A clinical trial of the effects of estrogen in acutely psychotic women. Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study. Estrogen replacement and tardive dyskinesia.
This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia. In a double-blind, placebo controlled study, conjugated estrogens (CE) (0.625 mg/day) were added to a fixed dosage of haloperidol (5 mg daily). Forty-four female inpatients with acute schizophrenia were included in the study and randomized to one of the groups; 40 patients completed the trial. They were followed for 28 days and evaluated periodically with the BPRS, Negative Symptoms Rating Scale, Simpson Angus Extrapyramidal Rating Scale and UKU rating scale. Hormonal concentrations (estradiol, estrone, progesterone, FSH, LH and prolactine) were measured at baseline and weekly throughout the trial. Both groups showed similar clinical improvement during the evaluation, although there was a trend for the CE group to show a better improvement than the placebo group (p < 0.10). Side effects and the use of anticholinergics were similar in both groups. Conjugated estrogens caused elevation only of estrone levels in the CE group; estradiol and prolactin showed a similar profile for both groups. Our negative findings regarding the antipsychotic effect of conjugated estrogens does not preclude, however, a possible efficacy of other estrogens, such as 17-beta-estradiol, in schizophrenia. A double-blind randomized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia (TD) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables. After 3 weeks of treatment, the mean Abnormal Involuntary Movement Scale (AIMS) score decreased by 38% in the estrogen group and by 9% in the placebo group; the difference between groups was marginally significant (p less than 0.10). However, the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors. There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits. The findings of this preliminary trial are consistent with the results of other human and animal investigations, and they support the need for future research to understand the role of estrogens in the neuropathology and treatment of TD.
Adjunctive estrogen with or without progesterone does not appear to offer convincing advantages over placebo. Before any more research is undertaken in this area, all completed and unpublished work should be made available in order to ensure that more trials are justified.