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Depression and Perimenopause - Janet Settle, MD
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Depression and Perimenopause

Depression and Perimenopause

What Is the Relationship Between Perimenopause and Depression?

Janet Settle MD reporting on four recent journal articles on depressive symptoms during the menopausal transition.

Depression during the menopausal transition is a hot (flash) topic! Google scholar lists 8730 results for “depression AND menopause” in 2015-16 alone. The findings of past studies have been mixed, but two new studies support the finding that depressive symptoms are more common during the menopausal transition. The definition of menopause is one year without a period. The average age of menopause is 51. The ‘menopause transition,’ during which periods are irregular but not absent, lasts an average of 4 years.

”Between 15% and 50% of women experience depressive symptoms during the menopausal transition; in 15% to 30% of perimenopausal women, they are severe enough to be regarded as a depressive disorder (Toffol, 2015).”

In a meta-analysis of 11 studies, authors conclude that, “Perimenopause is a phase in which women are particularly vulnerable to develop depressive symptoms” (OR 2.0 compared with pre menopause) “and have higher symptom severity compared to premenopause.The odds of depressive symptoms were higher but the odds of a major depressive episode were not (deKruif, 2016).

Why haven’t studies found a more robust correlation between menopausal symptoms and depression? One possibility is that a subset of women are particularly sensitive to mental health symptoms during hormonal transitions including PMS, postpartum depression and menopause. Population studies of mood disorders in perimenopausal women may not capture the increased risk for depression in this sensitive group. Two recent studies support this idea.

Schmidt et al (2015): Compared with women without history of depression, euthymic postmenopausal women with a past history of hormone responsive perimenopausal depression were found to develop new depressive symptoms after a 3-week course of topical estradiol treatment was discontinued. Neither group had depressive symptoms during the estradiol treatment. The control group did not have depressive symptoms after estradiol was withdrawn. The history of depression group did not have symptoms before or during the estradiol treatment but had new onset symptoms only when the estradiol was discontinued.

The authors conclude that “the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women.

Gordon et al (2016): In euthymic women ages 45-60, 61% of women reported 2 or more very stressful life events. In that group, “greater estradiol (blood level) variability over 14 months predicted greater depressive symptoms at month 14.”

The authors conclude that estradiol variability may enhance emotional sensitivity to psychosocial stress.They go on to say that, Combined with very stressful life events proximate to the menopausal transition, this increased sensitivity may contribute to the development of depressed mood.

There is support in the literature for the safe use of bioidentical hormone replacement therapy (BHRT) when initiated at or near the time of menopause. The standard of care includes weighing the risks and benefits of BHRT for each woman. In some vulnerable women, the psychiatric risks of no hormone replacement may outweigh the risks of BHRT. Women vulnerable to the mood effects of changing hormone levels are likely over-represented in a psychiatric practice. In my practice, BHRT improves psychiatric outcomes. Some cases of treatment resistantdepression respond to conventional or integrative treatment approaches once hormone deficiencies have been addressed.

de Kruif et al. Depression during the perimenopause: A meta-analysis. Journal of Affective Disorders. Dec 2016;206.

Gordon et al. Estradiol variability, stressful life events, and the emergence of depressive symptomatology during the menopausal transition. Menopause. 2016; 23(3), 257-266.

Schmidt et al. Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression: A Randomized Clinical Trial. JAMA psychiatry. 2015; 72(7), 714-726.

Toffol et al. Hormone therapy and mood in perimenopausal and postmenopausal women: a narrative review. Menopause. 2015;22(5).

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