Estrogen therapy linked to ovarian cancer

Source: Rodriguez C, et al. JAMA 2001; 285:1,460-1,465.

Rodriguez and colleagues from the American Cancer Society examined the association of postmenopausal estrogen use and ovarian cancer mortality in a prospective cohort study. The American Cancer Society Cancer Prevention Study II enrolled 676,306 postmenopausal in women using a baseline questionnaire in 1982. Deaths in this cohort through 1996 accounted for 107,810 (15.9%) of the original group. After exclusions (premenopausal, unavailable information, hysterectomy, ovarian surgery), 211,581 postmenopausal women were left for analysis, with a total of 1,497 ovarian cancer deaths.

Estrogen use (ever use, past use, current use) was based on responses to the baseline questionnaire. The risk ratio for ovarian cancer mortality was adjusted for age, race, oral contraceptive use, number of live births, body mass index, age of menarche and menopause, and tubal ligation. The statistically significant, increased adjusted risk ratios are presented in the table. (See Table 1, below.) These numbers indicated 64.4 ovarian cancer deaths per 100,000 users of estrogen for 10 or more years, compared with 26.4 for never users. Rodriguez et al further concluded that some risk persisted for up to 29 years after discontinuing estrogen. Rodriguez et al considered a possible mechanism for their conclusion, suggesting that ovarian cancer is more affected by lower gonadotropin levels than higher levels. (This would not be consistent with the protective effect associated with oral contraceptives, or that estrogen directly stimulates ovarian cellular proliferation).

Table 1-Risk Ratio for Ovarian Cancer Mortality
No. of Deaths Rate Ratio (similar to Relative Risk)
Ever use 255 1.23 (1.06-1.43)
>10 years of use 31 2.20 (1.53-3.17)