree, have long been used in Africa and Central America. Yohimbine has been used in the U.S. since the 1920s, and is sold in health food stores. Rosen, who is directing a study on it, says it was found to be unreliable, even as to how much gets into the blood stream. He adds that the drug works systemically - not specifically as a sexual stimulant - and that some men report becoming nervous and even anxious. When it is effective, only 50 percent of men report improved erections.
Lehrhoff notes that European specialists at the International Society for Impotence Research in November told their American colleagues they weren't using yohimbine correctly. The Europeans give eight doses a day, while in the U.S., the FDA has approved only three a day.
Some physicians are trying combinations of drugs. Lehrhoff says he uses a mixture of yohimbine and Trazadone, a tranquilizing sedative that has a side effect of prolonged erections.
Topical ointments containing such ingredients as prostaglandin E, minoxidil, or herbs are also used. But none of the experts interviewed thought they compared well to other therapies.
