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Peter Schmidt and his team have published some much needed research comparing the effects of the withdrawal of estrogen from women who have perimenopausal depression (PMD) with those who have continued the therapy [1]. After 3 weeks of open-label administration of transdermal estradiol (100 µg/day), participants were randomized to a parallel design to receive either estradiol (100 µg/day; 27 participants) or matched placebo skin patches (29 participants) for 3 additional weeks under double-blind conditions. The women completed the Center for Epidemiologic Studies-Depression Scale, the 17-item Hamilton Depression Rating Scale (completed by raters blinded to diagnosis and randomization status), and self-administered visual analog symptom ratings, and blood hormone levels were obtained at weekly clinic visits. The results showed that none of the 29 patients who received estradiol reported depressive symptoms but those who crossed over from estradiol to placebo experienced a significant increase in depressive symptoms. The conclusion was that, in women with a past history of PMD who had previous responded to hormone therapy, the recurrence of depressive symptoms during blinded hormone withdrawal suggests that changes in estradiol can trigger an abnormal behavioral state in these susceptible women. Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy and psychiatrists should be aware that there is more appropriate treatment than antidepressants and mood stabilizing drugs.


  • John Studd
    London PMS and Menopause Centre, London, UK


  1. 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 May 27. Epub ahead of print
  2. Studd J, Nappi RE. Reproductive depression. Gynecol Endocrinol 2012;28(Suppl 1):42-5
  3. Studd JW. A guide to the treatment of depression in women by estrogens. Climacteric 2011;14:637-42
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