The Effects of Estrogen plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures

October 2003

Findings Summary

Gynecologic cancers are cancers of female organs other than the breast. We do not know much about the factors that affect these diseases, in part because they are not very common. Many years ago, a link between estrogen alone and endometrial cancer was found. Observational studies suggested that using estrogens combined with progestins would protect the uterus from this risk. Based on this information, physicians began to give combined hormones to women with a uterus.
In the October 1 issue of the Journal of the American Medical Association, the WHI investigators report that women randomized to combined estrogen plus progestin (E+P) experienced:
  • A 19% decrease in endometrial cancer rates
  • A 58% increase in ovarian cancer rates
Thus, women taking E+P have a risk of endometrial cancer that is similar to or slightly less than women taking placebo. Progestin appears to cancel the harmful effect of estrogen in the uterus, as previous studies showed. However, E+P does not completely prevent endometrial cancer, so the bleeding problems that women often have with this therapy must still be monitored. This monitoring usually includes doing an endometrial biopsy. In the WHI study, E+P use was associated with a 5-fold increase in the number of women needing endometrial biopsies.
The increase in ovarian cancer is consistent with reports from observational studies of estrogen alone and some other forms of combined hormones. However, the number of ovarian cancers in WHI was small (only 32), so it is possible that this was just a chance finding. No other study has linked this particular hormone combination with an increased risk of ovarian cancer. It is also helpful to think about these findings in another way. In women taking placebo, the rate of ovarian cancer would be 27 cancers per 100,000 women per year. In women taking E+P, the rate would be 42 cancers per 100,000 women per year, an increase of 15. Even if this effect of E+P is real and not a chance finding, ovarian cancer remains a rare disease in women taking these hormones.
The numbers of other gynecologic cancers (cancers of the cervix, fallopian tube, and peritoneum) were very small. Therefore, it is not possible to make conclusions about the effects of combined hormone use on these cancers.
Gynecologic cancers are rare diseases, so these estimates are not precise. Nevertheless, these results support current recommendations to use the lowest dose of E+P for the shortest duration needed to treat menopausal symptoms.