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Am Fam Physician. 2003;68(3):540-543

Depression may have a negative impact on the neuroendocrine system that controls ovarian function. This speculation arises because women with early-onset menarche are at an increased risk for depression later in life. A recent study found that women with depression had lower levels of estrogen and higher levels of luteinizing hormone (LH). Women in one study who had a history of depression requiring pharmacologic therapy were two to three times more likely to report menopause before 47 years of age than those who had no history of depression requiring treatment. Few studies have documented the impact that major depression has on the early transition to menopause. Harlow and colleagues studied whether depression could represent a risk factor for a precipitous decline in ovarian function and if depression is a marker for that same decline in ovarian function that precedes the cessation of menstruation by several years.

The participants were from a population-based, cross-sectional sample of women between 36 and 44 years of age from a metropolitan community. To qualify for enrollment, they had to have a history of depression that met the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for major depression. A matched control population who had no history of major depression was then selected from the sample. Patients were assessed for major depression and its severity if present and information concerning lifestyles, menstrual and reproductive history, past and current medical conditions, and the use of hormonal or nonhormonal medications at the start of the study and every six months for 36 months. Perimenopause was defined as a change of seven days or more in the menstrual cycle, a change in the menstrual flow amount or duration, or amenorrhea for at least three consecutive months. Hormonal assessment including LH, follicle-stimulating hormone (FSH), and estradiol was performed at day 2, 3, or 4 of the menstrual cycle every six months.

Women with a history of depression had a higher rate of perimenopause when compared with those who had no history of depression. Those with pronounced depressive symptoms had twice the risk of earlier perimenopausal transition. Participants who required antidepressant medication to treat their depression had almost three times the risk of an earlier perimenopausal transition than the women without a history of depression. With regard to hormonal evaluation, women with a history of lifetime depression had higher levels of serum LH and FSH and lower levels of estradiol at the start of the study and during the follow-up period. This was significant even after adjustments for covariants.

The authors conclude that a lifetime history of major depression may be associated with an early decline in ovarian function. This early transition to perimenopause may result in prolonged exposure to a hypoestrogenic state, which is associated with bone density loss, sexual dysfunction, a decline in cognitive function, and a potential increased risk for cardiovascular disease.

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