Postmenopausal women who use oestrogen replacement therapy for more than 10 years may be at increased risk of dying of ovarian cancer, a new study has found.
Dr Carmen Rodriguez and colleagues from the American Cancer Society in Atlanta, Georgia, looked at 944 deaths from ovarian cancer recorded over 14 years. Among the group, postmenopausal women who used oestrogen for at least 10 years were about twice as likely to develop ovarian cancer as their peers who did not take it. Even women who used oestrogen for 10 or more years but stopped taking it remained at risk 29 years later (JAMA 2001;285:1460-5).
Dr Rodriguez and colleagues followed nearly 212000 women for 14 years. About 22% had used oestrogen replacement therapy. Among women who had used the therapy for at least 10 years, the rate of death from ovarian cancer was 64.4 per 100000 women. This compared with 38.3 per 100000 women who discontinued oestrogen therapy after at least 10 years of use and 26.4 per 100000 women who never used the therapy. Using oestrogen for less than 10 years did not increase risk of developing ovarian cancer.
Postmenopausal use of oestrogen has already been associated with increased risk of hormone related cancers. The incidence of endometrial cancer increases rapidly with use of unopposed oestrogen; the incidence of breast cancer, however, increases only after long term use of oestrogen.
Although evidence exists that pituitary and sex hormones can cause ovarian cancer, epidemiological studies of the association between postmenopausal use of oestrogen and ovarian cancer have had inconsistent results.
The authors noted that the current findings may not apply to hormone replacement therapy that includes oestrogen in combination with other hormones such as progesterone. When the study began in the early 1980s, most women took only oestrogen and not a combination of hormones, which is what women take today.
“If the association is real—we have to wait for other studies—these results may be relevant for women with intact ovaries taking oestrogen for a long period of time,” Dr Rodriguez said. She recommended that women talk to their doctors about the balance of risk and benefits, based on their own health profile.
Exactly how oestrogen replacement therapy increases risk of ovarian cancer is not known. The principal endocrine change of menopause is a decrease in oestrogen secretion resulting from depletion of ovarian follicles, with consequent loss of negative feedback inhibition to the pituitary gland and transient increased levels of gonadotrophins.
Postmenopausal oestrogen therapy raises serum oestradiol and oestrone levels and decreases the secretion of gonadotrophins. In a previous study of the association between serum hormone levels and the development of ovarian cancer, decreasing levels of gonadotrophins were associated with significantly higher risk of ovarian cancer (JAMA 1995;274:1926-30).