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OOPHORECTOMY MAY RAISE PD RISK

Laino, Charlene

ORIGINAL ARTICLE

MIAMI BEACH—Women who have had an oophorectomy are at increased risk for developing parkinsonism and Parkinson disease (PD) later in life, Mayo Clinic researchers reported here in April at the AAN Annual Meeting.

The diagnosis of PD requires the presence of at least three of the following – rest tremor, loss of postural control, hypomimia, and bradykinesia, among other clinical indications. Parkinsonism is the term used for people who have some but not all of these features.

“The risk is higher – about double – for women with both ovaries removed; however, even removing one ovary may increase the risk,” said Walter A. Rocca, MD, Professor of Neurology and Epidemiology and lead study investigator.

The culprit is not the procedure itself, Dr. Rocca said, but the subsequent drop in endogenous estrogen levels. Removal of the ovaries is the major cause of reduced estrogen during what would typically be considered a woman's reproductive years, he said.

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STUDY PROTOCOLS

The historical cohort study involved all 1,202 women who had had bilateral oophorectomy and all 1,283 women with unilateral oophorectomy from 1950 through 1987 in Olmsted County, MN.

For each woman who had surgery, the investigators selected a woman of the same age who did not.

The women were followed for an average of 25 to 30 years, through onset of parkinsonism or Parkinson disease, death, loss to follow-up, or time of the study analysis, Dr. Rocca reported.

Parkinsonism was detected in 24 women who had both ovaries taken out, 15 of whom had Parkinson disease. Nineteen women who had a unilateral oophorectomy developed parkinsonism; 10 had PD. Of the women who did not have surgery, 29 developed parkinsonism, 19 of whom had PD.

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“The findings were quite striking – more dramatic than we expected,” Dr. Rocca told Neurology Today.

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RISK DOUBLED WITH BILATERAL OOPHORECTOMY

For women who had bilateral oophorectomy, the risk of PD was double and the risk of parkinsonism was 80 percent higher, compared with controls. Both these values were statistically significant.

“For one ovary, the finding was a little less sharp, but even that may increase the risk of Parkinson disease or parkinsonism,” he said. Specifically, women who underwent unilateral oophorectomy had a 40 percent increased risk of Parkinson disease and a 60 percent increased risk of parkinsonism, compared with women who had no ovarian surgery, although neither value was statistically significant.

“We're trying to get funding to follow these women for five more years because we would expect to see more cases of parkinsonism as the women age,” Dr. Rocca said.

The new study is the first to directly link ovary removal and Parkinson disease, he said. “And ovary removal is the most direct surrogate for low estrogen stores.”

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ESTROGEN LINK TO PD

Stanley Fahn, MD, H. Houston Merritt Professor of Neurology and Director of the Center for Parkinson's Disease and Other Movement Disorders at Columbia University, said the estrogen connection is “intriguing.”

“The study fits with indirect evidence that estrogen itself might have protective effects against Parkinson disease,” he said.

Women are much less likely to get Parkinson disease, he said. “No one knew why. Was it diet? Smoking? We seemed to rule those things out and hormones came up.”

Dr. Rocca noted that there is biological evidence from animal studies that estrogen is protective for dopamine-producing cells in the substantia nigra.

Also, his own previous study showed that women with PD tended to have earlier menopause than women without the disease. They were also more likely to have had hysterectomies with or without unilateral oophorectomy, he said, (Mov Disord 2001;16(5):830–837).

And last year, Italian researchers reported a significant link between surgical menopause and other factors reducing estrogen stimulation during life and Parkinson disease, further supporting the hypothesis that endogenous estrogens play a role in the development of PD, he said (Neurology 2004: 62(11):2010–2014).

Based in part on all these studies, investigators are now looking at whether estrogen can be used as a treatment for some women with PD, Dr. Fahn said.

The Parkinson Study Group, under the direction of Lisa M. Shulman, MD, of the University of Maryland, is conducting the trial, dubbed POETRY (Parkinson's Disease on Estrogen Replacement Therapy in Menopause Years), to measure the safety and tolerability of two months of estrogen replacement therapy for postmenopausal women with Parkinson disease.

The study will also measure how estrogen replacement affects thinking and behavior, movement, and activities of daily living, as well as motor fluctuations and dyskinesias.

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ADVICE FOR PATIENTS

Dr. Rocca said that clinicians should advise patients who are thinking about preventive oophorectomy to weigh the new findings when making their decision.

Studies have shown that breast and ovarian cancer risk falls by about 50 percent after oophorectomy, a major consideration for those with a family history of the diseases. But the risk of osteoporosis and heart disease rises when the ovaries are removed.

Particularly since the advent of less invasive laparoscopic techniques, “many surgeons tell women who are having one ovary removed for a cyst or cancer that maybe we should just remove both.”

“Our data suggest that this is not a good idea, at least in terms of the brain,” Dr. Rocca said. “Pros [of ovary removal] include cancer prevention, but cons are your bone and brain health. The decision has to be made on a case-by-case basis.”

If a patient has a cyst in one ovary, for example, “look at other options,” he said. “Since they can be followed by imaging, maybe you can do only one ovary and monitor the other closely.”

For the minority of patients having cancer-ridden ovaries removed – which accounted for only about 100 of the approximate 2,500 women studied – the decision is unambiguous, he added. “If you have cancer in the ovary, you want to cut it out.”

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ARTICLE IN BRIEF

  • ✓ A new study is the first to show a link between ovary removal and risk for parkinsonism and Parkinson disease. Experts think the drop in endogenous estrogen levels may contribute to increased risk.
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REFERENCE

• Ragonese M, D'Amelio G, Salemi P, et al. Risk of Parkinson disease in women: Effect of reproductive characteristics. Neurology 2004: 62(11):2010–2014.
    ©2005 American Academy of Neurology