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Hormonal replacement therapy in postpartum affective disorders

Yokesh Balaraman, MBBS

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

Alan D. Schmetzer, MD

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

KEYWORDS: bipolar disorder, puerperal psychosis, estrogen



The risk of puerperal psychosis is estimated to be 1 in 1000 births, and the risk is increased in women with a history of bipolar disorder.1 Low estradiol levels in women experiencing puerperal psychosis have been found to correlate with high scores on the Brief Psychiatric Rating Scale and psychiatric symptoms have been reported to respond to estrogen therapy.2 Prophylactic estrogen treatment in women with a history of puerperal psychosis has been shown to reduce the incidence of puerperal psychosis.3 Huang et al4 reported therapeutic response to hormone replacement therapy with an estrogen-progesterone combination in a patient with treatment-resistant postpartum mania. We report on a patient with a history of bipolar disorder who developed puerperal psychosis during delivery, which ultimately responded to oral estrogen replacement therapy.

The patient is a 29-year-old woman with a history of bipolar illness since adolescence. She has had multiple inpatient admissions and past treatment included mood stabilizers, antipsychotics, and antidepressants. However, she has been stable for 8 years on a regimen of valproate and haloperidol and, with consent from her physicians, she stopped all psychotropic medications before becoming pregnant. She did relatively well through her pregnancy until the beginning of labor when she became aggressive, abusive, and psychotic. The infant was born healthy. Two days after delivery, the patient was admitted to an inpatient psychiatric unit where she continued to exhibit irritability, decreased sleep, emotional outbursts, and argumentative, intrusive behavior. Positive and Negative Syndrome Scale (PANSS) showed a Positive score of 28 (T-score=63), Negative score of 35 (T-score=71) and General Psychopathology score of 53 (T-score=64). Total PANSS score was 116, which is consistent with moderately severe illness.5 The patient was immediately started on her previous mood stabilizer and antipsychotic—valproate and haloperidol—at increasing doses over 2 months. When these medications did not help, a 6-month trial of clozapine, up to 600 mg/d, was started, followed by 2 series of 15 electroconvulsive therapy treatments. She responded to each of these treatment modalities for a few days, but would then become manic. She was again placed on valproate and haloperidol with augmentation trials of paliperidone, 6 mg/d, then lamotrigine, 200 mg/d, but she did not improve over the next 3 months. Her luteal phase serum estradiol level was 24 pg/mL, (reference range = 43.8 to 211 pg/mL) and she was started on oral conjugated estrogen, 0.625 mg/d, with no other change in medication regimen. Her psychiatric symptoms improved within 2 weeks of initiating estrogen treatment. After 1 month, the patient developed milder hypomanic mood and serum estradiol level was found to be improved, but still low at 38 pg/mL. Her conjugated estrogen dose was doubled and she has remained symptom free for 13 weeks.

It could be argued that this patient improved for reasons other than estrogen therapy, but this is unlikely for several reasons. No other medications were added or adjusted within the 2 months before she finally became symptom free. Secondly, when her mood stabilizers and antipsychotics were adjusted, improvement was less robust and did not last for more than 7 to 14 days. Third, based on research examining the disease course of bipolar disorder, spontaneous change to a euthymic or depressed state should have occurred within 3 to 6 months,6 rather than at month 13. Estrogen’s role in affective disorders has long been thought to be important, but the mechanism is poorly understood. A preliminary clinical trial of adjunctive oral contraceptive pills containing estrogen and synthetic progestin prevented premenstrual breakthrough depression in women taking antidepressants.7 There is a need for more molecular, clinical, and imaging studies looking at the effect of estrogen in postpartum affective disorders.

DISCLOSURES: The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.


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  2. Ahokas A, Aito M, Rimón R. Positive treatment effect of estradiol in postpartum psychosis: a pilot study. J Clin Psychiatry. 2000;61:166–169.
  3. Sichel DA, Cohen LS, Robertson LM, et al. Prophylactic estrogen in recurrent postpartum affective disorder. Biol Psychiatry. 1995;38:814–818.
  4. Huang MC, Wang YB, Chan CH. Estrogen-progesterone combination for treatment-refractory post-partum mania. Psychiatry Clin Neurosci. 2008;62:126.
  5. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–276.
  6. Angst J, Selloro R. Historical perspectives and natural history of bipolar disorder. Biol Psychiatry. 2000;48:445–457.
  7. Joffe H, Petrillo LF, Viguera AC, et al. Treatment of premenstrual worsening of depression with adjunctive oral contraceptive pills: a preliminary report. J Clin Psychiatry. 2007;68:1954–1962.

CORRESPONDENCE: Yokesh Balaraman, MBBS, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA, E-MAIL: ybalaram@iupui.edu