Every so often, a medication comes along that has the power to change the way a disorder is managed--and to dramatically increase the number of people treated.
By most accounts, that is the scenario expected when sildenafil--for the treatment of impotence--is approved by the Food and Drug Administration and reaches the marketplace, probably within months.
Sildenafil, sold by Pfizer Inc. under the brand name Viagra, will become the first oral medication for impotence--or erectile dysfunction, the preferred term among urologists. Studies show Viagra helps about 60% to 70% of men with physical impotence and more than 80% of those with psychological impotence.
An estimated 18 million American men suffer from erectile dysfunction, most of whom could be successfully treated. Yet only about 5% seek help. Embarrassment may be only part of the reason for their reluctance. Until Viagra, the treatment options for impotence ranged from implants to vacuum pumps to injections into the penis to suppositories into the urethra--options that most men find none too appealing.
The ability to simply swallow a pill and, within 20 to 40 minutes, have a normal erection after sexual stimulation may send impotent men to their doctors in droves. And it may even lower the threshold for what is considered impotence.
"Viagra is without question an amazing therapy that will have a huge potential benefit to men," says Dr. Harin Padma-Nathan, director of the Male Clinic in Santa Monica and well-known researcher in the field. "Oral medications have dramatic appeal. They are pills that you can take when you want to take them. But the most critical aspect for a drug for erectile dysfunction is that it's safe."
Several other companies are nearing completion of research on oral medications for erectile dysfunction as well. And Padma-Nathan, who is also a clinical associate professor of urology at USC, is about to launch a study to see whether the medications can even prevent impotence.
But Padma-Nathan cautions that Viagra and the other pills that will follow it are not fuel for a "sexual revolution."
"It is not going to change men's behavior. It is not an aphrodisiac," he says. "It will not alter libido. The medications improve erections in men who have erectile dysfunction. They don't change erections in men who are normal. [The medications] have no potential for abuse."
Yet, studies of Viagra and the other oral medications show they do have the ability to transform lives.
Even though he underwent a radical prostatectomy for cancer with a good attitude "since I'd never had a problem in that area," Tolman Geffs was dismayed to find the 1995 surgery did cause erectile dysfunction. He and wife Jill, who are 64 and 58, respectively, had married in 1990 and had just seen the last of their children and stepchildren grow up and leave their Orange County home.
"We were newlyweds," Tolman says. "We were empty-nesters with freedom. But, as the male, even though I knew Jill loved me, I had this horrible fear of, 'Am I going to lose my mate?' "
"We had just discovered each other," adds Jill. "We have this wonderful love, and I wondered, 'Am I going to lose this man to cancer?' "
Tolman turned to Padma-Nathan for treatment at the end of 1995 and decided to try Caverject, the first injectable medication for erectile dysfunction. The drug worked but caused side effects.
"It was far, far from a desirable solution," Tolman says. "The hormone left a severe aching sensation--talk about aching for love! Then, pretty quickly, I ran into a problem with scar tissue [from the injection]."
While injections are a significant advance in treatment, they can also cause prolonged erections.
At that point, Padma-Nathan had begun using Viagra in clinical trials and offered Tolman a chance to join the study. It's been bliss ever since.
"You take this drug, and you have the spontaneity of a normal, married life," Tolman says. "We think the drug is wonderful."
According to Padma-Nathan, the research participants were so enthused about Viagra that, after the study was completed, they petitioned Pfizer to request continued use of the drug under a "compassionate extension" protocol.
"It's astounding how effective it is with men in organic dysfunction," says Padma-Nathan, who will present new data on Viagra at the American Urological Assn. meeting in San Diego in May. These organic conditions include men with post-radical prostatectomy impotence, diabetes, severe vascular disease and spinal cord injuries.
Daniel, 52, was diagnosed with diabetes about seven years ago. When he began to experience erectile dysfunction a few years later, he didn't make the connection that the diabetes was probably causing the problem. But his wife, a nurse, did.
"My wife and I are good friends and we could talk about it," Daniel says. "She said, 'I think I know what the problem is.' "
He sought treatment and used the injected medications until he enrolled in the Viagra study Padma-Nathan was directing.
