Do you remember the golden age of sports? I'm not talking about the days when athletes were heroes and played for the love of the game. I'm referring to the time when you could watch a three-hour football game without suffering through a dozen commercials (each dripping with unfortunate double entendre) for anti-impotence drugs.

Unfortunately, those days are long behind us, and sports fans should brace themselves for a full-fledged erectile dysfunction battle royal. Pfizer's (NYSE:PFE) Viagra, the reigning King of the Ring, weighs in with yearly sales of $1.74 billion. The main challenger is currently Levitra (luh-VEET-rah), a collaboration between GlaxoSmithKline (NYSE:GSK) and Bayer (NYSE:BAY) that was approved in August. A third challenger, Eli Lilly (NYSE:LLY) and ICOS' (NASDAQ:ICOS) Cialis (see-AL-is), was just approved last Friday, and will join the melee in late December.

The prize? A slice of the erectile dysfunction (ED) market, which is predicted to reach $6 billion by 2007.

The miracles of science
Logically, you'd think that the winner of the erectile Olympics would be the safest and most effective drug. However, all three of our contestants have the same mechanism, as they block the actions of PDE-5. This does not mean that the drugs are identical -- a closer look at how the medicines work reveals key differences between them.

In healthy individuals, the body's circulatory system acts as a highway that allows for the delivery of oxygen and nutrients and the removal of toxic wastes from organs and tissues. If the demands of the body increase, blood vessels release nitric oxide. Nitric oxide precipitates a reaction that results in the creation of cyclic guanosine monophosphate (cGMP), a molecule that leads to an increase in circulatory capacity by dilating blood vessels. In other words, when traffic starts to build, cGMP quickly adds two lanes to a four-lane highway, allowing key molecules to get home in time for dinner. Think about that on your rush-hour ride home from work. Just like the traffic, these highways don't last forever. An enzyme known as phosphodiesterase (PDE) breaks down cGMP, which causes vessels to contract and returns the body to its normal state. Got it?

Pharmaceutical companies quickly targeted the modification of these pathways as a way to improve flow and treat coronary artery disease. They hoped that blocking the effect of PDE would allow heart vessels to open wider, providing a treatment for angina and reducing the likelihood of heart attacks. Viagra, one of the first PDE blockers, was an early disappointment for Pfizer, as it was only minimally successful in treating angina. However, researchers were surprised at one side effect that popped up (groan -- if drug companies can make the jokes, so can I). It turned out that there are different types of PDE in the body, and Viagra blocks PDE-5, which is expressed in the groin. This results in increased dilation of the vessels in the penis, which enables male patients to create and maintain an erection.

Sizing up the candidates
Okay, enough of this alphabet soup. We understand the science, but if Viagra, Levitra, and Cialis all work on PDE-5, why aren't they the same? Small differences in the chemical behavior of these drugs give each of them a unique speed of onset, length of action, and side effect profile. In an ideal world, the perfect medicine would work instantly, last for a long time, and not have any side effects. Then again, in an ideal world we wouldn't have erectile dysfunction, so let's take a closer look at these drugs.

Of the three, Viagra has the weakest profile. Viagra needs to be taken on an empty stomach, and takes between 30 minutes to an hour to start working. Once active, its effects last for four hours. In contrast to popular opinion, that doesn't mean that you'll have an erection for four hours. Instead, if you are sexually stimulated during that time frame, Viagra will help create and sustain an erection. Also, even though Viagra is a relatively safe drug, its effects on another PDE (PDE-6) allow for a number of potential side effects, including temporary changes in vision, headaches, and flushing.

Levitra provides only a slight improvement to Viagra. It can be taken with food, only takes 25-30 minutes to take effect, and lasts up to five hours. Levitra has many of the same side effects as Viagra (including vision changes), but with a lower incident rate.

Cialis has the potential to render the other two drugs obsolete. Much like the T-1000 in Terminator 2, Cialis can do everything its predecessors can do, only faster and more effectively. A dose of Cialis (even when taken on a full stomach) takes as little as 16 minutes to begin working, and a single pill can have an effect for up to 36 hours. Cialis' long duration of action has reduced the need for planning around sexual activity, and has earned the drug the affectionate title of "Le Weekend" by the French. Furthermore, Cialis lacks the visual side effects of Viagra, but interacts with PDE-11, which causes temporary back pain in approximately 5% of users.

