What exactly does Erectile Dysfunction (ED) mean?
Erectile dysfunction (ED), that is, difficulty in getting or maintaining an erection that interferes with sexual intimacy, until 15 years ago, was in the closet, labeled “impotence.” Then came along a drug called sildenafil, which was tested by Pfizer to treat heart disease symptoms, like angina. It flunked the tests, but when men started chortling about all the erections they were experiencing while enrolled in the study, sildenafil was taken off the shelf and earned FDA approval for erectile dysfunction.
Why treat ED?
Anyone who asks this has never had it. 100 million men worldwide do, however. Intercourse is so important that many religious and civil definitions of marriage use it as the criterion that consummation of marriage. This is somewhat an intrusion of privacy, because there are many asexual unions that work fine. But the majority of unions that suffer ED do not work fine. They struggle.
It takes two to tango, but when one cannot dance, the song’s over. Erections are just as important to women as to the men with whom they’re intimate. ED, compromising sexual intimacy to the point where penetration is difficult—if not impossible—is frustrating to the couple. It is a social emergency.
Enter sildenafil…and the other phosphodiesterase-5 (PDE-5) inhibitors.
After being blindsided by pure luck, Pfizer’s sildenafil, fresh from FDA approval for ED, hit the market as “Viagra” in April, 1998, and sold almost half a billion dollars’ worth in its first three months. For the first time, the significance of ED was able to be appreciated. The closets could be counted. Savvy marketing, including a spokesperson from politics, pushed the “little blue pill” to new heights, rising faster than an erection itself.
Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor, inhibiting the metabolism of nitric oxide which is important in blood flow and erections. Less nitric oxide means less blood flow…means less erection; so inhibiting its disappearance is a good idea for ED. Although most really don’t care how it works, still it is important to know this because of the conditions common to many of those with ED—cardiac disease. The nitrate medications that control blood pressure help the circulation in the coronary arteries by relaxing these blood vessels, the same way that sildenafil—the failed antihypertensive—works. PDE-5 undoes all the erection-causing effects of nitric oxide, so opposing it will enhance nitric oxide’s effect, not only in the penis, but everywhere else. Add another nitrate medication to the mix and there may be a 9-1-1 call in it for somebody who suddenly collapses in hypotensive shock.
In spite of that, the PDE-5 inhibitors have been very popular, first with sildenafil (Viagra), followed by vardenafil (Levitra) and tadalafil (Cialis). The very nature of the nitrate properties have always made awareness of the dangers a package deal when they are offered by a doctor.
How is ED treated?
Libido is important, too, and should not be ignored. No pill can fix it, because it may be caused by testosterone, psychological, or marital issues, which must be addressed at the same time as ED. Libido aside, the erection problem itself is addressed via a management flow sheet developed by the American Urological Association:
- First line therapy: medicines that increase effects of nitric oxide to relax the channels in the penis for increased blood flow.
- Avanafil (Stendra), the new second-generation PDE-5 inhibitor, boasts an even more rapid onset of action.
- Second line therapy: directly interacting with the penis (urethral suppository, injectable alprostadil, vacuum pump).
Third line therapy: surgery (penile implant, surgical correction of the scarring in Peyronie’s disease, surgical repair of the vascular supply).
As can be surmised, these go through the ever-increasingly aggressive therapies. Most men only require the first line therapy.
Sildenafil (Viagra) helps even those who do not complain of ED, because it has been shown to benefit men suffering from “mild” (incomplete) ED, diabetes, and men who have undergone removal of the prostate, especially when sparing one or both sides of the nerves around the prostate. Sildenafil needs an empty stomach for its best absorption, about an hour before sex. It should be begun at the 50 mg. dose, and this can be increased if the erection is not satisfactorily, or decreased if there are side effects. It lasts for about four hours.
Vardenafil (Levitra) is more like sildenafil than tadalafil (Cialis) is (see below). It is similar in molecular structure, onset, side effects, and the four-hour duration, and like sildenafil, it has proved helpful in ED due to diabetes or prostatectomy. It now has been made available as an orally dissolving tablet for more rapid onset, which eliminates the coordination needed to take Viagra before meals. This adds the benefit of spontaneity.
Tadalafil (Cialis) has a different type of molecule, but has the same success rate that Viagra and Levitra enjoy. The difference is that it has a longer lasting effect, sometimes as long as a day or more. It also is used when ED is caused by BPH (benign prostatic hypertrophy—or enlargement), which Viagra and Levitra don’t share in their indications.
Another benefit of tadalafil (Cialis) is that it can be taken daily at a lower dose, for a maintenance program of continuous “potency.” This has yielded very high success rates.
Which one is best?
Because they all work as PDE-5 inhibitors, they all work well. The American College of Physicians recommends, therefore, that the choice be based on a patient’s preferences regarding costs, duration, and side effects.
What are the side effects?
Because they can lower blood pressure, they can interact with other medicines (nitrates) used for hypertension. Careless co-administering nitrates while the PDE-5 ED treatment is still onboard can result in sudden death from cardiac death. Because of this, at least 48 hours should pass after taking one of these drugs, before administering a nitrate.
Other, less scary, side effects include:
- Nasal congestion
- Visual changes (“blue vision”) has been reported with Viagra alone, since there is a PDE-6 in the retina with which it can cross-react. It has been reported that the optic nerve can lose its blood supply, which is probably, just after carelessly causing cardiac death from adding nitrates, the next most serious side effect. Thankfully, this is rare.
- Hearing loss, again rarely reported, is usually temporary, but in 1/3 of patients it can last indefinitely on one side within 24 hours of taking the drug.
Because these drugs are seen as sexual enhancers, there is much myth and considerable abuse by those who do not need them. This unsupervised use will no doubt add to the list of side effects and contraindications in the future. Also, playing on the notoriety of sexual adventures, dietary supplements and counterfeit medications are continually popping up. The FDA condemns these as bogus.
Who shouldn’t take them?
Again, those taking nitrates, as is mentioned numerous times above.
Some patients with enlarged benign prostate glands (BPH) may experience a drop in blood pressure when they mix the alpha-adrenergic antagonists (“alpha blockers) used in BPH with the PDE-5 inhibitors used for ED. It can be done, but requires the direction of the patient’s physician.
When the little drug that couldn’t caused unexpected erections in men enrolled in its studies, it became the little drug that could. Further tweaking, as in the second generation drugs being introduced, will no doubt hone the precision of the effects such that the side effects and contraindications may disappear one day. In the meantime, prudent use of a physician’s precautionary direction will keep men safe so that they can treat their ED; and if you consider their partners, they won’t be the only ones to benefit.