Depression in women with spontaneous 46, XX primary ovarian insufficiency

Abstract

Context: A high prevalence of depressive symptoms is observed in women with primary ovarian insufficiency (POI) compared with women in whom the menopause is normally timed. Indeed, studies suggest that depression and/or its pharmacological treatment contribute to the onset of POI.

Objectives: We characterize the prevalence of psychiatric disorders and the timing of onset of clinically significant depression relative to both the diagnosis of POI and the onset of menstrual irregularity in women with POI.

Design and setting: We conducted a cross-sectional clinic-based study at the National Institutes of Health Clinical Research Center.

Patients: A total of 174 women with spontaneous 46, XX POI and 100 women with Turner syndrome participated in the study.

Main outcome measures: The structured clinical interview for DSM-IV was performed.

Results: Lifetime histories of depression in POI exceeded rates of depression reported in women with Turner syndrome and community-based samples of women (P < 0.001). The onset of depression frequently preceded the diagnosis of POI but occurred after the onset of menstrual irregularity. Analyses standardizing the periods of risk for depression showed that similar numbers of depressions occurred before and after these events.

Conclusions: POI is associated with an increased lifetime risk for major depression. Attention to the presence of depression in POI should become an important part of the care for these women. The onset of depression frequently occurs after signs of altered ovarian function but before the diagnosis of POI. Thus, in some women the association between POI and depression suggests an overlapping pathophysiology rather than a causal relationship.

Fig. 1.

Dates of onset of depression, POI, and MCI were estimated to the closest month and year. In women in whom the month could not be identified, we standardized the report to January of that year for all self-reported events. A, Episodes of major depression (solid histograms) and minor depression (hatched histograms) before and after the diagnosis of POI. B, Episodes of major depression (solid histogram) and minor depression (hatched histograms) before and after the reported onset of MCI. The x-axis represents the 2-yr intervals before or after the diagnosis of POI (A) or MCI (B). The y-axis represents the first episode of major depression in each woman or, in those women who reported no episodes of major depression, the y-axis represents the first episode of minor depression. In the majority of women, whereas the onset of depression preceded the diagnosis of POI (A), depression occurred most commonly after the onset of MCI (B), a proxy for the early stages of ovarian insufficiency in these women. Of the 95 women who experienced at least one major depression, a greater number (n = 65; 68.4%) reported the onset of depression before the diagnosis of POI than after the diagnosis of POI (n = 30; 31.6%). Similarly, in those 22 women with at least a single episode of minor depression, 13 women (59.1%) reported the onset of depression before the diagnosis of POI. When the analyses were adjusted for differing years of exposure to the risk of depression before and after the diagnosis of POI, there were comparable numbers of depressive episodes occurring before and after the diagnosis of POI (Table 4). A greater number of women (n = 67; 73.6%) also reported the onset of depression after the onset of MCI (B). Sixteen of the 22 women with minor depression (72.7%) reported the onset of depression after the onset of MCI. Analyses adjusting for the years of exposure to risk demonstrated comparable numbers of women who developed depression after and before the onset of MCI (Table 4). Of the 65 women who had a major depression before the POI diagnosis, the length of time between the major depressive episode and the diagnosis of POI was 5.4 ± 5.5 yr. In the 13 women in whom minor depression occurred before the diagnosis of POI, the average length of time between minor depression and POI diagnosis was 5.4 ± 4.8 yr. For women whose depression occurred after the diagnosis of POI, the average duration between the POI diagnosis and the onset of major depression was 3.7 ± 4.3 yr, and for those with minor depression, the average duration was 2.3 ± 1.7 yr. In the women with major depression occurring after MCI (n = 67), there was an average duration between the onset of MCI and depression of 5.0 ± 4.9 yr. In those 24 women whose depression preceded MCI, there was an average of 6.1 ± 4.9 yr between the onset of depression and MCI. Observations were similar in those women with minor depression. Minor depression occurred on average 4.3 ± 3.6 yr after MCI, and in those minor depressions occurring before MCI, a difference of 5.3 ± 4.2 yr separated the two events.