Abstract
ObjectiveIrritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood. MethodsAmong 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0–23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models. ResultsMost women (82.0%) reported having moderate to severe irritability at least once. However, the severity of irritability was highly variable from week-to-week (between-subject mean coefficient of variation [CV] 72.9% and within-subject mean CV 63.7%). In multivariate analyses, less variable serum estradiol levels (standardized β within-person CV −0.23 95%CI [−0.32, −0.14], p < 0.001), greater depression severity (0.45 [0.35, 0.56], p < 0.001), younger age (−0.23, [−0.28, −0.09], p < 0.001), and more frequent vasomotor symptoms (0.14 [0.05, 0.23], p = 0.002) were associated with more irritability. Depression severity explained the largest portion of the variance in irritability, but still not more than 20.3%. Neither crude values, weekly change in, or variability of progesterone or FSH levels were associated with irritability. ConclusionsIrritability was highly prevalent among mildly depressed perimenopausal women. In contrast to depressive symptoms, decreased rather than increased variability in estradiol levels was associated with more irritability. This highlights that irritable mood can be disentangled from depressive symptoms in perimenopausal women and might be linked with different estradiol dynamics.
Highlights
Irritability, defined as a low threshold for experiencing frustration or anger, is prevalent during the perimenopause (Freeman et al, 2008; Bromberger et al, 2003; Mauas et al, 2014)
Subjects were included based on mild-to-moderate depressive symptoms defined as a score 10–25 on the Montgomery-Åsberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979), and/or moderate irritability, defined as a score > 7.7 on the Hostility scale of the Symptom Questionnaire (SQ) (Kellner, 1987) to ensure that the sample represented the rich variety of mood symptoms that manifest during the perimenopause
Women who had less variable serum estradiol levels, more frequent vasomotor symptoms (VMS), or who were younger, reported more irritability, associations that were independent of depression severity
Summary
Irritability, defined as a low threshold for experiencing frustration or anger, is prevalent during the perimenopause (Freeman et al, 2008; Bromberger et al, 2003; Mauas et al, 2014). Three large studies have examined risk factors for irritability, defined using a single question, in midlife women transitioning from pre- to post-menopause (Freeman et al, 2008; Bromberger et al, 2003, 2001). This study showed that mean levels of estradiol or follicle stimulation hormone (FSH) obtained every nine to twelve months over nine years were not associated with concurrent moderate to severe irritability (Freeman et al, 2008). We conducted an eight-week observational study in perimeno pausal women with untreated depressive symptoms, whereby weekly assessments of reproductive hormones and other predictors were ob tained concurrent with assessment of irritability and depressive symp toms using well validated questionnaires
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