Ovarian cancer: homing in on the true risks.

One in 70 U.S. women will develop ovarian cancer, and more than 60 percent of them will die of their malignancy within five years of diagnosis. Clinicians have observed that childbearing and use of oral contraceptives tend to lower a woman's risk of this generally silent killer, while infertility and age have been linked to increased risk.

Now new analyses substantially revise that list of risks and previously tendered explanations of the cancer's likely biological cause.

The new findings could have important public health implications, asserts Carolyn L. Westhoff, an epidemiologist at Columbia University in New York City 

who is familiar with the analyses.

For instance, she points out, 80 percent of American women now take birth-control pills for an average of four years -- usually by age 30. That suggests, Westhoff says, that "we could get rid of half of this disease simply because women take the pill." Moreover, she argues, one newly identified possible risk -- drugs that trigger ovulation -"is a big enough deal to recommend against egg donation by healthy women" to infertile women. Until now, Westhoff notes, many physicians viewed these fertility-enhancing drugs much like vitamins: "They might help; can't hurt."

Alice S. Whittemore, an epidemiologist at the Stanford University School of Medicine, headed a team of researchers from 14 medical institutions who reviewed ovarian cancer data from 12 previous studies. Their series of four papers in the just released Nov. 15 AMERICAN JOURNAL OF EPIDEMIOLOGY examines Ovarian cancer risk factors among the studies' 6,500 white subjects - roughly one-third of whom had the cancer. In the Jan. 20 JOURNAL OF THE NATIONAL CANCER INSTITUTE, a fifth paper by the group focuses on the ovarian cancer risk among a much smaller group of black women who had taken part in seven of the studies.

Overall, Whittemore notes, her groups statistical review using meta-analysis turned up several new findings. Though physicians had known for some time that childbearing reduces ovarian cancer risk, the new study suggests that this protection is not just some fixed amount associated with reproduction. Rather, the birth of each successive child further reduces a mother's ovarian cancer risk, typically by 14 percent. Moreover, the larger analysis of white women showed, failed pregnancies -- miscarriages, elective abortions, and stillbirths -- also protect. Indeed, Whittemore told SCIENCE NEWS, per month of gestation, failed and successful pregnancies "seem to offer similar protection."

The analyses also found no increased risk linked to infertility per se. However, Whittemore said the apparent 27 times greater than expected incidence of ovarian cancer observed among white women taking drugs to enhance fertility came as "quite a surprise:' While the actual risk figure may not be reliable, owing to the small number of women involved, the disturbing trend not only appears reliable, she notes, but also biologically plausible. Previous studies have indicated that excessive ovulation or high levels of the hormones that trigger ovulation may foster ovarian cancer. Fertility drugs increase both.

In fact, Whittemore notes, her group for the first time neatly ties ovarian cancer risk to both high rates of ovulation and ovary-stimulating hormones.

The two findings that a woman's age at menopause did not affect her cancer risk and that oral-contraceptive use offered less protection in younger women were "the first thing that struck me as being of fundamental importance," adds Malcolm C. Pike of the University of Southern California School of Medicine in Los Angeles.

Why? It argues against ovulation as being the sole cause of this cancer. Pike says it also suggests that newer birth-control pills, which stop ovulation but don't lower levels of ovary-stimulating hormones, may prove far less effective than early pills in cutting ovarian cancer rates.