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Add-on Estradiol Helpful in Certain Schizophrenic Women

August 09, 2019

By David Douglas

NEW YORK—Adjunctive estradiol along with antipsychotic therapy can prompt salutary effects in women of childbearing age with schizophrenia, according to a study conducted in the Republic of Moldavia.

In a July 31 online paper in JAMA Psychiatry, Dr. Mark Weiser of Sheba Medical Center in Tel Hashomer, Israel and colleagues note that earlier studies, particularly by researchers in Australia, have shown benefits of estradiol in women and they sought to further examine these findings.

Having done so, Dr. Weiser who is also with The Stanley Medical Research Institute, Washington, DC, told Reuters Health, "This study is a breakthrough in schizophrenia research because in an independent replication, it emphasizes differences in schizophrenia between women and men, suggests further study of estrogen in schizophrenia, and encourages development of new compounds which bind estrogen receptors in the brain."

The team enrolled 200 women, ages 19 to 46 (median age, 38) and randomly assigned them to receive a 200 mcg estradiol patch or a placebo patch changed twice weekly in addition to their regular antipsychotic treatment.

The primary outcome was determined by scoring on the positive subscale of the Positive and Negative Syndrome Scale (PANSS) with a lower score indicating fewer symptoms. At baseline the PANSS total score was 83.4 in the estradiol group and 82.3 in the placebo group.

At baseline, the mean PANSS positive subscale score was 19.6 for both groups combined. At 8 weeks this score was 13.4 in the estradiol group and 14.4 in the placebo group, a significant difference. This was also the case in the secondary outcome measures of PANSS total score difference as well as the PANSS subscales for negative symptoms and general psychopathology.

Participants in both groups showed considerable symptomatic improvement. However, the beneficial effect of estradiol versus placebo was evident only in the 100 participants who were older than 38.0 years. Of this group, 54 received estradiol and 46 got placebo.

These results, the researchers observe "suggest that exogenous estrogen might become effective only when endogenous estrogen starts to diminish or when estrogen receptors become less sensitive in the menopausal transition."

As to adverse effects, breast tenderness was experienced by 15 of the estradiol group versus only one of the placebo patients. There were similar findings for weight gain which was seen in 14 estradiol patients and only one in the placebo group.

The investigators then went on to conduct a meta-analysis of the current study together with three previous studies that tested estradiol patches in women with schizophrenia and again found a positive effect.

However, they stress that further studies are needed and that the result only applies to premenopausal women receiving antipsychotics "and is not applicable to potential effects of estradiol on older women, men, or as monotherapy."

Commenting by email, Dr. Phillip Homan of the Center for Psychiatric Neuroscience at the Feinstein Institute for Medical Research, in Manhasset, New York, told Reuters Health, "Replicating previous findings in smaller samples, the reductions in positive and negative symptoms were indeed promising, and more pronounced in older women."

"This age effect," he concluded, "was surprising and should be investigated in future studies, which should then also control for illness stage (acute/chronic), menstrual status, and long-term effects."


JAMA Psychiatry 2019.

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