The Road to Sildenafil - A history of artifical erections

The inability to achieve erection has been a source of consternation for men for, well, a really long time. But the recent history of treatments for impotence, wait, I mean Erectile Dysfunction, oh no, now they're calling it Male Sexual Dysfunction, represents a medical revolution. In the last 100 or so years, we've gone from nonspecific and largely ineffective treatments, to progressively more successful treatment, finally resulting in a highly specific and effective pharmaceutical solution to the problem. The goal of this post is to share a history of this unique field of medical endeavor, the medical and biological insights we've gained, and the rather interesting characters involved along the way.

Erectile dysfunction is reported in about one out of five of all men and increases with age. It is therefore a serious problem for millions of American men (and their spouses a fair amount of the time), and hundreds of millions worldwide.

Our story starts with one of the earliest "medical" treatments for male impotence. Starting in the late 1800s, sheep testis extract was injected as a source of testosterone (although they didn't know it at the time). This was the standard of care until testosterone was purified in the 1940s. However, testosterone as a treatment for impotence was pretty poor. The inability to obtain an erection has little to do with levels of androgens, and in studies at the time testosterone fared no better than placebo.

Thus, this was the treatment that failed for Geddings Osbon in 1960, leading to the next great leap forward in treatment of male erectile dysfunction. Osbon, a successful owner of a tire-retreading business, did what doctors dread their patient will do. He went home and looked around his shop and home and tried to come up with a solution to his medical problem. Usually, this results in disaster, and many doctors have hilarious stories of the attempts of such patients to cure less mechanical disorders with household materials. However, in this case, Osbon invented a device which he called the "YED" or "youth equivalence device" that is still today one of the most effective solutions to erectile disfunction. It's also known as the penis-pump.

I'm afraid the rest must continue below the fold. I think it's safe for work, but you never know...the description of probably the most infamous urology lecture of all time might be a bit much.

The device, which now goes under the moniker Erecaid, looks something like this.

It works, because of the nature of how the penis becomes erect. The penis is like a sponge that is being compressed. The sponge in this case is the corpus cavernosum and spongiosum, and the compression is coming from the smooth muscle of the arteries feeding the sponge which prevent blood from flowing in.

With relaxation of the smooth muscle surrounding these arteries, blood can then flow into the cavernosum and spongiosum, and the spongy organs then expand and become rigid. Note also the "I-beam" like structure. The erect penis is incredibly resistant to pressure, and can apparently withstand pressures up to 6000 torr.

The penis pump, by creating negative pressure around the penis, causes blood to flow into the cavernosum and spongiosum resulting in an erection. Blood is then prevented from flowing back out by placing an elastic ring or band around the base of the penis. This treatment is effective more than 90% of the time, and works no matter what the cause of erectile dysfunction with some rare complications related to using excess pressure (cysts or blisters) or accidentally getting the scrotum or testes in the vacuum chamber. Osbon cornered the market, and made a huge difference in many men's lives.

The next major innovation, was implantable inflatable devices or bendable metal implants that allowed the patients to physically inflate the penis to create an erection. They look something like this.

This was, as you can imagine, a far more invasive treatment, but still had a high rate of patient satisfaction (amazingly).

But what was still missing was a medical treatment for erectile dysfunction. The discovery of the first such treatment was an accidental observation. Patients being given a drug paparevine during surgery to lower blood pressure were observed to get spontaneous erections. The obvious thing to do, for surgeons anyway, was to then see what happened when papaverine was injected directly into the penis. The results were revolutionary. But not appreciated until what was likely the most outrageous scientific presentation of all time. A British physiologist named Giles Brindley decided to present the results of his study of intra-cavernosal papaverine injections to the 1983 Urodynamics society in Las Vegas.
His method of communication of this discovery has since become infamous. A witness of this extraordinary presentation, Laurence Klotz, communicated his experience in the journal BJU International:

The lecture, which had an innocuous title along the lines of 'Vaso-active therapy for erectile dysfunction' was scheduled as an evening lecture of the Urodynamics Society in the hotel in which I was staying.








Professor Brindley's presentation was, however, enormously effective in convincing the urologists in attendance of the success of the treatment. Injection of papaverine was revolutionary, and helped scientists discover new insights into the molecular physiology of erection as well as providing a highly efficacious, if somewhat scary, treatment for erectile dysfunction. A papaverine-induced erection would typically last 1-2 hours and the treatment could be safely used once a day, about 3 times a week. The main complication was priapism.

But that's not the end of the story of course. The last great revolution in treating erectile dysfunction was removing the frightening prospect of using a needle to generate a medical erection.
Everyone knows about the little blue pill, and Viagra (Sildenafil), is of course one of the most widely-recognized brands in the world. However, it's discovery was equally unanticipated.

Smooth muscle is largely responsible for maintaining blood pressure by contracting or relaxing your blood vessels, thus increasing or decreasing blood pressure.
i-2928b758e3e6b25069f7067abb91fb0a-SMC Relaxation.jpg
Pfizer was investigating a drug named "UK-92480" that they had discovered by rational drug design. It caused smooth muscle relaxation through inhibition of the phosphodiesterase (specifically PDE5), which is responsible for hydrolysis of cyclic GMP. It was hoped that inhibition of PDE5 would cause smooth muscle relaxation via the pathway above, and lower blood pressure in patients. Unfortunately, results were modest. An interesting side-effect of the drug was noticed by male patients however, and the drug was surprisingly popular among the study participants despite the poor control of blood-pressure. Pfizer, not being idiots, realized they had hit gold. Finally, a treatment for erectile dysfunction in pill form had arrived.

