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Dept of Medicine, Division of Preventive and Behavioral Medicine; Graduate School of Nursing

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Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Psychiatry and Psychology | Reproductive and Urinary Physiology | Women's Health


OBJECTIVE: Irritability 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.

METHODS: Among 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.

RESULTS: Most 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 beta 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.

CONCLUSIONS: Irritability 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.


Depression, Irritability, Perimenopause, Predictors, Reproductive hormones

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© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (

DOI of Published Version



de Wit AE, Giltay EJ, de Boer MK, Nathan M, Wiley A, Crawford S, Joffe H. Predictors of irritability symptoms in mildly depressed perimenopausal women. Psychoneuroendocrinology. 2021 Jan 7;126:105128. doi: 10.1016/j.psyneuen.2021.105128. Epub ahead of print. PMID: 33493755. Link to article on publisher's site

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.