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The Path of Protection

Study finds progestin in birth control pills appears to protect against ovarian cancer

WEDNESDAY, Jan. 9, 2002 (HealthDayNews) -- Doctors have long known that oral contraceptives can reduce the risk of ovarian cancer, but no one has understood why.

Now, a new study says the protection could be linked to the pill's level of progestin, a synthetic form of the hormone progesterone.

The higher the level, the researchers suggest, the greater the protection.

"It was always believed that birth control pills prevented ovarian cancer by limiting ovulation which, in turn, reduced potential DNA damage to the ovaries," says study author Joellen Schildkraut, an epidemiologist at Duke University and the Duke Comprehensive Cancer Center.

"Our study shows that there may be another component involved in the protective action, and that it could be the level of progestin found in a pill's formulation. We believe progestin is what affects apoptosis, or cell death. And this, in turn, is what helps reduce the risk of cancer," says Schildkraut.

All cells go through a normal life cycle, one that ends with cell death. The dead cells are replaced by new cells, and the life cycle of the human body continues.

But when a cell doesn't die, it continues reproducing itself. When enough of these renegade cells accumulate, a tumor develops, setting the stage for cancer.

For Dr. Steven Goldstein, Schildkraut's theory of progestin's protective value is interesting but inconclusive.

"The idea that there could be a second avenue by which the pill confers protection is intriguing. But right now, it seems to be a giant leap of faith linking that protection to levels of progestin," says Goldstein, a professor of obstetrics and gynecology at New York University Medical Center.

The Duke research isn't strong enough to draw any conclusions, he says, except that it's worth further investigation.

"I would not, for example, advocate any woman to select a [birth control] pill formulation based on progestin content, solely for the purpose of reducing her risk of ovarian cancer," Goldstein says.

Another reason for Goldstein's lack of excitement about this study: The Duke research involved pill users from as long as 20 years ago or more. Many of the pills used in the research contained levels of hormones so high they'd be considered unsafe by today's standards.

"Most of these formulations are no longer available, so it's hard to draw any relevant correlations to the formulations being used today," says Goldstein.

The Duke study looked at 390 women between the ages of 20 and 54 who had used oral contraceptives for three years or more. Many had used the pill 20 or more years ago. All the women were selected from the larger Cancer and Steroid Hormone Study, and all had been diagnosed with epithelial ovarian cancer. They were compared to a control group of 2,865 cancer-free women from the same age group.

Participants were divided into four groups based on the following pill formulations: high progestin/high estrogen; high progestin/low estrogen; low progestin/high estrogen; and low progestin/low estrogen.

The final result: Those women who took birth control pills containing the lowest levels of progestin had more than twice the rate of ovarian cancer as those who took high progestin pills, even when the estrogen contents were similar.

Additionally, those women taking the low progestin/low estrogen combination were 60 percent more likely to develop ovarian cancer than women taking the high progestin pills.

And women who did not use oral contraceptives were at greatest risk -- nearly three times more likely to develop ovarian cancer than those taking the high progestin pills.

"If it had just been birth control pill use alone that reduced the cancer risk, as was thought before, then clearly, the numbers would be the same or similar in each group. And that is not what we found," says Schildkraut.

It's important to note that at least one previous study found no difference between levels of progestin and protection from ovarian cancer, indicating that all pill formulations yield equal results.

While Schildkraut says the Duke findings dovetail with earlier animal studies that found similar results, she's cautious to suggest that all women seek out a high progestin pill just to gain cancer protection.

"Women at highest risk for ovarian cancer are often at equally high risk for breast cancer, harboring the BRCA 1 and 2 breast cancer genes. And progesterone increases the risk of breast cancer," says Schildkraut. High progestin pills could do these women as much harm as good, she notes.

Her hope: The new research will spurn the development of a "designer progestin" -- a drug that encourages cell death while discouraging breast cancer.

The study appears in the January issue of the Journal of the National Cancer Institute.

What To Do: For more information on ovarian cancer, visit The National Institutes of Health. You can also find the latest data on clinical trials involving ovarian cancer patients, as well as information on support groups, at the Ovarian Cancer National Alliance.

SOURCES: Interviews with Joellen Schildkraut, Ph.D, epidemiologist and researcher, Duke University's Department of Family and Community Medicine and the Duke Comprehensive Cancer Center, Durham, N.C.; Steven Goldstein, M.D., professor, obstetrics and gynecology, New York University Medical Center, New York City; January 2002 Journal of the National Cancer Institute
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