Estrogen Protects Women’s Brains Prior to Menopause

Mayo Clinic researchers have shown that women who had one or both ovaries removed before menopause faced an increased long-term risk of Parkinson’s disease and of several related conditions known as parkinsonism, compared to women who retained their ovaries. To protect against these conditions, estrogen replacement therapy may be warranted for women who had their ovaries removed before menopause. Ovaries are responsible for estrogen production. This study, the largest of its kind, appears in the Aug. 29 online edition of the journal Neurology, the medical journal of the American Academy of Neurology.

While further studies are needed to validate these findings and clarify their clinical implications, this Mayo Clinic research is among the first to suggest that there is an age-related therapeutic window of opportunity for estrogen replacement therapy.

Before age 50, estrogen replacement therapy may, in fact, be beneficial for the brain function of women who have their ovaries removed. This large study involved reviews of medical records and follow-up interviews with approximately 4,600 women.

Significance of the Mayo Clinic research

Prior to this Mayo Clinic report, there was limited or conflicting clinical and epidemiological evidence about estrogen’s ability to protect brain functioning in women - referred to as neuroprotection. The Mayo research results show that not only did women who had one or both ovaries removed before menopause have an increased risk for Parkinson’s disease or parkinsonism compared to other women, but that the risk increased the younger the woman was at ovary removal.

“The decision to remove the ovaries for a benign ovarian disease or for the prevention of ovarian cancer, and the decision to take estrogen treatment for a number of years after the removal of the ovaries, must be individualized for each woman,” explains Walter Rocca, M.D., a Mayo Clinic neurologist, epidemiologist and lead author of the study. “The surgery has expected advantages and disadvantages. Our findings support the concept that there is a window of therapeutic opportunity before the approximate age of naturally occurring menopause, 50 to 55, when the benefits of neuroprotection outweigh the risks of side effects of estrogen therapy.”

Based on the results of other studies, the Mayo Clinic researchers also say that after age 55 or 60 the balance of advantages and disadvantages from starting estrogen treatment is still somewhat uncertain, and the risk of side effects, such as increased cancers or strokes, from estrogen therapy may increase progressively with age. “There is strong evidence from other studies that starting treatment with estrogen after age 60 to 65 is not recommended,” Dr. Rocca says.

Implications for Patient Care

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.” says Bobbie Gostout, M.D., a Mayo Clinic gynecological and obstetrical surgeon. “When oophorectomy (ovary removal) is indicated in a young woman, it is important to carefully educate her regarding estrogen replacement. Unless clear contraindications are present, most women should be advised to start estrogen therapy after the surgery and to continue it until approximately age 50 if the ovaries must be removed.”

Dr. Gostout adds that a more challenging situation arises when only one ovary has to be removed in a young woman. “Traditionally, we’ve taught that the remaining ovary compensates in hormone production,” Dr. Gostout says. “The findings in this study tell us to carefully monitor such women for signs of low estrogen, but as of yet we don’t know when and how to compensate for the hormone changes when a single ovary is removed.”


Ovaries are the organs that secrete the female hormone estrogen, which naturally declines at menopause. For many years women were routinely prescribed estrogen replacement therapy to ease the symptoms of menopause. This practice changed around 2002–2003 when studies linked estrogen replacement therapy with increased risk of cancers and stroke. The most widely quoted study on this topic involved women with an average age of 63 when they started estrogen therapy. Now, with this Mayo Clinic report, the understanding of estrogen’s effects on women’s brain functioning is clearer, and estrogen replacement therapy may be indicated in younger women who require ovary removal.

About the Study

Mayo Clinic is home to the Rochester Epidemiology Project, which has collected medical records since 1935, and is one of the largest long-term integrated databases of patient records in the world. The Mayo Clinic team used the database to identify all the women in Olmsted County, Minn., who had one or both ovaries removed - approximately 2,300 - from 1950 through 1987. These women were matched by age with an approximately equal number of women who did not have ovarian surgery. Researchers then interviewed women in both groups (or their relatives if the women had died), examined those women who were suspected of having Parkinson’s disease, and reviewed their medical records to compare the risk of Parkinson’s disease or parkinsonism between the two groups, throughout their full life spans.

About Parkinson’s disease

Parkinson’s disease is a chronic, progressive movement disorder typically seen in people over age 50. The disease affects approximately two in 100 people. The diagnosis of Parkinson’s disease requires the presence of at least two of the following symptoms: tremors while at rest; rigidity of the muscles; loss of posture control; and slowed movements such as a slow gait. “Parkinsonism” describes patients who have some of these traits, but do not completely fit the disease criteria. Parkinson’s disease symptoms are caused by the death of or damage to key brain cells in the area known as the nigrostriatal dopamine system, which is involved in coordinating movements. The exact cause of the damage to that system is not known.

Collaboration and Support

The Mayo Clinic research team also included: J.H. Bower, M.D.; D.M. Maraganore, M.D.; J.E. Ahlskog, M.D.; B.R. Grossardt; Mariza de Andrade, Ph.D.; and L.J. Melton III, M.D. Their work was supported by grants from the National Institutes of Health; in particular, the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Source: Mayo Clinic

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