Gaps or links between hormonal therapy and schizophrenia? (Review) (original) (raw)
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The role of estrogen in schizophrenia
Journal of Psychiatry and Neuroscience, 1996
This paper reviews 3 recent studies from different clinics correlating psychotic symptoms with phases of the menstrual cycle in women with schizophrenia. The aim of the paper is to focus on the estrogen protection hypothesis which would suggest that low estrogen phases correlate with more severe symptoms, and high estrogen phases correlate with less severe symptoms. Although the methodology of the 3 studies was different, the hypothesis was essentially upheld. High levels of estrogens protect against symptom exacerbations in women with schizophrenia. A corollary to this finding is that, for optimal efficacy and safety, neuroleptic doses could be reduced at certain times of the month and increased at others.
Estrogen — A potential treatment for schizophrenia?
Schizophrenia Research, 2000
Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems Ð the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N 12 in each group) who received standardized antipsychotic medication plus 50 mcg transdermal estradiol or 100 mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100 mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50 mcg estradiol and placebo groups. Women receiving 50 mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100 mcg estradiol group had signi®cantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50 mcg and placebo groups. The addition of 100 mcg adjunctive transdermal estrogen signi®cantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50 mcg versus 100 mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2003
The estrogen hypothesis of schizophrenia postulates that estrogen exerts a protective effect against schizophrenia and that this partly explains the observed sex differences in premorbid adjustment, onset age, treatment response, and illness course. It has been suggested that estrogen supplementation can augment the treatment effects of antipsychotics. The purpose of the present investigation was to access the efficacy of ethinyl estradiol as an adjuvant agent in the treatment of premenopausal women with chronic schizophrenia in an 8-week, double-blind, and placebo-controlled trial. Eligible participants in the study were 32 women of childbearing age with schizophrenia. All patients were inpatients, in the active phase of illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 16 to haloperidol 15 mg/day plus ethinyl estradiol 0.05 mg/day and 16 to haloperidol 15 mg/day plus placebo for an 8-week, double-blind, placebo-controlled study. Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of haloperidol and ethinyl estradiol showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as Positive and Negative Syndrome Scale (PANSS) total scores. Although the means Extrapyramidal Symptoms Rating Scale (ESRS) for the placebo group were higher than ethinyl estradiol group, the differences were not significant over the trial. A significant difference was observed between the overall mean biperiden dosages in the two groups. The results of this study suggest that estrogen may be an effective adjuvant agent in the management of women of childbearing age with chronic schizophrenia. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be made.
The Role of Estrogens in Schizophrenia Gender Differences
Schizophrenia Bulletin, 1990
The male/female differences that have been described in schizophrenia are important because they may ultimately shed light on factors that mediate the expression of schizophrenic illness. The hypothesis of this article is that estrogens, either directly or indirectly, modify symptom expression and account for many of the observed gender differences. The role of sex hormones is divided into organizational and activational effects. Organizational effects take place during a critical period in fetal life and put a permanent stamp on the developing brain. Activational effects are the direct influences of circulating hormones that appear when hormonal levels rise, and wane when hormonal levels drop. Because levels of sex hormones in adult women fluctuate during the menstrual cycle, cyclic effects of high and low female hormones may induce specific responses by the adult female brain. All these effects have implications for genetic, environmental, pharmacological, neurocognitive, clinical, and epidemiological research in schizophrenia.
Can Estradiol Modulate Schizophrenic Symptomatology?
Schizophrenia Bulletin, 1994
Using epidemiologic data, in an earlier study we formulated the hypothesis that estrogens can delay the onset of schizophrenia in females by raising the vulnerability threshold for this disease. In animal experiments, Häfner and colleagues found evidence that chronic estradiol treatment reduces the sensitivity of dopamine (D2) receptors in the brain. In the clinical study presented in this article, as
Menstrual exacerbation of schizophrenia symptoms
Acta Psychiatrica Scandinavica, 2012
Objective: To better understand premenstrual exacerbations of schizophrenia in women and weigh treatment options. Method: A PubMed literature search was conducted, using the search terms ÔschizophreniaÕ, ÔpsychosisÕ, Ômenstrual exacerbationÕ, ÔhormonesÕ and assessing relevance to premenstrual exacerbation of schizophrenia symptoms. Results: Exacerbations are usually distinguishable from periodic or menstrual psychosis, a relatively rare condition. Controversy continues about whether low estrogen periods of the month lead to an increase in schizophrenia symptoms among women of reproductive age or whether some women suffer from both schizophrenia and premenstrual dysphoric disorder (PMDD). No treatment trials of specific interventions have been conducted so that physicians must decide on a case-by-case basis whether to raise antipsychotic doses premenstrually, try estrogens or estrogen ⁄ progesterone combinations or selective estrogen receptor modulators, or target PMDD symptoms. Conclusion: Clinicians need to be aware of premenstrual symptom aggravation in a large minority of women with schizophrenia. Treatment strategies will depend on the nature of the symptoms that are exacerbated. Optimal treatment needs to be adjusted to the individual woman.
Introduction: Gender differences in schizophrenia include the age of onset, better treatment response, a better outcome , and the peak of the disease in postmenopausal women. Some evidence indicates that these variations are due to estrogen's effect. The intention of this study was to evaluate the effectiveness of estrogen as an adjuvant agent in the treatment of women with chronic schizophrenia. Methods: Study participants were 32 women of childbearing age with chronic schizophrenia. These patients were hospitalized in an institute for the chronically mentally ill. Participants were randomized into two groups: the first group (16 cases) received conjugated estrogens 0.625 mg/day 4 weeks with their previous antipsychotic treatment, while the second group (16 cases) received placebo booster and antipsychotics. The Positive and Negative Syndrome Scale (PANSS) was used as a measurement tool for assessing psychopathology. Results: The combination of conjugated estrogens with antipsychotic treatment showed a significant decrease in positive (p=0.003), negative (p<0.001), general (p<0.001) and total (p<0.001) PANSS scores over 4 weeks. Conclusions: Estro-gen may be an effective adjuvant agent in the treatment of women with chronic schizophrenia. Abstract Introduction
Gender Differences in Schizophrenia: Hormonal Effect or Subtypes?
Schizophrenia Bulletin, 1995
Compared with their male counterparts, females with schizophrenia, on average, show better premorbid functioning, later onset, and a more benign course of illness. They are also more likely to have a family history of schizophrenia and/or affective illness, to exhibit "atypical" and affective features, and to show a seasonal pattern of hospital admission that mimics that of patients with mania. However, there exists a paradox. Although schizophrenia in females has much in common with affective disorder, the "schizophrenogenic" effect of maternal influenza also appears to be more significant in female than in male schizophrenia. Perhaps females with a predisposition to affective psychosis who have also been subject to the effects of maternal viral infection during gestation develop some subtle neurodevelopmental damage that renders their psychosis schizophrenia-like.