The estrogen estradiol, in combination with antipsychotic medications, appears to improve treatment for women with schizophrenia, according to an article releasedon August 4, 2008 in Archives of General Psychiatry, one of the JAMA/Archives journals.

Previously, mental illness has been studied in conjunction with many different hormones, especially estrogen in women. However, the use of estrogen as a therapy for these diseases has only gained focus recently. According to the authors, "Epidemiologic observations of sex differences in the onset and course of schizophrenia prompted exploration of estrogen's role in schizophrenia." Estradiol is the member of the estrogen family best represented in the human body. While it is usually associated with female secondary sex characteristics, both males and females maintain levels of estradiol.

To explore this association, Jayashri Kulkarni, M.B.B.S., M.P.M., F.R.A.N.Z.C.P., Ph.D., of The Alfred and Monash University and The Alfred Hospital, Melbourne, Australia, and colleagues performed a randomized, double blind study in women of child-bearing age with schizophrenia. A total 102 women were randomly assigned to one of two groups, receiving the following in combination with their regular medication regimens: 100 micrograms of estradiol via a skin patch, or a placebo skin patch. The patients were evaluated for psychotic symptoms, including hallucinations and delusions, using a standard scale.

After examination, it was found that in combination with the regular the estradiol group showed improvement in their psychotic symptoms in comparison to the group taking the placebo. However, there was also a decline in the displayed positive symptoms, representing a loss or distortion of normal functions. In light of this, the two groups had similar rates of negative symptoms, which might occur when normal functions are diminished.

The authors suggest some potential mechanistic explanations for this relationship: "Estrogen's neuroprotective and psychoprotective actions may be mediated by a variety of routes, ranging from rapid actions, including antioxidant effects and enhancement of cerebral blood flow and cerebral glucose utilization, to slower, genomic mechanisms, which may include permanent modification of neural circuits." They continue, focusing on the negative symptoms experienced by the women. "The lack of effect for negative symptoms is consistent with literature reporting that negative symptoms are less responsive to treatment than other symptoms of schizophrenia. It is possible that longer-term treatment is required for negative symptoms to respond to treatment. Alternatively, brain regions implicated in negative symptoms may be less responsive to gonadal hormone effects." 

The authors note that this therapy might be especially effective for women affected by schizophrenia who undergo hormonal changes, which seem to cause deterioration of their conditions. Examples of events that could cause this are childbirth and menopause. The authors conclude: "Estrogen treatment is a promising new area for future treatment of schizophrenia and potentially for other severe mental illnesses."

Estrogen in Severe Mental Illness: A Potential New Treatment Approach
Jayashri Kulkarni; Anthony de Castella; Paul B. Fitzgerald; Caroline T. Gurvich; Michael Bailey; Cali Bartholomeusz; Henry Burger
Arch Gen Psychiatry. 2008;65(8):955-960.
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Anna Sophia McKenney

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