Schizophrenia, a mental disorder characterized by abnormal behavior, strange speech and a decreased ability to understand reality, is a frightening disease not only for the patient but especially to family members. The victim looks normal, but he or she has symptoms ranging from false beliefs, hallucinations and delusions to reduced social engagement and emotional expression, lack of motivation and disorganized thinking and speech.
The causes of schizophrenia, which affect between 0.3% to 0.7% of populations at some time during their lifetimes, are both genetic and environmental. There are an estimated 25 million causes around the world. Males are more likely to suffer from schizophrenia than females. While some patients recover, about half suffer from it throughout their lives.
The main treatment given to patients is antipsychotic medication, along with counselling, job training, and social rehabilitation. Some do not respond to medication, posing risk to self or others and sometimes involuntary hospitalization.
Over the years, many theories have been proposed explaining schizophrenia, and studies tested drugs based on these theories. Some showed improvement in symptoms, but these positive findings were often not later replicated, and the theory was discarded. Since 2004, several studies performed in Australia by Dr. Jayshri Kulkarni showed positive effects of estrogen patches on symptoms in women with schizophrenia.
But now, Israeli researchers and colleagues at Sheba Medical Center at Tel Hashomer near Tel Aviv, the Tel Aviv University School of Medicine, in the US and in the Republic of Moldova have carried out an independent replication study, which was recently published in the journal JAMA Psychiatry under the title “Effect of adjunctive estradiol on schizophrenia among women of childbearing age: A randomized controlled trial.” It was funded by the Stanley Medical Research Institute, a non-profit, charitable organization based in Washington DC.
This study, led by Sheba’s Dr. Mark Weiser, is regarded as a “breakthrough in schizophrenia research” because it is an independent replication, emphasizes differences in schizophrenia between women and men, indicates further study of estrogen in schizophrenia and encourages development of new compounds which bind estrogen receptors in the brain.
The researchers, who administered estrogen patches (transdermal estradiol) to 200 pre-menopausal women with schizophrenia for eight weeks, reported improvements in positive symptoms (delusions and hallucinations) and negative symptoms (lack of initiative, poor social abilities). The women continued to receive their anti-psychotic medicine while using the patches, while a control group had a placebo instead of an effective patch.
More women in the estradiol group reported breast discomfort and weight gain, but no other adverse event differed significantly between them, the researchers wrote.
The beneficial effects were most dramatic in women between the ages of 38 to 45. The authors said they had “not anticipated this age finding, however, it does fit with the epidemiological data finding the onset of schizophrenia is 2-4 years later in women than in men, and women have a lower incidence of schizophrenia until ages 35 to 44, after which women start to have an increased incidence. Moreover, women are more likely to have their first schizophrenic episode during an estradiol trough in the menstrual cycle.”
Estradiol can be an effective treatment for schizophrenia, the researchers concluded. “These results should be viewed in the context of the differences in the natural course of schizophrenia between females and males.”
Future studies, they suggested should be conducted to look at the safety of giving estradiol to premenopausal women, as the patch increases the risk of thromboembolic events, which are rare but serious complications.