There is cumulative evidence suggesting that estrogen might play a role in the development of schizophrenia and therefore may be useful in the treatment of this illness. On average, the first signs of schizophrenia appear 3 to 4 years later in women than in men, with a second peak in women around menopause.  Interestingly, men suffering from schizophrenia exacerbation demonstrate low serum estrogen and androgen levelsEstrogen has been demonstrated to have beneficial effects in treating hormonally mediated affective disorders such as postnatal depression or perimenopausal depression.  A recent study published in the Archives of General Psychiatry suggests that estrogen may also be beneficial for the treatment of patients with schizophrenia.

In this study, 102 women with the diagnosis of schizophrenia were recruited to participate in a double-blind, placebo-controlled study.  Fifty-six participants received 100 mcg estradiol transdermal patch and 46 women received a placebo patch (no active hormone present).  All women remained on their regular antipsychotic medications and were followed for 28 days. Participants’ symptoms were assessed every 7 days.  Hormone levels were measured at baseline and on day 28 of the study.

Patients receiving estrogen showed significant improvement in positive symptoms (hallucinations, delusions), but no difference in negative symptoms (reduction in range of emotional expression, poverty of speech, lack of motivation) was observed.

Although promising, this study has a few shortcomings which need to be addressed in the future.  First, variation in the menstrual cycle phase at entry into the study and variability in the baseline hormone levels may affect symptom severity. In addition, the study does not provide any information on the long-term effects of estrogen in this population.

If these initial findings are confirmed and long-term use of estrogen is proven to be safe, estrogen may have multiple future applications in this clinical population.  Estrogen might be used as an adjunctive treatment in women whose symptoms worsen during periods of hormonal change (i.e., during the luteal phase of the menstrual cycle, postpartum period or menopause).  Estrogen may also be used to augment treatment in women, and perhaps in men, who have either residual or worsening positive symptoms on standard antipsychotic medications.

Snezana Milanovic, MD, MSc

Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, Burger H. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008 Aug;65(8):955-60.

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