Progestin enhances an anticancer process.

Taking birth control pills for a few years decreases a woman's risk of getting ovarian cancer later in life. With egg release stopped, the ovaries' outer lining undergoes less wear and tear, which scientists have theorized makes abnormal cell growth less likely.

Indeed, a woman who takes birth control pills for only 3 years--less than 10 percent of the typical 40 years of fertility--can lower her ovarian cancer risk by 30 to 50 percent, studies have shown. This surprising level of benefit led scientists at Duke University Medical Center in Durham, N.C., to suspect that the pills, besides preserving the ovarian lining, can trigger some process that actively thwarts cancer.

The researchers now find that cynomolgus macaque monkeys getting the hormone progestin had a high rate of programmed cell death in their ovaries. This process, called apoptosis, allows the body to dispose of cells damaged beyond repair--a function necessary to avoid aberrant cell growth that can lead to cancer. Disruption of apoptosis has been seen in other cancers.

The new findings indicate that progestin enhances apoptosis, which may explain some of the protection that birth control pills impart, says study coauthor Gustavo C. Rodriguez, a gynecologic oncologist at Duke.

The researchers gave 55 female monkeys oral contraceptives containing a synthetic version of the hormone estrogen, progestin, or both. Twenty other monkeys receiving no contraceptives served as a control group.

After nearly 3 years, ovarian lining from the monkeys getting the contraceptives that contained progestin showed significantly more apoptosis than tissue from the control group or the estrogenonly group. About 3.9 percent of ovarian cells in the control group and 1.8 percent of cells in the estrogen-only group were undergoing apoptosis, compared with 24.9 percent of cells in the progestin-only group and 14.5 percent in the monkeys getting a birth control pill containing both hormones, the researchers report in the September/October JOURNAL OF THE SOCIETY OF GYNECOLOGICAL INVESTIGATION.

"This is interesting, but it needs to be confirmed with more control animals," says Gabriel Nunez, a pathologist and molecular biologist at the University of Michigan Medical School in Ann Arbor. He notes that ovaries were taken from the control group at random times during the monkeys' ovulatory cycles, so the tissue samples presented a range of apoptotic cell counts, blurring the comparison.

Rodriguez notes that while the controls' apoptosis readings did range widely, most of these tissue samples came from monkeys in the phase of their monthly cycle that follows ovulation. The ovaries are then secreting a natural form of progestin called progesterone. Despite that, "we still see significantly more apoptosis in the monkeys that had received birth control pills with progestin," he says.

The new apoptosis data complements a theory that attempts to explain why 140,000 women die of ovarian cancer worldwide every year. Without contraceptive pills, the string of monthly ovulations in a woman's fertile years is usually broken only by pregnancy and breast feeding. These respites lessen ovarian lining damage. But as women have fewer children, they ovulate more times. The body repeatedly makes eggs, thrusts them out of the ovary, and then repairs the breach (SN: 7/5/97, p. 7).

"We're not doubting that this disruption and repair increases the cancer risk," Rodriguez says. However, he believes that progestin's ability to promote apoptosis in the ovarian lining could represent an additional protective effect of oral contraceptives against cancer.