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To investigate the mortality associated with cardiovascular diseases and the effect of estrogen treatment in women who underwent unilateral or bilateral oophorectomy before menopause.We conducted a cohort study with long-term follow-up of women in Olmsted County, MN, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied the mortality associated with cardiovascular disease in a total of 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women.Women who underwent unilateral oophorectomy experienced a reduced mortality associated with cardiovascular disease compared with referent women (hazard ratio [HR], 0.82; 95% CI, 0.67-0.99; P = 0.04). In contrast, women who underwent bilateral oophorectomy before age 45 years experienced an increased mortality associated with cardiovascular disease compared with referent women (HR, 1.44; 95% CI, 1.01-2.05; P = 0.04). Within this age stratum, the HR for mortality was significantly increased in women who were not treated with estrogen through age 45 years or longer (HR, 1.84; 95% CI, 1.27-2.68; P = 0.001) but not in women treated with estrogen (HR, 0.65; 95% CI, 0.30-1.41; P = 0.28; test of interaction, P = 0.01). Mortality was further increased after deaths associated with cerebrovascular causes were excluded.Bilateral oophorectomy performed before age 45 years is associated with increased cardiovascular mortality, especially with cardiac mortality. However, estrogen treatment may reduce this risk.