Hormone Therapy for Schizophrenia?

Schizophrenic women who get an estrogen patch along with their regular antipsychotic medications have fewer symptoms than women who get inactive placebo patches.

The finding, from a four-week study of 102 women of childbearing age with schizophrenia , comes from Jayashri Kulkarni, MBBS, PhD, and colleagues at Monash University in Melbourne, Australia.

During her psychiatric training, Kulkarni spoke with many schizophrenic women who kept telling her, "It's my hormones, Doc." They also told her, "No one takes any notice when I say that it's to do with my hormones."

Kulkarni took notice. She and her colleagues have now completed a series of small studies showing that estrogen can be very effective in reducing symptoms such as delusions, hallucinations, and disordered thinking.

"We are proud of the science, but the best thing is seeing the great improvement in our patients' quality of life," Kulkarni tells WebMD via email. "One woman who had been a nurse, developed schizophrenia soon after she had a baby and had the worst form of the illness. For eight years, she was more in hospital than out. She made a dramatic improvement on estrogen -- and went from being unable to even attend to her personal hygiene, constant auditory hallucinations, and paranoia to now being able to work as a clerical assistant and live independently."

Kulkarni is quick to add that one patient's experience does not prove the treatment will work for others. But she's seen rapid improvement in other women who were resistant to standard treatment, particularly those who developed schizophrenia just after having a child.

Several lines of evidence point to a major role for estrogen in schizophrenia:

• The female sex hormone estrogen has important effects on chemical signals in the brain. These signals go haywire in schizophrenia.


• Women's first episodes of schizophrenia occur later in life than men's, suggesting a protective role for estrogen.


• In women, schizophrenia symptoms often appear just after childbirth and during menopause, when estrogen levels plunge.


• Women with schizophrenia often relapse during the low-estrogen phase of their menstrual cycles.

"Estrogen is very interesting. Besides its actions as a sex hormone, it plays many roles in the brain," Ongur tells WebMD. "We are going to be seeing more of this approach, spurred on by the Kulkarni studies and other papers."

However, Ongur warns that hormone therapy with estrogen is not benign. Estrogen has effects throughout the body -- including promotion of hormone-sensitive breast and cervical cancers.

That's why Kulkarni's team is exploring the use of a class of drugs called selective estrogen receptor modulators or SERMs. The idea is to see whether these drugs can exert the same antipsychotic effect as estrogen without estrogen's side effects.

Interestingly, adding estrogen to standard treatments also seems to help men with schizophrenia. In a two-week pilot study with 52 men -- kept brief to avoid the feminizing effects of female sex hormone -- Kulkarni's team found that estrogen reduced acute schizophrenia symptoms.

The researchers now plan a larger study of SERMs in men with schizophrenia. SERM trials in women with schizophrenia also are planned. Meanwhile, Kulkarni is focusing on a three-site study of estrogen patches in schizophrenic women of childbearing age. That study is designed to ensure that the current findings aren't a fluke.

Kulkarni says she is currently using estrogen to treat schizophrenia in women -- but only with ongoing Pap smears, breast exams, blood pressure tests, and other health checks.

Ongur warns families that while estrogen appeas useful, much more work is needed to ensure that hormone therapy is both safe and effective.

"Patients and families should not be rushing to their psychiatrists and asking for estrogen patches," he says. "But they should watch the news coming out of this work carefully."

Kulkarni agrees that there's a lot more to be done before estrogen can be considered a safe addition to schizophrenia treatment .

"There is a lot to be done. But I believe that we have opened up a new and promising area of treatment for a debilitating illness in both women and men," she says.

By Daniel DeNoon
Reviewed by Louise Chang
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