Estrogen tied to increased risk of ovarian cancer: some are questioning the study's design and incomplete data on family history. (44,241 Women Studied).

A new study deals yet another blow to hormone replacement therapy by suggesting that long-term use of unopposed estrogen is associated with a significantly increased risk of ovarian cancer, but some experts are questioning its conclusions.

Of 44,241 women followed for a mean of about 13 years, 329 developed ovarian cancer. The use of combination hormone replacement therapy (HRT) was not associated with ovarian cancer. However, the rate of ovarian cancer among women who had ever used unopposed estrogen replacement therapy (ERT) was 60% higher than in women who had never used ERT, representing a rate ratio of 1.6. The rate ratio was 1.8 in women who had been on ERT for 10-19 years and 3.2 in those on ERT for 20 years or more, reported James V. Lacey Jr., PhD., and his colleagues at the National Cancer Institute in Bethesda, Md.

Still, because ovarian cancer remains rare, the increased risk of the disease in ERT users would translate into only a small increase in the number of ovarian cancer cases. In this study, the incidence of ovarian cancer in women who did not use estrogen was 4.4 cases per 10,000 women-years, compared with 6.5 cases per 10,000 women-years in ERT users, Dr. Jan Leslie Shifren, director of the menopause program of the Vincent Obstetrics and Gynecology Service at Massachusetts General Hospital in Boston, said in an interview.

"So even if this association is found to be true, it would probably account for 12 cases per 10,000 women per year," said Dr. Shifren, who has received research funding from Eli Lilly & Co., Watson Pharmaceuticals Inc., Solvay Pharmaceuticals Inc., and Procter & Gamble Co., companies that make hormone replacement preparations.

The findings have also been called into question by Dr. Shifren and ...