These advantages have made Levitra and Cialis popular in Europe. A study of 150 patients in Germany showed that 45% preferred Cialis, 30% Levitra, and 13% Viagra. Another study, from Cologne, showed that 43% of men preferred Levitra, 40% Cialis, and 17% Viagra. This popularity has translated into lower market share for Viagra. In Germany, one of the largest markets where all three drugs have been approved, Viagra only maintains 56% market share, with Cialis and Levitra at 30% and 14% respectively. In the U.S., pressure from Levitra has reduced Viagra's market share to a still-formidable 85%.

The Mickey D's Principle
Despite the media blitz surrounding the newer drugs, reports of the little blue pill's demise are greatly exaggerated. Call it the McDonald's (NYSE:MCD) Principle: If you ask around, people will agree that most restaurants make better hamburgers than McDonald's. But the next time you're on a trip, even when you have a choice of newer restaurants, chances are you'll stick with Mickey D's. Why? People (including physicians) like to stick with what they are familiar with. This idea becomes even more important when prescription drugs are involved.

Sure, some people will switch from Viagra to Levitra or Cialis. But for the most part, if patients are happy, they probably won't risk changing drug regimens. Furthermore, physicians are much more likely to prescribe drugs they are familiar and comfortable with. Viagra has had a five-year head start in proving its safety and effectiveness and in advertising these facts to physicians. Although physicians' prescribing practices will change as additional studies are conducted, the brand name, image, and sales force of Viagra will be incredibly difficult to overcome. It's not exactly Warren Buffett's castle with a moat around it, but it's pretty close.

The most likely scenario will have the overall market for ED expanding to allow all three drugs to achieve blockbuster (over $1 billion in annual sales) status. It is believed that roughly 50% of men over the age of 50 suffer from occasional ED, yet only 15%-20% seek treatment. Although ED ads may be annoying, they do work, and many more men will seek treatment.

And the winner is...
The gold medal should go to Cialis, and the silver to Levitra. Shareholders for GlaxoSmithKline, Bayer, ICOS, and Eli Lilly have already prospered from the buzz around these drugs, and each of these stocks is hovering around their 52-week high. Of these companies, ICOS and Lilly should have the biggest effect from the drug. ICOS is burning cash, and with revenues of only $92.8 million, Cialis should be a big boost (and a potential lifesaver). Lilly has revenues of $11 billion, and has been looking for its next blockbuster for a while. In contrast, GSK and Bayer each have revenues over $30 billion. Although additional sales might be a small boost, they won't have as large of an impact as they will at ICOS and Lilly.

On the losing end we have Pfizer and Viagra. Viagra should continue to bring big dollars in for Pfizer, but the increased competition will increase marketing costs and slow growth, decreasing the overall profitability of the drug. It is important to remember, however, that Pfizer has eight blockbuster drugs that prop up an annual revenue of $32 billion, so changes in sales of Viagra will have more of a psychological effect on shareholders than a substantial effect on business. Foolish investors who seek to add Pfizer to their portfolios should keep a close eye on the company in case it falls on Viagra-related news.

Unfortunately, the biggest loser in this battle must be Mr. Russell Cialis of Great Britain, whose request to Lilly and ICOS to change the name of their drug was unheeded. Cialis, who feared that younger members of the family would be ridiculed, has probably heard every joke in the book by now. All of us here at the Fool would like to wish Mr. Cialis and his family good luck in overcoming the laughs that will be had at their expense over the next 30 years, and we hope that they're able to come up with at least a few good comebacks.

Arash Mostaghimi, a guest writer for The Motley Fool, is a student at Harvard Medical School. He also runs a tutoring company in Boston, Arash wonders why Johnson & Johnson doesn't fulfill the destiny of its name and enter the ED market. He enjoys receiving feedback (and good jokes about Viagra) via email.