Postpartum depression (PPD) is the most common unrecognized complication of childbirth and affects 1 out of 7 childbearing women. Although conventional pharmacologic and psychotherapeutic antidepressant treatments are effective for PPD, a natural alternative may be preferred by postpartum women, especially those who breastfeed their infants. The treatment of PPD with synthetic forms of naturally occurring estrogen is mechanistically appealing because PPD occurs in the context of estrogen withdrawal at parturition. Preliminary evidence suggests that PPD is a disorder of hormone-related mood dysregulation (similar to perimenopausal depression) that can be effectively treated with estrogen. This review provides the basic science and clinical background as well as safety considerations to support the application of transdermal estradiol as a treatment for PPD. We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial before routine clinical use as monotherapy. Additional data regarding maternal tolerability of cyclic progestins, long-term safety of estradiol treatment, estradiol passage into breast milk and infants, and interdisciplinary collaboration among psychiatrists and gynecologists is also needed before estradiol is used in women who decline or fail to respond to first-line antidepressant treatments, or as an augmentation of conventional antidepressant treatment.
*Department of Psychiatry
†Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
‡Department of Obstetrics and Gynecology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
§Obstetrics and Gynecology and Reproductive Sciences, Epidemiology, and Women's Studies, Women's Behavioral HealthCARE, Western Psychiatric Institute and Clinic
Financial Disclosures: Dr Wisner has received grant support from Pfizer and is currently on the speaker's bureau of Glaxo-Smith-Kline. Dr Berga has served intermittently in an advisory capacity to the following companies that manufacture menopause hormone replacement and contraceptive products: Bayer Schering Pharma, Upsher-Smith Laboratories Inc, Wyeth, Pfizer, and Novogyne Pharmaceuticals. She has received grant support from Pfizer and has lectured on menopause hormone therapy on behalf of Novogyne Pharmaceuticals and Upsher-Smith Laboratories, Inc. Dr Berga has also received grant support from Pfizer. Drs Wisner, Moses-Kolko, Sit, and Kalro are conducting a trial of transdermal estradiol for postpartum depression with the donation of placebo patches from Novogyne Pharmaceuticals, a joint venture between Novartis Pharmaceuticals Corporation and Noven Pharmaceuticals, Inc. Dr Moses-Kolko also receives NIMH and NARSAD Foundation support. Dr Wisner has also received grant support from: National Institute of Mental Health (SBIR #043), Stanley Medical Research Foundation, the State of Pennsylvania, and the Heinz Foundation. Dr Sit also received support through an International Society for Bipolar Disorders (ISBD) Fellowship Award.
Dr Moses-Kolko's contribution to this work was supported by National Institute of Mental Health K23 MH64561, R01 MH079164, and R01 MH057102 (K. Wisner, PI). Dr Berga's efforts related to this work were supported primarily by NIH R01 MH079164 (E. Moses-Kolko, PI). Dr Kalro's contributions were supported by National Institute of Mental Health R01 MH057102 (K. Wisner, PI). Dr Sit's contributions were supported by National Institute of Mental Health R01 MH60335 (K. Wisner, PI) and the Junior Faculty Scholars Program, and National Institute of Mental Health R25 MH060473 (P. Pilkonis, PI). Dr Wisner's effort was supported primarily by National Institute of Mental Health R01 MH057102.
Correspondence: Eydie L. Moses-Kolko, MD, Department of Psychiatry, Women's Behavioral HealthCARE, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA. E-mail: mosesEL@upmc.edu