Later Menopause Linked to Reduced Postmenopausal Depression Risk

Postmenopausal women have a lower risk of depression the later they experience menopause, found a meta-analysis published in JAMA Psychiatry.

The meta-analysis involved a total of 67 714 women from 14 studies, culled from more than 12 000 MEDLINE-indexed articles screened by a team led by Marios K. Georgakis, MD, of the School of Medicine at the National and Kapodistrian University of Athens in Greece. They included only cohort, case-control and cross-sectional studies that investigated depression in postmenopausal women based on age of menopause or duration of reproductive period.

For every two years older women were at menopause, they had 2% reduced odds of later depression based on 13 of the studies. This 2% reduction remained in an analysis of the three studies (involving 48 894 women) that controlled for past depression. Three studies explored risk of severe depression in a combined 52 736 women and found a 5% reduced risk of depression for every two additional years of a woman’s age at menopause.

Women who experienced menopause at age 40 or older were half as likely to experience depression compared to those with premature menopause, based on four of the studies involving 3033 women. Most of the studies involved women whose average age was 55 or older, and half included women averaging 60 years old or older.

“Results of this study provide a novel paradigm for understanding the potential impact of central nervous system exposure to female reproductive hormones and depression,” wrote Hadine Joffe, MD, of Harvard Medical School, and Joyce T. Bromberger, PhD, of the University of Pittsburgh in an accompanying editorial. “The implication is that prior and cumulative exposure to hormones has a sustained impact on the brain, increasing vulnerability to depression years after these exposures.”

They note that other conditions, such as cardiovascular disease, cognitive decline and dementia, have also been linked to an earlier age at menopause. Among the paper’s limitations are how few studies controlled for past depression, the small effect found, reliance on primarily cross-sectional studies and ones using self-reported scales to measure depression, inclusion of women currently or previously using hormone therapy, and retrospectively self-reported menopause and menarche.

“More direct evidence supporting a sustained and delayed neuroprotective effect of extended exposure to estradiol, cyclic progestins and their neurosteroid derivatives is required to support use of hormonal therapy as a therapeutic approach to protecting against postmenopausal depression,” Joffe and Bromberger wrote.


Georgakis MK, Thomopoulos TP, Diamantaras AA, et al. Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2016; doi: 10.1001/jamapsychiatry.2015.2653.