Protective Effect Of Progestin In Hormone Replacement Therapy Appears to be Dose-Related

Dr. Shirley Beresford, associate professor of epidemiology,and Dr. Noel Weiss, professor of epidemiology, published resultsof their study in The Lancet on Feb. 15.

Taking estrogen after menopause can significantly reducewomen's risk of heart disease and osteoporosis, but sinceestrogen stimulates the growth of the endometrial cells, estrogenreplacement therapy can also increase the risk of endometrialcancer.

Although endometrial cancer is relatively rare -- even withthe increased risk associated with estrogen therapy -- andalthough it is usually curable, this side effect is cause forconcern. Therefore, many estrogen replacement regimens nowinclude taking a progestin at least several days a month.

To determine how well this strategy works and which dosingregimens are best, the researchers interviewed 832 women who hadhad endometrial cancer and 1,114 women who had not, about theirmedical history and use of hormone replacement therapy.

They found that women who took estrogen without also takingprogestin had a four-fold increase in risk of endometrial cancer,compared to women who had never taken hormone replacement therapyor had taken it for less than six months.

By contrast, there was only small increase in risk ofendometrial cancer in women who took progestin along with theirestrogen therapy.

"This apparent protective effect seems to depend a greatdeal on how many days a month the women took the progestin,"said Beresford. For women who took progestin for 10 days or twoweeks a month, there was no statistically increased risk ofendometrial cancer. But among those who took progestin for fewerthan 10 days a month, the risk was three times higher compared tonon-users.

"Women taking the combination therapy should be sure takeit for at least 10 days a month," said Weiss.

While cautioning that their results are preliminary, theresearchers also report evidence that the protective effect ofprogestin may diminish over the long term. They found that evenamong women who took progestin for 10 days or two weeks a month,those who took the combination therapy for more than five yearshad a 2.5 times greater risk of endometrial cancer compared towomen who had never taken hormones.

"This finding of increased risk associated with long useof estrogen combined with cyclic progestin therapy is new, andneeds to be replicated by other investigators," commentedBeresford.

The researchers also noted that their study does not provideinformation on women who take combined therapy every day of themonth.

"The risk of endometrial cancer is small, occurring inless than one woman in a thousand each year," said Weiss."Even with hormone replacement therapy, the risk remainssmall. The cancer is almost always contained in the uterus and isusually curable."

Co-authors of the study are Lynda Voigt, auxiliary faculty inepidemiology, and Barbara McKnight, professor of biostatistics.The research was funded by grants from the National CancerInstitute.