For the millions of men affected by erectile dysfunction, there are a variety of proven successful options. Many first-line oral treatments can even preserve spontaneity while alleviating the side effects of past treatments.
In the realm of erectile dysfunction (ED), the news is surprisingly positive for a disease that impairs quality of life for some 30 million U.S. men. With drugs being approved for use in multiple ways and at various times, treatment options for men with ED have never been more widely available. Phosphodiesterase type 5 inhibitors (PDE5is) revolutionized ED treatment in the 1990s, but now scientists are discovering just how flexible these vasodilators can be. Men with ED who desire treatment not only have more choices available to them, but they also can be more confident than ever before successful treatment is within reach.
The short-acting PDE5is sildenafil citrate (Viagra), vardenafil (Levitra), and avanafil (Stendra) and the longer-acting tadalafil (Cialis) were formerly used only on an “on demand” basis. The short-acting compounds were thought to be best taken on an empty stomach, or in the presence of a low-fat meal, 30–60 minutes before engaging in some kind of sexual interaction. It turns out, some of them do not require such strict administration regimens. In a recent clinical trial, researchers led by Wayne J.G. Hellstrom, MD, FACS, professor, chief, Section of Andrology, Department of Urology of Tulane University School of Medicine in New Orleans, demonstrated that avanafil provides a rapid onset of action in many men as quickly as approximately 15 minutes. “Many ED patients are looking for a safe and effective treatment option that also works fast,” Hellstrom says. The placebo-controlled trial of 440 men also showed that avanafil can be taken with food (or without) and with alcohol.
“Tadalafil is a little bit different in that it is much longer acting — patients can get 24 to 36 hours out of one pill,” says Evan R. Goldfischer, MD, MBA, coCEO and director of research, Urology Division of the Premier Medical Group in Poughkeepsie, N.Y., who has studied tadalafil’s flexibility. “Tadalafil does not interact with food, and many patients like the spontaneity that it allows because you take it one to two hours before you want to have sex, but you have a good 24 to 36 hours before the tablet is no longer effective,” he says.
Tadalafil also provides administration flexibility. In “Impact of Low Testosterone on Response to Treatment with Tadalafil 5 mg Once Daily for Erectile Dysfunction,” published in Urology, Goldfischer and team reported that very low doses of 2.5 or 5 mg daily are also very effective. “Some patients find that the side effects are less, and it allows them to have a lot more spontaneity. They are taking it every day, so essentially they are always ready to go,” he says.
An added benefit of tadalafil is its indication for benign prostatic hyperplasia (BPH). Many men in their 50s and 60s not only suffer from erectile dysfunction but begin to experience prostate enlargement, which makes emptying their bladders more difficult and impedes urine flow. “So a lot of men will take tadalafil on a daily basis not just for sex but also for the BPH as well,” says Goldfischer.
Side effects will differ depending on which receptor each PDEi cross-reacts with. For example, sildenafil citrate can cause cyanopsia — or blue vision — because it reacts with the type 6 receptor in the retina, whereas tadalafil can cause back and muscle aches when it crossreacts with the type 11 receptors located in the back. However, as researchers point out, some of these side effects can be ameliorated with smaller daily doses, which still provide enough vasodilation to achieve an erection satisfactory for penetration.
But adequate circulation is only one part of the equation — although it is critical not just for achieving erection but also as an indicator of overall health. Because the artery to the penis is very small, it will probably be the first to demonstrate signs of atherosclerosis. Goldfischer says, “Even a patient for whom sex is not all that important should still tell his doctor about any ED and be evaluated, because, at the end of the day, it might not be the penis that needs treatment, it might be the heart or the brain to prevent heart attack or stroke.”
Besides an intact vascular system, intact endocrine and parasympathetic nervous systems are also necessary. In men with diabetes, both systems can be compromised, which might affect their ED treatment. A man with very low levels of testosterone, such as from significant diabetes or from prostate cancer treatment, may not have much interest in sex to begin with. Although the typical treatment until very recently was to replace the testosterone, Goldfischer’s study demonstrated that even low levels are sufficient for erection in conjunction with tadalafil therapy. Testosterone replacement is controversial because many feel that the benefits — increased energy, mental well-being, and sex drive — do not justify the adverse effects of hepatic and renal toxicity, prostate enlargement, and possibly atherosclerosis. “Our paper is meant to guide physicians,” says Gold- fischer. “If a man comes to you with ED and a serum testosterone level of
Thus, the PDE5 inhibitor offers many men effective therapy, especially with recent advances in the variety of administration options. But they are not able to treat every man with ED. “We really do need to treat every patient as an individual,” Goldfischer says. Nowhere is that more true than in men with diabetes, who are especially prone to nervous system and vascular injury, which places them at significantly higher risk for ED.
In “Men With Diabetes May Require More Aggressive Treatment for Erectile Dysfunction,” published in the International Journal of Impotence, researchers led by Thomas J. Walsh, MD, MS, associate professor of urology at the University of Washington and director of the UW Men’s Health Center in Seattle, reviewed claims from the United Heathcare database and found that among men with ED, those who had diabetes seem to be more likely to seek advanced treatment options. “That suggests that physicians and providers should be more attentive to the needs of men with diabetes and ED,” Walsh says. The takeaway for clinicians is that patients require good counseling. “We should let them know that it is more common for first-line oral treatments not to be successful in men with diabetes, and it is more likely that they may need more advanced levels of care, simply because their ED is more severe than an average man’s.”
ED treatment should be stepwise, but men with diabetes may need to move through the steps more quickly. Walsh advises primary care doctors and endocrinologists to contemplate referring diabetic patients to a men’s health specialist or a urologist earlier rather than later to discuss all options. “All of these men are capable of achieving their goal with successful treatment,” he says. “It just may mean that achieving their goal may require more intervention.”
cornerstone of successfully treating this quality-oflife disease. In the realm of pharmaceutical treatment, Goldfischer says, “Explain the risk/benefit profiles of a medication and its administration options to patients and develop the right pharmaceutical regimen that is right for them.” They should also be informed that when medication is not enough, the door to successful treatment does not have to close. “Treatment is elective and goal-based,” Walsh says. A key part of referral is making sure a patient understands all the options associated with his particular goals. And with that in place, says Walsh, “success is imminent.”
— Horvath is a freelance writer based in Baltimore, Md.
She wrote about delayed puberty in the October issue.