Women are at increased risk for depressive symptoms during the menopause transition.  It has long been suspected that falling estrogen levels play a role in triggering the onset of depression; however, if all women experience declining levels of estrogen and progesterone during this transition, why is it that only some women suffer from depression in this setting?

A recent study has looked at how levels of estrogen and progesterone affect risk for depressive symptoms.  A total of 50 unmedicated perimenopausal women between the ages of 35 and 56 years (mean age, 48.4 ± 3.9 years) with mild-to-moderate depressive symptoms were recruited from Massachusetts General Hospital and Brigham and Women’s Hospital. Depressive symptoms, estradiol and progesterone serum levels, and vasomotor symptom (VMS) frequency were assessed each week for a total of 8 weeks.

In this group of women, 90% had varying estradiol levels and 90% reported VMS.  About half of the participants (51.1%) had levels of progesterone consistent with ovulation.  Higher levels of depressive symptoms were observed in women with greater variability in estradiol levels and lower progesterone levels (consistent with no ovulation).  VMS frequency was not associated with higher levels of depressive symptoms.  

Although previous studies have observed an association between more severe VMS and increased risk for depression, this study demonstrated that increasing dysregulation of ovarian hormones, but not VMS, was associated with more depressive symptom burden during the menopausal transition. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition and fluctuations in the levels of both estradiol and progesterone.


Ruta Nonacs, MD PhD


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. 2020 Mar 1; 105(3):e642-50. 

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