The scientists followed 44,241 women for approximately 20 years. Compared to postmenopausal women not using hormone replacement therapy, users of estrogen-only therapy had a 60 percent greater risk of developing ovarian cancer. The risk increased with length of estrogen use. The women, who were followed from 1979 to 1998, were former participants in the Breast Cancer Detection Demonstration Project, a mammography screening program conducted between 1973 and 1980.

The relative risk for 10 to 19 years of use was 1.8, which translates to an 80 percent higher risk than non-users, and increased to 3.2 (a 220 percent higher risk than non-users) for women who took estrogen for 20 or more years.

Estrogen is a natural hormone produced primarily by the ovaries. After menopause, the ovaries produce lower levels of the hormones estrogen and progesterone. By the time natural menopause is complete – usually between ages 45 and 55 – hormone output decreases significantly.

As early as the 1940s, women began using estrogens in high doses to counteract some of the short-term discomforts of menopause (hot flashes, vaginal drying and thinning, and urinary tract incontinence and infections).

The trial, part of the Women’s Health Initiative (WHI), also found fewer cases of hip fractures and colon cancer among women taking the combined therapy. However, because overall the harm was greater than the benefit, the trial was stopped last week, three years ahead of schedule. The WHI randomized trial for estrogen alone in women who have had their uterus removed is continuing.

Anywhere from 20 percent to 45 percent of U.S. women take some form of hormone therapy between the ages of 50 and 75. According to industry estimates, about 8 million U.S. women use estrogen alone and about 6 million U.S. women use estrogen-progestin therapy. About 20 percent of hormone users continue for more than five years.