EPO: questions and answers on a banned drug

What is EPO?

EPO is the acronym for erythropoietin, a hormone that stimulates bone marrow to produce red blood cells. Everybody needs this hormone. However, it's not what got those riders kicked out of the Tour de France.

They were expelled for using a synthetic form of erythropoietin. The first drug of this type -- recombinant human erythropoietin, or rHuEPO -- became available in 1988, and in 1990 the International Olympic Committee put it on its "List of Prohibited Substances." It is also banned by the World Anti-Doping Agency and many sports federations.

A number of synthetic forms of erythropoietin now exist (all banned). They get much more press than the naturally occurring hormone and have pretty much co-opted the shorthand "EPO." From now on, we'll use EPO to refer to synthetic forms of the hormone, and "HuEPO" (for human EPO) to refer to the natural kind.

Why is EPO a "prohibited substance"?

It's considered a performance-enhancing drug.

If athletes aren't allowed to use EPO, why was it invented?

EPO serves important medical purposes. Some people don't have enough HuEPO. For instance, since HuEPO is primarily produced in the kidneys, people with kidney problems may not make enough. Also, chemotherapy may disrupt HuEPO production. But when people don't have enough HuEPO, they don't make enough red blood cells -- i.e., they become anemic. EPO was designed to help these patients.

Why do athletes think EPO is so great?

Muscles need oxygen to burn glucose to produce energy. The longer and harder they work, the more oxygen they need, and the faster they need it.

Red blood cells are the body's oxygen delivery system: They carry it throughout the body. When people are anemic, they get tired easily because their oxygen supply is impaired.

Elite athletes generally have a fine oxygen supply for everyday life. But those who compete at top levels requiring considerable endurance can benefit from having an extraordinary delivery system. For them, adding extra red blood cells -- to a point -- is like adding extra UPS trucks at Christmas.

Is it possible to have too many red blood cells?

Yes. Blood is essentially made up of red blood cells and plasma. The percent, by volume, that is made up of red blood cells is called hematocrit. In men, hematocrit levels usually range from 40% to 50%, and in women, 36% to 45%.

A body that's functioning normally can sense when it's experiencing an oxygen shortage, produce more HuEPO and thus raise its hematocrit. But it won't raise the level too high because the body knows when to say when.

But if people take EPO, "there's no natural shut-off," says Dr. Jordan Metzl, a sports medicine physician at the Hospital for Special Surgery in New York City. "The blood can get thick, like heavy motor oil."

High hematocrit levels can lead to high blood pressure, as well as clotting and even heart attacks and strokes.

The International Cycling Union doesn't allow riders to compete if their hematocrit is above 50%. Still, "a number of cyclists have mysteriously died in hotel rooms," says Dr. Allan Abbott, professor of family medicine and sports medicine at USC. "It's suspected they used too much EPO."