Estrogen protects women's brains prior to menopause

In the largest study of its kind, Mayo Clinic researchers have shown that women who had one or both ovaries removed before menopause faced an increased long-term risk of cognitive impairment or dementia, compared to women who retained their ovaries.

However, women who had both their ovaries removed but were treated with estrogen until at least age 50 did not have any increased risk. The study, which includes follow-up for more that 30 years and interviews with nearly 3,000 women, will appear in the Aug. 29 online edition of Neurology, the medical journal of the American Academy of Neurology.

This research helps clarify questions about the health role of estrogen before the age of natural menopause and estrogen's ability to protect brain functioning. This study is among the first to provide significant epidemiological evidence supporting the neurological benefits of ovarian preservation in young women and the neuroprotective role of estrogen in younger women.

“This study is one of the first to obtain large-scale data about neurological diseases in women who had their ovaries removed,” explains Walter Rocca, M.D., Mayo Clinic neurologist, epidemiologist and lead author of the study. “Our findings will contribute to a better understanding of the advantages and disadvantages of removing the ovaries in young women. In addition, our findings suggest that there is a window of therapeutic opportunity for prescribing estrogen replacement therapy in women who undergo ovary removal before age 50. This window of opportunity is before the approximate age of naturally occurring menopause, when the benefits of neuroprotection are likely to outweigh the risks of side effects of estrogen therapy.” By contrast, other studies have shown that when estrogen treatment is started after age 60 to 65, the risk of heart problems, stroke and cognitive impairment or dementia is increased.

Research results also showed that the risk for cognitive impairment or dementia increased the younger the woman was at ovary removal. “Adverse results increased for women who were of a younger age at surgery, and were the same regardless of reason for ovary removal. Somewhat more surprising, cognitive impairment was observed even in women who had only one ovary removed,” explains Dr. Rocca.

The study may have important medical implications for women facing choices about ovary removal and estrogen treatment after the surgery.

“In every medical or surgical decision there is a trade-off between risks and benefits,” says Bobbie Gostout, M.D., a Mayo Clinic gynecological and obstetrical surgeon. “Therefore, a woman considering ovary removal should discuss these findings with her physician prior to the surgery to consider the long-term implications and the possible strategies for estrogen treatment following the surgery.

“In view of this new information, careful individualized counseling is necessary to help women make informed decisions. When oophorectomy (ovary removal) is indicated in a young woman, it is important to carefully educate that patient regarding estrogen replacement. Unless clear contraindications are present, most women should be advised to take estrogen therapy until approximately age 50,” explains Dr. Gostout.

Mayo Clinic is home to the Rochester Epidemiology Project, which collects medical records beginning in 1935, and is now one of the largest long-term integrated databases of patient records in the world. The Mayo Clinic team used the system to identify all the women in Olmsted County, Minn., who had one or both ovaries removed -- 1,489 women -- between 1950 and 1987.

These women were matched by age with an equal number of women who did not have ovarian surgery (1,472). Researchers then interviewed women in both groups (or their relatives) and compared the risk of cognitive impairment or dementia between the two groups, until the time of death. Women who were alive were interviewed in person and underwent a cognitive test over the telephone. For women who had died, a family member was interviewed.