Perimenopausal Mood Instability May Be Due to Dysregulation of Estradiol and Progesterone Levels

Posted on June 05, 2020

Read Story

Source: Medpage Today

Link between progesterone and depressive symptoms is new, and may have therapeutic implications

Women are particularly vulnerable to mood disturbances, ranging from subsyndromal depressive symptoms to major depression, during the menopausal transition period. While epidemiologic studies consistently demonstrate this, our understanding of the biological mechanisms for these prevalent symptoms remains limited.

An observational study by Joffe et al., published in the Journal of Clinical Endocrinology & Metabolism, has identified an association between mild to moderate depressive symptoms and changes in reproductive hormonal profile -- specifically, greater variability in estradiol levels and the absence of ovulatory progesterone levels in the perimenopausal period. This study evaluated weekly serum levels of estradiol and progesterone concurrently with severity of depressive symptoms in 50 women who were in early or late menopausal transition. This unique study design allowed the investigators to conclude that perimenopausal mood instability may be attributed to dysregulation of estradiol and progesterone levels.

Furthermore, the association found between progesterone levels and depressive symptoms is new and may have therapeutic implications for the use of allopregnanolone, a progesterone-derived neurosteroid recently approved for treatment of postpartum depression, in perimenopausal mood disturbances in the future.

Surprisingly, vasomotor symptoms were not found to be associated with depressive symptom severity, although this may have been masked due to high prevalence (90%) of these symptoms in the participants.

Overall, the findings of this study can help clinicians in counseling perimenopausal patients regarding the physiological explanations behind their fluctuating mood symptoms and may influence considerations for the addition of estrogen therapy to antidepressant therapy to treat perimenopausal mood symptoms. This study may also provide impetus for research into novel therapeutic targets for perimenopausal depression, such as progesterone-based agents.