"A hard man is good to find," goes the saying. Hardness, in this case, results from blood flowing into and engorging the spongy tissue of the penis: the more blood flow, the harder the erection. And increased blood flow comes about by relaxing blood vessels in the penis, a process known as vasodilation.

The trigger, always, is an aroused brain, which sends the rather unsexy signal to the penis, "Release nitric oxide!" That activates an enzyme which causes increased levels of cyclic guanosine monophosphate (cGMP), a messenger molecule that causes the muscles in the penis to relax, thus increasing blood flow, et voilà, an erection — everything else being equal. (If this sounds complicated, it is; three Nobel Prizes were awarded in 1998 to the researchers who figured out the complete mechanism of vasodilation.)

Everything else isn't always equal, however. The "good" cGMP (from the point of view of a guy hoping for an erection) can be rapidly degraded by the "bad" enzyme phosphodiesterase type 5 (PDE5), resulting in the erection signal from the brain being stopped in its tracks, to a greater or lesser extent. Greater, in this case, goes by the name of erectile dysfunction (ED), when the man isn't hard enough for intercourse, no matter how excited he feels. Physical causes of ED include heart disease, diabetes, side effects of drugs, neurological problems resulting from prostate surgery, and — most commonly — aging.

So the trick to counter complete or partial ED is to minimize the effect of PDE5 with (duh) PDE5 inhibitors. These include sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), three of the most financially successful drugs ever. Viagra, the first to be patented and marketed, was discovered by pure serendipity. The drug company Pfizer was studying what was then known as "UK92480" at its British facility in Kent (my home county) in the 1980s, hoping to find a treatment for angina (chest pain caused by constricted arteries of the heart). The drug didn't do much to counter angina, but had the unexpected side effect of dilating blood vessels in the penis (as male test subjects happily reported) — and thus was the "little blue pill" born.

The FDA approved UK92480, now named Viagra, in 1998, and the boom was on, with help from an advertising campaign whose aging shills included Bob Dole and soccer star Pelé. Today, annual worldwide sales of the drug are around $2 billion, with stiff competition, so to speak, from Cialis and Levitra, not to mention copycat pills and supposedly equivalent herbal analogs.

Since the Dole-Pelé endorsements, Pfizer's marketing approach has changed to appeal to younger men. According to a 2013 report in the Journal of Sexual Medicine, 25 percent of males now seeking medical treatment for ED are under 40. In addition, Gen Xers and younger are taking Viagra for what's called, in medicalese, "recreational use" (isn't it all recreational?), since the drug reduces something that goes by the coy name of "postejaculatory refractory time."

In any case, Pfizer and the other manufacturers of PDE5 inhibitors had better come up with a new audience fast, since their patents are about to expire. A generic version of Viagra will be available in two years' time; no word yet on what color it will be.

Barry Evans ([email protected]) believes, along with just about everyone who's thought about it, that the brain is the most important sex organ.