After Oophorectomy, Cognitive Impairment Risks Rise

ROCHESTER, Minn., Aug. 29 -- There is evidence of a neuroprotective effect of estrogen from two studies that found women were at an increased risk for dementia and parkinsonism after their ovaries were removed before natural menopause.
Unilateral or bilateral oophorectomy was associated with a 46% increase in risk of cognitive impairment or dementia, and a 68% increase in risk for parkinsonism, reported Walter A. Rocca, M.D., M.P.H., of the Mayo Clinic, and colleagues.
The effect of estrogen deprivation on neural function appeared to be age dependent, with risk increasing significantly for women who were younger at the time of oophorectomy, the authors reported in the studies, both published online in Neurology.
The findings support laboratory studies that have pointed to a neuroprotective effect of estrogen, and indicate that physicians and patients should carefully consider the consequences of pre-menopausal hormonal deprivation.
"Although almost 60% of women received some estrogen treatment after both of their ovaries were removed, only 20% of them received estrogen treatment until at least age 50," the median age when women reach menopause, Dr. Rocca said.
The investigators conducted two retrospective studies of women who took part in the Mayo Clinic Cohort Study of Oophorectomy and Aging, which included 1,433 women living in Olmsted County, Minn., who underwent unilateral oopherectomies and 1,824 who underwent bilateral ovary excision for non-cancer indications from 1950 through 1987. The patients were compared with age-matched referents from the same population who had their ovaries intact.
In the study of potential associations between oophorectomy and cognitive function, the authors looked at 813 women with unilateral oophorectomy, 676 women with bilateral excision, and 1,472 controls. The women were followed through death or study end with either direct or proxy interviews.
They found in an analysis adjusted for education, type of interview, and history of depression that women who underwent either unilateral or bilateral excision had a hazard ratio for cognitive impairment or dementia of 1.46 (95% confidence interval, 1.13 to 1.90).
When they stratified patients by age at the time of oophorectomy, they saw a trend of increasing risk with younger age (test for linear trend in the adjusted log hazard ratio, P<0.001). This effect was seen regardless of the indication for surgery.
Many of the women in the dementia study were also included in the cohort of the study looking for possible associations between oophorectomy and parkinsonism.
In that study, the authors looked at 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 controls. As in the dementia study, the women were followed through death or end of study with direct or proxy interviews, plus the addition of neurologic examinations, medical records in a records-linkage system, and death certificates.
The researchers found that, compared with women in the referent sample, women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism, with a hazard ratio of 1.68 (95% CI 1.06 to 2.67; P=0.03).
Here too, the risk increased with younger age at oophorectomy (test for linear trend, P=0.01), and again the findings were similar regardless of the indication for the procedure, as well as for unilateral or bilateral oophorectomy considered separately.
"The observed trends of increased risk of parkinsonism with younger age at oophorectomy suggest that the neuroprotective effect of estrogen on the nigrostriatal pathway may be age-dependent and may have a critical age window," the authors wrote. "A similar concept of a critical age window for neuroprotection has been proposed for cognitive decline and dementia."
The authors proposed three possible mechanisms for the effects they saw: loss of estrogen neuroprotection, loss of neuroprotecion from progesterone and/or testosterone, and genetic predisposition to conditions requiring oophorectomy and to cognitive impairment, dementia or parkinsonism.
They acknowledged that the studies were limited by potential inaccuracies in the diagnoses of the neural disorders, cognitive impairment, dementia, and parkinsonism, reliance on telephone or proxy interviews rather than face-to-face interviews, and, in the case of parkinsonism, by potentially confounding socioeconomic factors.
Both studies were supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported no conflicts of interest. Primary source: NeurologySource reference: Rocca WA et al. "Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause." Neurology 2007; 69: 1074-1083.