Depression increases in frequency in women undergoing the menopause. This has been suggested to reflect the perimenopausal decline in estradiol levels; consequently, estradiol therapy may help reduce perimenopausal depression (PMD) risk.
This hypothesis has now been tested for the first time, with positive results. Two groups of asymptomatic postmenopausal women — 26 with past PMD responsive to hormone therapy and 30 with no history of depression — received transdermal estradiol for three weeks before being randomised to receive estradiol or placebo skin patches for three weeks.
None of the women reported depressive symptoms during estradiol use. However, depression-prone women who were switched from estradiol to placebo patches experienced a significant increase in depressive symptoms. “Normal changes in ovarian estradiol secretion can trigger an abnormal behavioural state in susceptible women,” the researchers conclude in JAMA Psychiatry
(online, 27 May 2015).
 Schmidt PJ, Ben Dor R, Martinez PE et al. Effects of estradiol withdrawal on mood in women with past perimenopausal depression: a randomized clinical trial. JAMA Psychiatry 2015. doi:10.1001/jamapsychiatry.2015.0111.