The longer a woman’s reproductive years last, the less she may be prone to postmenopausal depression, a large meta-analysis has determined.
The risk of depression declined by 2% for every 2 premenopausal years after age 40. Women who entered menopause after age 40 experienced a 50% decrease in the risk of depression, compared with women who experienced premature menopause, Dr. Marios K. Georgakis and colleagues reported Jan. 6 in JAMA Psychiatry (2016. doi:10.1001/jamapsychiatry.2015.2653).
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The findings suggest that longer exposure to endogenous estrogens mediates the pathophysiology of late-life depression, wrote Dr. Georgakis of the National and Kapodistrian University of Athens and coauthors.
“If confirmed in prospective and culturally diverse studies … these findings could have a significant clinical effect by allowing for the identification of a group of women at higher risk for depression who may benefit from psychiatric monitoring or estrogen-based therapies.”
The meta-analysis comprised 14 studies that included 67,714 women. They controlled for numerous factors, including age, body mass index, obesity, smoking, and hormone therapy. However, only two controlled for past depression – one of the biggest risk factors for recurring depression.
In addition to the 2% decline per 2 premenopausal years after 40, a subanalysis of three studies examining severe depression found a 5% decreased risk for the same time measure. Another analysis of women with premature menopause found a doubling in the risk of depression for those who experienced menopause before age 40.
Estrogen is known to have neuroprotective and antidepressive properties, and the brain is richly endowed with estrogen receptors, the authors said. The exact pathway of protection against depression, however, remains unknown. Potentiation of neurotransmitters and moderation of atherosclerosis might play protective roles.
“Given the results of our study, it remains to be investigated whether women with menopause at younger ages could benefit by preventive use of hormone therapy against late-life depression, provided that adverse effects associated with long-term use are considered,” the authors said. “In this context, the development of estrogen receptor subtype–specific ligands could decrease the proportion of estrogen therapy adverse effects.”
Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.