Viagra is not 100% effective though, and some of the old-line treatments that work in patients that tend to be resistant (like diabetics with hypertension) are still in use. Further, it is completely ineffective in women. The reason is captured in the highly scientific chart below:
i-08855add6bdcfad00932a14d749ad9c3-Male vs Femal Sexuality.jpg
I shamelessly replicated this after seeing a similar one in a lecture last Friday (it was sex day - a series of lectures on taking sexual histories, sexual dysfunction, and treatments). Men are pretty simple when it comes to creating sexual desire. Even if the problem is lack of interest or desire, if you give a man an erection, he wants to stick it somewhere. I realize this is simplistic, but for the most part, bypassing desire and going straight to arousal solves the problem in us.

Women, however, are not primed for sex by mere engorgement of their sex organs. As a result, a simple pill treatment for lack of female desire has not been forthcoming. Although, I hear, a trial is underway to study the "love-patch" which contains - guess what? Testosterone!

We've come full circle - starting with testosterone as the treatment for female sexual dysfunction. The patch is probably ineffective or it likely would have been approved more rapidly. But maybe, after 100 years, we'll eventually figure out the female counterpart to Viagra.

I'd like to thank Dr. Ray Costabile for providing the inspiration for this post in the excellent lecture he gave us medical students this last Friday. His lecture was a large part of the source material, and his advice on sources for this post was invaluable.

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Wicked post. Brindley showed some pretty serious dedication to experimentation.



My office-mate is wondering why I'm creased up on the floor gasping for breath ...

I think that you guys are a goddamn bunch of preverts.

Professor Brindley called on every bit his psychiatric expertise when he labeled the screaming ladies in the front row as being filled with penis envy.

By gerald spezio (not verified) on 15 Oct 2007 #permalink

Why don't you check out this blogsite for a funny quote on Cialis and genetics by Dr. James Watson!

You will need to go below the fold to see the quote, though.

Very close yes, the lecturer in our course had clearly replicated that one as well with slightly different images, but she re-labeled it "male vs female sexuality" since she was doing an overview of the process of sexual arousal in men vs. women.

It was an interesting day.


For some, longer than others....


Dr. Brindley may have been operating under the assumption that 'what happens in Vegas, stays in Vegas'. Nice post.


I wonder who they found to test that.

Jenna Jameson has performed some tests and concluded that science can be fun.


I seem to recall seeing something about testosterone supplements in women. I think it was the Discovery (BBC?) series about human sexuality.

Anyway, a female sexologists had tried a testosterone injection on herself and reported how it had made her feel - and I quote (I think) - "horny for days after".

Somewhere in the back of my mind stirs the idea that this is a common complaint from FtM transsexuals,too, when they begin their hormone-therapy.

I may of course be completely mistaken.

It may have an effect in some women, but remember, the issues are complex and might be placebo related. Treatments for female sexual desire have a placebo rate of about 50% (sildenafil actually showed decreased efficacy compared to placebo).

As far as the pressure studies, they apparently were done in cadavers.

Outstanding post.

I may be able to add some information about Professor Brindley. I became interested, for reasons that now elude me, in Giles Brindley about this time last year. Most importantly, although there are numerous reports of his Las Vegas presentation, the one by Klotz is clearly the most convincing and least histrionic.

Brindley was indeed a physiologist and, moreover, a prodigious scholar who, while working primarily at the London Hospital and the University of London, published over 100 physiological research papers, especially in the areas of visual, genitourinary, sexual, and perceptual functions.

But there is more. After reviewing numerous internet sites, I found plenty of references to Giles Brindley - the physiology researcher and a fair number pertaining to Giles Brindley - the musician who composed and who developed the logical bassoon "which aimed to improve intonation and evenness of tone through use of electrically-activated key combinations that were too complex for the human hand to manage." I did not, however, find a single source that confirmed that both sets of accomplishments accrued to the same individual.

That matter was settled by an email response from Dr Brindley himself, which read in part, "I did compose "Variations on a Theme by Schoenberg," performed at the Spitalfields Festival in 2004, "Tyrolean Suite" for wind quintet, performed at the opening of the British Library in 2002, "the Waterman's Daughter" for soprano & woodwind quartet, and other pieces for chamber ensembles. I was Director of the Medical Research Council's Neurological Prosthesis Unit from 1968 to 1992. Music was my hobby until I retired, and my career since."

Anyway, I have a post on Giles Brindley with photos (not photos of his presentation) at Giles Brindley: Presentation Is (Not Really) Everything.

One final point: Dr. Brindley was 57 at the time of his Las Vegas performance, an auspicious age that I reached during the preparation of this post. Upon reflection, I felt inspired and even stirred.

I am a master of all those knobs, dials, and switches on the female sexuality panel, and only three or four of those require the single male sexuality switch be in the on position, I'm quite a few years younger than the boomers, so should the need ariseI will have agreat deal of resources at my disposal that have already been tried out on the boomers.

The "amazing" results of penile implants are an example of thorough, painstaking engineering. I was an engineer working with the inventor of the penile prosthesis, Dr. F Brantley Scott, at American Medical Systems from 1978-1984. The device pictured uses components that I designed with the good Dr., and it warms my heart to see them pictured here.

It was quite exciting to work in the ED biz, because the patient testimonials could be so moving, giving one a real sense of purpose in life, despite the jocularity usually accompanying discussions of ED treatments.

Nowadays, my main job is helping companies acheive high levels of excellence in medical device product design and development. I am specialized in cardiovascular devices,an area where there has been much recent news regarding the lack of quality of some devices. Let's all hope and work toward assuring that these devices are the best they can be!

the logical bassoon

For no reason I can explain, that name fills me with delight.

So what happened in Vegas didn't stay in Vegas.

By truth machine (not verified) on 21 Oct 2007 #permalink