Do Fertility Drugs Cause Cancer?

For an infertile woman trying to get pregnant, the desire for a baby often overwhelms everything else. At the same time, the No. 1 fear of many Americans is cancer. So when a recent study in The New England Journal of Medicine reported that taking clomiphene -- one of the most commonly prescribed fertility drugs in the United States-may dramatically increase the risk of ovarian cancer, thousands of women were thrown into conflict. Which emotion should they heed? Is creating a new life worth jeopardizing your own?

Liz Tilberis, British-born editor of Harper's Bazaar, didn't have the agony or the luxury of such a choice. Tilberis, now 47, took fertility drugs in her 30s; they didn't work, and she and her husband adopted two boys, now 13 and 9. Last year she learned she had ovarian cancer, diag-nosed at a moderately advanced stage. Now, after aggressive chemotherapy, Tilberis says her doctors have pronounced her cured. It was a narrow escape: the survival rate for ovarian cancer is just over 41 percent, primarily because no test reliably detects it at an early, curable stage. Tilberis, who wrote in Harper's Bazaar about a suspected link between the disease and fertility drugs a month before the NEJM study appeared, has received more than 200 heartfelt letters from readers.

The lifetime risk of ovarian cancer is less than 2 percent, compared with 12 percent for breast cancer. A family history of the disease greatly increases the risk; a diet high in saturated fat may also play a role. For reasons not entirely clear, frequency of ovulation also seems to encourage malignantics. Clomiphene, like several other fertility drugs, is prescribed to stimulate ovulation; pregnancies and birth-control pills both suppress it, lowering the odds.

Other studies have suggested an association between clomiphene and ovarian cancer without demonstrating a firm causal relationship. According to Dr. Noel Weiss, an epidemiologist at Seattle's University of Washington School of Public Health and a coauthor of the new report, its findings "move the ball quite a bit forward in establishing a causal link." Women who took clomiphene for more than 12 menstrual cycles, he says, had a risk of ovarian cancer 11 times higher than usual. The drug's manufacturers recommend only three cycles; the American Fertility Society advises no more than six.

To some women, the possible risk of the drugs simply doesn't matter. "It's not my priority," declares Susan Cahn, 30, a Newton, Mass., retail manager who has just completed her 10th cycle of clomiphene. "Getting pregnant is my priority." She does, however, plan to pay extra attention to having her ovaries examined if she takes any more clomiphene. Judy Sachs Sullivan, 37, a museum educator from Belmont, Mass., took seven cycles of clomiphene even though there's a history of ovarian cancer in her family and she knew the medication might put her at still further risk. She had her ovaries examined with ultrasound (which does not necessarily detect early tumors) and took the new CA 125 blood test, which measures a protein often present in ovarian cancer but fails to detect many tumors. "You need to educate yourself about the drugs," Sullivan says, "but the risk can be worth it to have a baby."

Clomiphene is still being prescribed, sometimes with new caution. "Now there are enough studies to warrant this kind of attention," says Dr. Mark Sauer, a director of the University of Southern California's in vitro fertilization program. "But people shouldn't panic." Sauer believes the drug is safe to use for up to a year. One reason: there's been almost no increase in ovarian cancer cases since U.S. women--more than 2 million by now--began taking domiphene and similar drugs in the late 1960s.