Women who begin taking oral or transdermal estrogen or estrogen/progestin for menopause between the ages of 45 and 50 appear to be at greater risk of developing depression, suggests a report that was published today in JAMA Network Open. The study of more than 825,000 women in Denmark found that the risk was highest during the first years after starting hormone therapy.
“Our findings suggest that around menopause, women may be more sensitive to the influence of [hormone therapy] on mood than at later ages,” wrote Marie K. Wium-Andersen, M.D., Ph.D., D.M.Sc., of Bispebjerg and Frederiksberg Hospitals in Denmark.
The study included 825,238 women in Denmark who turned 45 years between 1995 and the end of 2017. Women with a prior oophorectomy, breast cancer, and cancer in reproductive organs were excluded from the trial, as were the women who received hormone therapy before age 45. The researchers used the Danish National Prescription Registry to examine participants’ use of hormone therapy between 1995 and 2017 and the Danish Psychiatric Central Research Register and the Danish National Patient Registry to examine participants’ depression diagnoses from 1995 through 2018.
During the follow-up of about 11 years, 189,821 women (23.0%) initiated systemically (oral or transdermal) or locally administered (intravaginal or intrauterine) hormone therapy and 13,069 (1.6%) were diagnosed with depression.
Compared with women who did not use hormone therapy, those who did experienced a higher risk of being diagnosed with depression. For systemically administered hormone therapy, there was a higher risk of depression among younger women (hazard ratio [HR] for 48 to 50 years of age, 1.50) and a lower risk of depression with greater age (HR for 51 to 53 years of age, 1.13). Locally administered hormone therapy was associated with lower risk of depression when initiated when the women were older than 54 years (HR, 0.80) and was not associated with depression risk in women younger than 54 years (HR, 0.98).
“These findings suggest that women undergoing menopause who initiate systemically administered [hormone therapy] should be aware of depression as a potential adverse effect, and locally administered [hormone therapy] should be recommended when needed,” Wium-Andersen and colleagues wrote.
For related information, see the Psychiatric News article “Older Age at Menopause May Reduce Risk of Depression.”
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