Publication Date


UMMS Affiliation

Graduate School of Nursing

Document Type

Article Postprint


Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists | Polycyclic Compounds | Psychiatry and Psychology | Psychological Phenomena and Processes | Reproductive and Urinary Physiology | Women's Health


OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology.

DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models.

SETTING: Academic medical center.

PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scale [MADRS] score 15.5 +/- 5.3).

RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (beta= 0.11, 95% confidence interval [95%CI] [0.04 to 0.18, p=0.001]; beta= -2.62 [95%CI -4.52 to -0.71, p=0.007], respectively), after accounting for higher BMI, lifetime history of depression, and stressful life events.

CONCLUSIONS: Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.


depression, estradiol, mood, ovulation, perimenopause, progesterone

Rights and Permissions

© Endocrine Society 2019. Accepted manuscript posted after 12 months as allowed by publisher's self-archiving policy at

DOI of Published Version



Joffe H, de Wit A, Coborn J, Crawford S, Freeman M, Wiley A, Athappilly G, Kim S, Sullivan KA, Cohen LS, Hall JE. Impact of estradiol variability and progesterone on mood in perimenopausal women with depressive symptoms. J Clin Endocrinol Metab. 2019 Nov 6;dgz181. doi: 10.1210/clinem/dgz181. [Epub ahead of print]. PMID: 31693131. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of clinical endocrinology and metabolism

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PubMed ID