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Adapted from the NCI Cancer Bulletin, vol. 4/no. 25, Sept. 11, 2007 (see the current issue). Women who had one or both ovaries removed before menopause for noncancer reasons faced an increased risk of developing cognitive problems or dementia later in life, according to a new study. But women who underwent estrogen replacement therapy until at least age 50 after having their ovaries removed were not at increased risk.
The study supports the hypothesis that there may be a "critical age window for the protective effects of estrogen on the brain," the researchers write in the September 11, 2007, issue of Neurology (see the journal abstract).
The study included nearly 3,000 women, who were followed for more than 25 years. Dr. Walter Rocca of the Mayo Clinic and his colleagues studied 813 women who had one ovary removed, 676 women who had both ovaries removed, and a comparison group of women who did not have their ovaries removed when the study began. About half the women had their ovaries removed because of a benign condition, such as cysts or inflammation; the others had their ovaries removed prophylactically to prevent ovarian cancer. Women who had the procedure for ovarian cancer or another estrogen-related cancer (usually breast cancer) were excluded because of their high risk of death shortly after surgery.
The researchers suggest three possible mechanisms to explain the association they observed. First, ovary removal may cause an estrogen deficiency that initiates biological changes leading to the elevated risk. Second, the association may involve a deficit of progesterone or testosterone rather than estrogen secreted by the ovaries. Third, the association may be caused by susceptibility genes that independently increase both the risk of ovary removal and cognitive impairment or dementia.
The study's strengths include the long follow-up and the fact that the women were representative of the general population. Its limitations include the use of telephone interviews to assess cognitive abilities and an overall interview participation rate of 62 percent. In addition, the surgeries were done between 1950 and 1987, when surgical practices and estrogen use may have differed from today.
Nevertheless, the findings should lead to a reassessment of prophylactic removal of the ovaries in premenopausal women and of the use of estrogen treatment following ovary removal, the researchers say. "The results of this study are important for the majority of women who do not have an increased risk of ovarian cancer," says Dr. Rocca. "Women should consult with their physicians when considering the risks and benefits of prophylactic removal of the ovaries, and when considering treatment afterwards."
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