Urology Times Innovation Celebration: Expert Insights

Dr. Burnett on Viagra: “This transformed the field in a significant way”

Urology Times® is celebrating its 50th anniversary in 2022. To mark the occasion, we are highlighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, Arthur L. Burnett, MD, MBA, FACS, discusses how sildenafil citrate (Viagra) is and has been an integral part of erectile dysfunction (ED) management for decades. Because of this drug’s efficaciousness, Burnett emphasizes that patients with this condition can be treated without the burden of invasive side effects. Burnett is the Patrick C. Walsh Distinguished professor of urology and oncology at the Johns Hopkins University School of Medicine and the James Buchanan Brady Urological Institute in Baltimore, Maryland.

Please provide an overview of the development of Viagra for treatment of erectile dysfunction.

Viagra is a term for a medication [used] to treat erectile dysfunction that we all know. Some would say unless you've been on another planet the past 20 years, there's no way that you could not know what Viagra is. It's as well-known as Coca-Cola. It’s a well-known treatment for erectile dysfunction. It’s gained prominence in commercials and advertisements. And given the prominent condition of erectile dysfunction as a form of sexual dysfunction among men, it has certainly come to the forefront. The drug itself has gone through several iterations of names. It originated as this drug called UK-92,480 and was studied as a medication to treat angina. In the early studies that were being done with this medication, about 30 years ago now, [there was] an interesting observation among the clinical trial investigators. Also, [at] about that time was where the science of erection started to come about—the science of erection having to do with nitric oxide and the signaling pathway that we all hear out there. This is a scientific pathway that we understand now is a true mechanism of penile erection. Fortunately, I had a major role in the science of all of that. So, when that science started to emerge, the observations in the trial for the heart condition [were] amazingly that patients were saying, "It's not helping my heart, but my erections are enhanced." Once it was put together that it followed [the] recently described scientific pathway for erection, that's when the drug came about. It became known as sildenafil, which is a generic term, and then the company, Pfizer, who was behind all this, brought it forward as Viagra.

What are some of the other innovative treatments for erectile dysfunction that have become popular in recent years?

In recent years, we have continued to bring forward treatments with consideration of lesser invasiveness [and] greater ease of administration. So, obviously, oral therapies remain highly popular and there are versions now of agents like Viagra called PDE-5 inhibitors. Now, there are 4 that are available on the market. The course of management with oral therapy [is] effective now, which is really lightyears ahead of where things were decades ago with various herbs and supplements that may also have been taken orally but were not very effective. So [it's important to] know that that's been a major theme that's continued. There has been some interest to move forward with other new options that may meet a new goal of not just treating erectile dysfunction, but possibly curing erectile dysfunction. We use that word “cure,” which, to some extent, means that we're trying to correct the underlying pathologic conditions in the penis. Erections require the best health of the penile tissue, so these ideas have emerged in recent years to do restorative therapies or regenerative therapies. That's the message that I'm saying. I think that these therapeutic prospects are still in development, so I don't know whether we can claim that they're fully established therapies, which are such novel [mechanisms] as shock wave therapy or platelet-rich plasma. I have to be entirely forthright in saying I think that these are therapies that remain investigational still. They may have potential, they may fit with ideas of healing the penis, which I think is the direction we want to go in, but they remain to be fully investigated, and have not yet been established within guidelines to be authentic therapies just yet.

What do you foresee as innovations on the horizon for ED treatment in the near future?

In the next year, we don't have a whole lot more than what I just mentioned. I think there will continue to be refinement of existing therapies, at least in the short term. We have a range of options that, as I mentioned, go from oral therapies to more intermediate or semi-intrusive or invasive options, like vacuum erection devices [or] penile injections. We also have somewhat more intrusive surgical interventions that might be truly irreversible, such as penile prosthetics and that sort of thing. I think there will continue to be innovations along the way, particularly with regard to prosthetics. I see that in the near future, with some exciting new developments of possible automated devices, easier-to-use devices, things of that sort. So, be on the lookout for that. [It] may be fairly imminent; give it a couple of years. We may continue to refine our pharmacologic therapies. I think more long term will be some of these regenerative therapies. To see them truly studied and shown to be effective, they may still be several years down the line.

As further treatments are developed and refined, what is Viagra’s legacy in the treatment/management of ED?

I do think there is a legacy associated with Viagra. I think it inaugurated an era of treatments that we've never seen and never had before. Who would [have] ever thought we would have an effective oral therapy, [one] that in a way you take in your body orally, but somehow gets to the penis and has an effect there? That almost blows the mind to even consider how that would even happen. In fact, it's based on the science of nitric oxide. Again, nitric oxide is the feature story here. It has a mechanism that is such that it cleverly represents a pathway in the penile tissue that, with an oral therapy, can exploit that. And so, it's inaugurated oral therapy has changed how we go about the practice of sexual dysfunction management in men. It's been a true revolution, an intervention, if you will, for the field of sexual medicine. Its legacy will be that this has transformed the field in a significant way.

How did Viagra revolutionize the way in which erectile dysfunction is treated and managed?

Viagra has revolutionized the field of sexual medicine and impacted how we go about therapies. I think it's opened our eyes to the possibilities. There [are] so many different dimensions of its impact. I think that it's helped us remove the taboo surrounding sexual dysfunctions. It's enabled us to recognize that it can be appropriately treated without saying it needs to be overly medicalized. It used to be that erectile dysfunction was a psychological problem or emotional problem, or a matter of interpersonal relationships, and therefore always in the domain of the psychiatrist or psychologist. We've evolved in the past 2 decades or more to understand that it is a physical problem, by and large, and related to health conditions of patients, and there's a real disease state surrounding it. So, it's helped us really get down to understanding that it can be treated, that erectile dysfunction can be addressed with physiologic treatments that can be effective. It's helped us open up our eyes so that this is no longer a taboo subject, and that we can talk about it. It's helped us think about female sexual dysfunction. It's helped us recognize that the whole area of sexual medicine and sexual health is an appropriate subject matter, and treatments that can address all aspects of sexual dysfunctions in men and women are fair game. We want to make sure that people have improved qualities of life, and therapies that can address all of this. [It] is entirely open season for how we can move forward to help all of our patients. [Viagra has] had an impact in very dramatic ways.