Estrogen levels and schizophrenia

Dr. Weeks’ Comment:  Intriguing concept but weak data. What do you think?

Estrogen in the Fight Against Schizophrenia

ScienceDaily (Jan. 25, 2010) ”” Many American women are prescribed estrogen to combat the negative effects of menopause, such as bone loss and mood swings. Now, new evidence from a Tel Aviv University study suggests that hormone replacement therapy might also protect them — and younger women — from schizophrenia as well.

Prof. Ina Weiner of Tel Aviv University’s Department of Psychology and her doctoral student Michal Arad have reported findings suggesting that restoring normal levels of estrogen may work as a protective agent in menopausal women vulnerable to schizophrenia. Their work, based on an animal model of menopausal psychosis, was recently reported in the journal Psychopharmacology.

“We’ve known for some time that when the level of estrogen is low, vulnerability to psychotic symptoms increases and anti-psychotic drugs are less likely to work. Now, our pre-clinical findings show why this might be happening,” says Prof. Weiner.

A hormonal treatment to address a behavioral condition

In their study, Weiner and Arad removed the ovaries of female rats to induce menopause-like low levels of estrogen and showed that this led to schizophrenia-like behavior. The researchers then tried to eliminate this abnormal behavior with an estrogen replacement treatment or with the antipsychotic drug haloperidol. Estrogen replacement therapy effectively alleviated schizophrenia-like behavior but haloperidol had no effect on its own. Haloperidol regained its effect in these rats when supplemented by estrogen.

“When the level of estrogen was low, we could see psychotic-like behavior in the animals. Moreover, the sensitivity to psychosis-inducing drugs went up, while the sensitivity to anti-psychotic drugs went down,” Prof. Weiner says. This is exactly what we observe in women with low estrogen levels,” she says. “But we also found that estrogen, all by itself, combats psychosis in both male and female rats.” Furthermore, in low amounts estrogen increases the effectiveness of anti-psychotic drugs.

Prof. Weiner points out that the medical community is hotly debating the pros and cons of estrogen replacement as an add-on to conventional treatment in schizophrenia. Detractors point to higher chances of cervical cancer and heart attacks in those who receive estrogen supplements. But according to her study, which looked at very specific factors possibly related to schizophrenia, estrogen replacement therapy could have positive behavioral effects, she concludes.

Assessing the possibility for prevention

During the course of a woman’s lifetime, estrogen levels do not remain constant. During her reproductive years, these levels are affected by the menstrual cycle. There are also dramatic changes in the levels of estrogen just after a woman gives birth — a change, which can trigger “post-partum blues,” and in extreme cases lead to clinical depression and psychosis.

As a preventative therapy, estrogen could be given to women at certain points in time when they are most at risk for schizophrenia, Prof. Weiner suggests: in their mid-twenties and later during the menopausal years.

“Antipsychotic drugs are less effective during low periods of estrogen in the body, after birth and in menopause,” says Prof. Weiner. “Our research links schizophrenia and its treatment to estrogen levels. Men seem less likely to begin schizophrenia after their 40s, which also suggests that estrogen is the culprit.”


Hello Brad,

Here is an excerpt regarding progesterone-head injury research by Dr. Don Stein, who has been pushing this theory for about 20 years.

Patients on progesterone had a death rate of just 13% from their head injuries, less than half the 30% death rate of those on standard treatment. And progesterone showed no negative side effects. The 100-subject study was too small to prove that progesterone caused the lowered death rate, but the findings were consistent with animal research. Dr. Stein was so elated that he had to ask his wife to take over the driving.

In the respected journal “Annals of Emergency Medicine” this past April, Dr. Stein and his researchers summarized the study: “Moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo.”

The story is still far from over. Before progesterone can be approved as a treatment, Dr. Stein’s findings must be proved in a larger study of humans. But as he and his team have persisted in research, he has himself become the mainstream of neuroscience. His animal research now has been replicated in dozens of studies at numerous research institutions.

Dr. Stein and his Emory team have applied for NIH funds to do a 1,000-patient study, which will give the definitive word. The NIH already has given an initial $229,000 grant to plan the study, but Emory hasn’t yet officially applied for the full grant. Such a trial could take five years or more. Meanwhile, Emory’s technology-transfer office is “optimistic” about developing and marketing progesterone as a treatment for brain injury, says Dr. Scherer, director of that office.

Progesterone and estrogen are evidently both neuro-protective.  I propose it is via a critical step in methylation and myelin synthesis.  Estrogen is cyclical; progesterone is more stable, therefore more reliable as a therapeutic factor in neurological injury cases.

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