NASHVILLE, TENN. — Perimenopause does induce depression in a subgroup of women, as illustrated by results of several recent studies and by early findings from his own investigation, Dr. Peter J. Schmidt said at the annual meeting of the North American Menopause Society.
He and his colleagues conducted an observational study of 29 asymptomatic premenopausal women with regular menses and followed them with reproductive and behavioral measures for a mean of 5 years until they had gone through menopause.
Episodes of depression occurred sporadically, he reported, until the year before the last menstrual period, when the investigators observed four episodes of depression, followed by five episodes in the year after the last menstrual period. Overall, there were nine depressive episodes in eight women. Only two of the women had a prior history of depression, he noted.
“Overall, then, within the 24 months surrounding the last menstrual period, we identified approximately a 14-fold increased risk for an episode of depression to occur,” said Dr. Schmidt, chief of behavioral endocrinology at the National Institutes of Health, Bethesda, Md.
He noted that these happened late in the menopausal transition—a period marked by estrogen withdrawal and hypogonadism.
Despite assertions by some studies in the literature that the onset of menopause is not directly associated with mood disorders in women, considerable laboratory evidence bears out the relationship between estrogen and depression, Dr. Schmidt said.
Anxious phenotype has been implicated in studies of estrogen-receptor-knockout mice, and compounds that selectively modulate the estrogen receptor β have been identified as anxiolytic and reduce stress response to a novel environment.
Dr. Schmidt emphasized that depression has measurable physiologic consequences for women and noted as an example that one observational study from the Women's Health Initiative found that in women who had no history of cardiovascular problems, depressive symptoms were linked to an increased risk of cardiac death over 5 years' follow-up (Arch. Intern. Med. 2004;164:289–98).
Other negative outcomes linked to depression are stroke, metabolic syndrome, and dementia. He cited recent community-based epidemiologic studies that followed women with no prior history of depression and found that onset of menopause was associated with a 2–2.5-fold risk of depression.
He noted that several studies have found that depression frequently precedes a comorbid condition by several years, “suggesting in fact that depression is causing the medical condition or that the two conditions share a similar pathophysiology.”