Menopause and anxiety: immediate and long-term effects.

B ased on data from the National Hospital Discharge Survey from the year 2000-2004, it is estimated that approximately 600,000 women in the United States undergo hysterectomies each year, at a rate of 5.1 per 1000 in 2004. The rate of bilateral oophorectomy among women with hysterectomy declined from 55.1% in 2000 to 49.5% in 2004 and varied by age such that hysterectomy accompanied bilateral oophorectomy in 37% of women aged 15 to 44 years compared with 78% of women aged 50 to 54 years. The immediate and long-term health consequences of early bilateral oophorectomy, particularly among young women, are a major public health concern. Studies by Walter Rocca and his colleagues from the Mayo Clinic Cohort Study of Oophorectomy and Aging have greatly informed our understanding of the health risks associated with early oophorectomy. The study involves a population-based cohort of women residing in Olmsted County, MN, who underwent oophorectomy before the onset of menopause for a noncancer indication during the 38-year period from 1950 to 1987. Median follow-up periods are 25 years or more, depending on the publication and cohort. In a major finding from this cohort study, overall mortality was not significantly increased in women who underwent oophorectomy, but women who had the surgery before the age of 45 years had a higher mortality risk compared with referent women (adjusted hazard ratio (HR), 1.67; 95% CI, 1.16-2.40). This increased mortality risk was primarily observed among women who had not received estrogen up to the age of 45 years. No increased mortality was evident in women who underwent unilateral oophorectomy. Another notable publication from this cohort revealed that women who underwent either unilateral or bilateral oophorectomy had a increased risk of cognitive impairment or dementia compared with women with natural menopause (adjusted HR, 1.46; 95% CI, 1.13-1.90), and estrogen therapy protected against that risk. In a third study, the risk of Parkinson disease was higher in women who underwent either unilateral or bilateral oophorectomy (adjusted HR, 1.68; 95% CI, 1.06-2.67). In both studies, a younger age at menopause was associated with increased risk of neurological impairment (ie, the linear trend was significant). These findings underscore the importance of considering the long-term health consequences of oophorectomy, particularly early oophorectomy. In the article entitled BLong-term Risk of Anxiety and Depressive Symptoms Following Early Bilateral Oophorectomy[ in this issue of Menopause, Rocca and his colleagues provide important new information on the longterm risk of depressive and anxiety symptoms after bilateral oophorectomy. He and his research team examined these symptoms in 666 women who had undergone bilateral oophorectomy and 673 referent women. Women with a history of self-reported anxiety or depressive disorders and women who underwent unilateral oophorectomy were excluded from the analysis. The outcome measure was anxiety symptoms, defined as a self-reported history of anxiety disorders on a structured questionnaire developed for, and validated in, the study. Depressive symptoms were also measured by a structured questionnaire that targeted self-reported depressive disorders and was previously validated. These outcomes were documented by telephone interviews using a technique that showed good reliability with medical records and physician interviews. For a median follow-up period of 24 years, the risk of anxiety symptoms increased significantly in women who underwent bilateral oophorectomy compared with referent women (adjusted HR, 2.29; 95% CI, 1.33-3.95). The increased risk of anxiety symptoms was particularly evident among women who underwent surgery before the age of 48 years (adjusted HR, 2.66; 95% CI, 1.39-5.09). Bilateral oophorectomy was also a risk factor for depression diagnosed by a physician (adjusted HR, 1.54; 95% CI, 1.04-2.26). Estrogen use did not modify the risk of either of these symptoms. It is helpful to put these results in the context of what is known about sex differences in anxiety. The prevalence of anxiety disorders in the general US population is about 26.6%. The prevalence is higher in women compared with men and increases significantly in women, but not in men, at midlife (after age 45 years). Anxiety traits in nonclinical samples are also more common in women than in men. The findings of Rocca and colleagues might shed light on bilateral oophorectomy as one of the factors that increases the risk of anxiety disorders and anxiety symptoms in women. One important consideration in understanding the relationship between oophorectomy and anxiety is the finding that women who undergo prophylactic oophorectomy at elective hysterectomy have been shown to have increased anxiety before surgery. The baseline data in the study of Rocca et al seem to support those findings. In that cohort, 50% of surgeries were prophylactic, and 94% were in conjunction with hysterectomy. Among women who underwent bilateral