The estrogen component of oral hormone replacement therapy around the time of menopause is associated with ovarian cancer risk, findings from a Danish study show.

“Our results imply that the risk increases with cumulative oral estrogen intake but not with duration of hormone therapy,” the investigators report.

This suggests that the increased ovarian cancer risk associated with oral hormone therapy may be “diminished substantially” by minimizing the daily dose of estrogen from oral hormone therapy, Dr. Eva Glud from the Danish Cancer Society in Copenhagen and associates report in the Archives of Internal Medicine.

It has long been known that hormone replacement therapy is a risk factor for breast and endometrial cancer, as well as coronary heart disease and stroke, but the association with ovarian cancer is less clear, the team points out.

To investigate, they analyzed hormone therapy use in 376 ovarian cancer patients between the ages of 35 and 79, who had not undergone hysterectomy and 1111 healthy women of the same age. The cumulative intake of estrogen among women who had ever used oral hormone therapy ranged between 0.04 to 41.1 grams.

Higher cumulative oral intake of estrogen significantly raised the risk of ovarian cancer, the researchers report. According to the team, they observed a “simple trend” such that each additional gram of estrogen was associated with the same relative increase in risk of ovarian cancer.

After accounting for established risk factors, the team found that this corresponded to a 31 percent greater risk for every 5 grams of estrogen.

The risk of ovarian cancer did not increase with the duration or the cumulative intake of progestogen component of hormone therapy.

Clearly, the oral intake of replacement estrogen “should be diminished whenever possible,” the authors conclude.

Moreover, they suggest that if hormone therapy is prescribed simply for irregular bleeding before and around menopause, “treatment with progestogen only may be preferable.” On the other hand, “if an estrogen component is required for alleviation of menopausal symptoms, then the lowest possible daily dose should be used.”

SOURCE: Archives of Internal Medicine, November 8, 2004.