Oophorectomy Before Menopause Linked to Increased Risk for Dementia, Parkinsonism

Caroline Cassels

August 29, 2007

August 29, 2007 — Two studies conducted by Mayo Clinic researchers show that women who undergo unilateral or bilateral oophorectomy before menopause face a significant increased risk for dementia and parkinsonism compared with those who retain their ovaries or who have adequate postsurgical estrogen replacement therapy (ERT) until at least the age of 50 years.

In examining the association between oophorectomy and the risk for dementia and parkinsonism, investigators found that those who underwent the procedure before menopause had an almost 2-fold increased risk for both outcomes compared with those who did not have the surgery.

The findings were similar regardless of the indication for oophorectomy or whether study subjects underwent a unilateral or bilateral procedure.

"We found that women who had their ovaries removed early in life, clearly before menopause, had an increased risk for cognitive decline or dementia as well as parkinsonism. Furthermore, we found the younger the woman at the time of surgery, the greater the risk, so that there appears to be a stepwise increased risk associated with younger age," principal investigator Walter Rocca, MD, told Medscape.

Perhaps most striking, added Dr. Rocca, was the finding that women who had their ovaries removed but who received ERT until at least the age of 50 years returned to normal risk.

The studies are published online August 29 in Neurology.

Window of Opportunity

According to Dr. Rocca, these findings are the first to show there is a window of therapeutic opportunity for prescribing ERT in women who undergo oophorectomy before the of age 50 years.

This window, he said, occurs before the age of naturally occurring menopause, when the benefits of neuroprotection likely outweigh the risks associated with ERT.

In contrast, other research, most notably the Women's Health Initiative (WHI), has raised concerns about the potential detrimental effects of ERT.

Launched in 1997 to determine the impact of long-term hormone-replacement (HRT) therapy in postmenopausal women, the WHI was stopped in 2002 after it came to light that HRT significantly increased the risk for cardiovascular disease and ischemic stroke.

Since then, said Dr. Rocca, there has been a tendency by the medical community to interpret ERT as risky at all ages. However, he said, it appears from these results that estrogen has a protective, albeit age-dependent, effect.

"The Women's Health Initiative made the very clear point that initiating estrogen therapy after the age of 65 years to prevent neurological disorders is not advisable. Our study makes the point that if oophorectomy is indicated in young women, clinicians and patients should seriously consider ERT until at least age 50 years. The effects of ERT beyond age 50 years and before age 65 years remain uncertain and require more study," he said.

Same Risk for Unilateral and Bilateral Oophorectomy

Data for the 2 studies was derived from the Rochester Epidemiology Project, 1 of the largest long-term integrated databases of patient records in the world. All women who underwent bilateral or unilateral oophorectomy in Olmsted County, Minnesota, between 1950 and 1987 were identified.

Women who had undergone oophorectomy for ovarian cancer or as treatment for other estrogen-related malignancy were excluded.

The first study looked at the association between oophorectomy and the subsequent risk for cognitive impairment and dementia. It included 1489 subjects who had undergone oophorectomy, either bilateral (676) or unilateral (813), and 1472 age-matched women from the same population who had not had their ovaries removed.

Surprisingly, said Dr. Rocca, the risk for dementia and parkinsonism was similar irrespective of whether a woman had a bilateral or unilateral procedure. "This wasquite a distressing finding. Until relatively recently, it was thought that removing just 1 ovary or the uterus alone would leave adequate amounts of estrogen. However, our research suggests removing 1 ovary may have adverse consequences," he said.

He pointed out there is a growing body of recent research suggesting that women who undergo unilateral oophorectomy or removal of the uterus experience premature failure of the remaining ovary approximately 3 to 4 years before the approximate age of menopause.

Adjusted dementia risk associated with bilateral oophorectomy

Age at Surgery (y)
Hazard Ratio
95% CI
< 43
0.97– 3.14
43 – 48
1.06 – 2.66
> 48
0.74 – 1.61
Adjusted dementia risk associated with unilateral oophorectomy

Age at Surgery (y)
Hazard Ratio
95% CI
< 34
2.52 – 8.43
< 0.0001
34 – 41
0.67 – 2.26
> 41
1.05 – 2.13
Similarly, the second study, which included 2327 patients who had surgical removal of their ovaries (1252 unilateral and 1075 bilateral, respectively) and 2368 age-matched women, showed a comparable magnitude of risk associated with oophorectomy and parkinsonism.

Adjusted parkinsonism risk associated with oophorectomy

Age at Surgery (y)
Hazard Ratio
95% CI
< 38
1.28 – 6.35
38 – 45
0.63 – 3.01
> 45
0.92 – 3.03
"I hope these 2 papers will prompt discussion between cliniciansand their patients who are facing elective oophorectomy before age 50 years and that in addition to the risks for cancer, cardiovascular disease, and osteoporosis, such discussions will also include neurological disease," he said.

The 2 studies accompany a previous study by Dr. Rocca and colleagues published in Lancet Oncology (Rocca WA et al. Lancet Oncol. 2006;7:821-828) reporting an increased risk for mortality associated with bilateral oophorectomy before age 45 years. In addition, a fourth paper looking at psychiatric outcomes after oophorectomy will be published in the near future.

Currently, Dr. Rocca is seeking funding to replicate the findings of the dementia study in a new group of women using more sophisticated neuropsychological instruments and methods.

Neurology. Published online August 29, 2007.


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