"The injection worked, but you have to be careful with the dosage. And, after you take it, you're not going anywhere for a while," he says. "The oral medication is a piece of cake. It's as natural as if you don't have any disease that causes a problem."
Bob, 63, sought treatment for erectile dysfunction within months of his radical prostatectomy and now encourages fellow cancer patients not to delay in seeking help after healing from surgery.
"The sooner you get back to some kind of normalcy, the better," he says. "I didn't do this for sex. I did this to get back to being a normal, male person. As it turned out, I'm really happy I did. I met a woman about six months ago, and we're planning on being together and getting married."
Bob and Daniel, both of Los Angeles, are both delighted not to have any side effects from Viagra. According to Padma-Nathan, about 10% of men using Viagra experience headaches, stomachaches or muscle aches. Only 2% of the men in clinical trials dropped out because of side effects.
Besides those rare individuals who can't tolerate side effects, Viagra cannot be used by men who are taking nitrates, such as nitroglycerin for coronary artery disease, says Dr. Drogo K. Montague, director of the Center for Sexual Function at the Cleveland Clinic Foundation.
Although Pfizer has not announced a price for Viagra yet, it is expected to be affordable and covered by insurance. Not surprisingly, Pfizer's stock has soared in recent months as word of Viagra's potential has spread.
"I think what we'll see is that everyone on the other therapies, such as Caverject, will want to try Viagra," says Steven Tighe, senior pharmaceutical analyst for Merrill Lynch in New York City. "But Viagra won't be effective for everybody. There will be a subset who won't respond and who will need to stay on the other therapies."
Until the early 1980s, doctors did not have a good understanding of the physiology behind erections and, thus, were hampered in their treatment options.
"From the mid-1970s to the mid-1980s, penile implants were all we had to offer," Padma-Nathan says. "Injection therapy was the springboard that changed everything. As a result of the effectiveness of injection therapy in relaxing the smooth muscle, we at least knew that drug therapy was possible."
Viagra was first tested as a heart medication, but researchers quickly realized that the medication acted on erectile tissue.
In healthy men, sexual stimulation triggers a surge of the neurotransmitter nitric oxide. It, in turn, releases a chemical called cyclic GMP. Cyclic GMP causes the smooth-muscle cells of erectile tissue to swell.
Viagra eases the process by blocking an enzyme found mainly in the penis that breaks down cyclic GMP.
"The last three to four years have been so amazing," Padma-Nathan says of the research efforts. "I didn't think there would be a pill in my lifetime--let alone three."
Another drug, apomorphine, in clinical trials is different from Viagra in that it acts in the part of the brain that is associated with initiating erections. In the future, a combination of medications that act centrally and peripherally may prove to be the best remedy, Padma-Nathan says.
"What you see is the tip of the iceberg," he says.
There is some concern that the question of "what is impotence?" may change with the advent of oral medications. Will occasional dysfunction be reason enough to obtain a prescription? These questions are important because primary-care doctors may become the major dispensers of the medications.
"Hopefully, the drug will be used wisely," Montague says. "Some men complain about erectile dysfunction, but the problem is really a failing relationship. We have learned with other treatments that it's a waste of time to treat erectile dysfunction until the relationship problem is addressed."
But, he adds, the drug may be perfect for men who have occasional failures and become so anxious about it that they make the problem worse.
"Every man reaches a point in his life when they have occasional failure. Hopefully, they recover from it. But a pattern of anxiety may emerge, and failure may become well-established. This is where the drug may be particularly helpful," Montague says.
Some trial and error will be necessary after the medication reaches the marketplace to determine just how it can help and who will benefit, doctors say.
"The guidelines for prescribing have to be better defined," says Padma-Nathan, who adds that a process is underway to develop guidelines in the primary-care setting. "You need certain minimum requirements, such as having consistent dysfunction for three to six months. These guidelines, hopefully, will prevent better use of the medication."
Typically, only men with severe problems have sought treatment. But that may finally change.
"There are so many men who don't know that this problem can be easily fixed, and they have relationship problems because of it," says Daniel. "Why should your life be wrecked when it's so simple to fix? People think erectile dysfunction carries a stigma. But if you have a medical problem, fix it."