Increased risk of parkinsonism in women who underwent oophorectomy before menopause

OBJECTIVE: There is increasing laboratory evidence for a neuroprotective effect of estrogen on the nigrostriatal pathway; however, the epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent parkinsonism. METHODS: We included all women who underwent either unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987 while residing in Olmsted County, MN. Each member of the oophorectomy cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed through death or end of study using a combination of direct or proxy interviews, neurologic examinations, medical records in a records-linkage system, and death certificates. RESULTS: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with referent women (HR 1.68; 95% CI 1.06 to 2.67; p = 0.03), and the risk increased with younger age at oophorectomy (test for linear trend; p = 0.01). The findings were similar regardless of the indication for the oophorectomy, and for unilateral or bilateral oophorectomy considered separately. The findings were also consistent for Parkinson disease alone, but did not reach significance. CONCLUSIONS: Both unilateral and bilateral oophorectomy performed prior to menopause may be associated with an increased risk of parkinsonism and the effect may be age-dependent. However, our findings await independent replication.