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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).
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.
The study is a “commendable effort” to examine the role of reproductive hormones in postmenopausal depression, but several important caveats should temper enthusiasm for its conclusions, Dr. Hadine Joffe and Joyce T. Bromberger, Ph.D., wrote in an accompanying editorial.
In most of the studies, women were aged 55-60 years – considerably beyond the average menopausal age of 52. Additionally, most were at least 5 years past their menopause, reflecting a group that might have passed the period of highest risk for hormone-mediated depression.
“This meta-analysis does not address depression associated with the gonadal steroid fluctuations of the perimenopause or recent estradiol withdrawal of the immediate postmenopause,” the colleagues wrote. “Rather, the analysis applies to depression in older women whose brains have not recently been exposed to estradiol or other reproductive hormones and for whom hormonal risk factors have previously been considered less relevant.”
However, the study is one of the few to investigate the psychotropic effects of estrogen on aging women. “In contrast to the acute effects of reproductive hormones on mood in cycling women, the article highlights a potential neuroprotective effect of gonadal steroids on mood that is delayed and extends into the stable hypoestrogenic and hypoprogestinemic environment of the postmenopause.”
Its conclusions are strengthened by studies of nonpsychiatric diseases associated with earlier menopause, including cardiovascular disease, cognitive decline, and dementia. Nevertheless, it’s too early to recommend prophylactic hormone therapy, the authors concluded.
“Given the small effect size and limitations of the studies used in this analysis, 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.”
Dr. Joffe is director of the Women’s Hormone and Aging Research Program at Brigham and Women’s Hospital, Boston. Dr. Bromberger is a professor of epidemiology and psychiatry at the University of Pittsburgh.
The study is a “commendable effort” to examine the role of reproductive hormones in postmenopausal depression, but several important caveats should temper enthusiasm for its conclusions, Dr. Hadine Joffe and Joyce T. Bromberger, Ph.D., wrote in an accompanying editorial.
In most of the studies, women were aged 55-60 years – considerably beyond the average menopausal age of 52. Additionally, most were at least 5 years past their menopause, reflecting a group that might have passed the period of highest risk for hormone-mediated depression.
“This meta-analysis does not address depression associated with the gonadal steroid fluctuations of the perimenopause or recent estradiol withdrawal of the immediate postmenopause,” the colleagues wrote. “Rather, the analysis applies to depression in older women whose brains have not recently been exposed to estradiol or other reproductive hormones and for whom hormonal risk factors have previously been considered less relevant.”
However, the study is one of the few to investigate the psychotropic effects of estrogen on aging women. “In contrast to the acute effects of reproductive hormones on mood in cycling women, the article highlights a potential neuroprotective effect of gonadal steroids on mood that is delayed and extends into the stable hypoestrogenic and hypoprogestinemic environment of the postmenopause.”
Its conclusions are strengthened by studies of nonpsychiatric diseases associated with earlier menopause, including cardiovascular disease, cognitive decline, and dementia. Nevertheless, it’s too early to recommend prophylactic hormone therapy, the authors concluded.
“Given the small effect size and limitations of the studies used in this analysis, 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.”
Dr. Joffe is director of the Women’s Hormone and Aging Research Program at Brigham and Women’s Hospital, Boston. Dr. Bromberger is a professor of epidemiology and psychiatry at the University of Pittsburgh.
The study is a “commendable effort” to examine the role of reproductive hormones in postmenopausal depression, but several important caveats should temper enthusiasm for its conclusions, Dr. Hadine Joffe and Joyce T. Bromberger, Ph.D., wrote in an accompanying editorial.
In most of the studies, women were aged 55-60 years – considerably beyond the average menopausal age of 52. Additionally, most were at least 5 years past their menopause, reflecting a group that might have passed the period of highest risk for hormone-mediated depression.
“This meta-analysis does not address depression associated with the gonadal steroid fluctuations of the perimenopause or recent estradiol withdrawal of the immediate postmenopause,” the colleagues wrote. “Rather, the analysis applies to depression in older women whose brains have not recently been exposed to estradiol or other reproductive hormones and for whom hormonal risk factors have previously been considered less relevant.”
However, the study is one of the few to investigate the psychotropic effects of estrogen on aging women. “In contrast to the acute effects of reproductive hormones on mood in cycling women, the article highlights a potential neuroprotective effect of gonadal steroids on mood that is delayed and extends into the stable hypoestrogenic and hypoprogestinemic environment of the postmenopause.”
Its conclusions are strengthened by studies of nonpsychiatric diseases associated with earlier menopause, including cardiovascular disease, cognitive decline, and dementia. Nevertheless, it’s too early to recommend prophylactic hormone therapy, the authors concluded.
“Given the small effect size and limitations of the studies used in this analysis, 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.”
Dr. Joffe is director of the Women’s Hormone and Aging Research Program at Brigham and Women’s Hospital, Boston. Dr. Bromberger is a professor of epidemiology and psychiatry at the University of Pittsburgh.
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).
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.
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).
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.
FROM JAMA PSYCHIATRY
Key clinical point: Later menopause, with its longer estrogen exposure, appears tied to a lower risk of postmenopausal depression.
Major finding: The risk of depression decreased by 2% for each 2 premenopausal years after age 40.
Data source: The meta-analysis comprised 14 studies with more than 67,700 women.
Disclosures: Neither Dr. Georgakis nor any of the coauthors declared any financial conflicts.
