Psychotic disorders and gonadal function: Evidence supporting the oestrogen hypothesis

Department of Clinical Psychiatry and Psychotherapy, Medical School of Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 05/2004; 109(4):269-74. DOI: 10.1046/j.1600-0447.2003.00251.x
Source: PubMed


The aim of this study was to further evaluate the oestrogen hypothesis of schizophrenia, which postulates low oestradiol levels to be a risk factor for these disorders. A possible influence of neuroleptic-induced hyperprolactinaemia was to be addressed.
Sex hormones were measured and cycle phase assessed in 50 acutely psychotic women on admission and for four consecutive weeks as well as in three control groups.
Psychotic women were more likely to be admitted during a low oestrogen phase of their cycle and exhibited markedly reduced oestradiol levels, compared with 23 healthy controls, as well as 50 women suffering from other psychiatric disorders. Oestradiol variability was reduced over the menstrual cycle in women suffering from psychotic disorders.
These results support the oestrogen hypothesis. Hyperprolactinaemia due to neuroleptic treatment does not appear to account for the findings.

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    • "More recently, case reports and clinical studies have shown that women with schizophrenia demonstrate increased symptom severity, greater relapse rates, and more hospital admissions during times of low circulating sex hormones, including the early follicular phase of the menstrual cycle, postpartum, and postmenopause [47] [48] [49] [50]. In contrast, rates of relapse are less frequent and symptom severity is reduced during times of high circulating sex hormones, including pregnancy and the mid-luteal stage of the menstrual cycle [47] [51]. For example, Hallonquist et al. [52] assessed the variation in symptom severity in female outpatients with schizophrenia during two phases of the menstrual cycle. "
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    ABSTRACT: Gender differences in schizophrenia have been extensively researched and it is being increasingly accepted that gonadal steroids are strongly attributed to this phenomenon. Of the various hormones implicated, the estrogen hypothesis has been the most widely researched one and it postulates that estrogen exerts a protective effect by buffering females against the development and severity of the illness. In this review, we comprehensively analyse studies that have investigated the effects of estrogen, in particular 17 β -estradiol, in clinical, animal, and molecular research with relevance to schizophrenia. Specifically, we discuss the current evidence on estrogen dysfunction in schizophrenia patients and review the clinical findings on the use of estradiol as an adjunctive treatment in schizophrenia patients. Preclinical research that has used animal models and molecular probes to investigate estradiol’s underlying protective mechanisms is also substantially discussed, with particular focus on estradiol’s impact on the major neurotransmitter systems implicated in schizophrenia, namely, the dopamine, serotonin, and glutamate systems.
    Full-text · Article · Aug 2015 · International Journal of Endocrinology
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    • "It increases the availability of serotonin through altering mRNA and protein levels of serotonin markers and through decreasing the degradation of serotonin [7]. Research evidence showed that estrogen has protective effects, and low estrogen levels may put women at risk of developing a psychotic disorder [8]. "
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    ABSTRACT: Prolactinomas, the most common type of pituitary tumor, can induce hyperprolactinemia and cause some psychiatric symptoms, such as anxiety, depression and even psychotic symptoms [1-3]. However, in previous case reports, no information about estrogen levels was mentioned. Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. After a dopamine agonist (Dostinex) and aripiprazole were prescribed, the patient's depressed mood remitted and her menstruation normalized. The possible mechanism of MDD induced by prolactinoma is discussed.
    Full-text · Article · Oct 2013 · General hospital psychiatry
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    • "Also, symptom variability during the menstrual cycle has been reported. Amelioration of symptoms is associated with a rise in estrogen and more clinical admissions take place during low estrogen phases (Riecher-Rossler et al., 1994; Seeman, 1996; Huber et al., 2004). There are two (related) estrogen hypotheses of schizophrenia: 1) the hypoestrogenism or deficiency hypothesis which describes (chronic) gonadal dysfunction in women with schizophrenia, and 2) the protection hypothesis which states that estrogen exerts a relative protection against schizophrenia in premenopausal women (Riecher- Rossler and Hafner, 1993; Riecher-Rossler, 2002). "
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    ABSTRACT: Background: Bone mineral density (BMD), as an indicator of cumulative estrogen exposure, may be reduced in female patients with psychotic disorder (van der Leeuw et al., 2013), possibly reflecting reduced cerebral exposure to estrogen and alterations in neuroprotective effects. To the degree that BMD is a marker of cumulative (endogenous) estrogen exposure, we hypothesized that BMD would be positively associated with cerebral gray and white matter indices. Methods: Dual X-ray absorptiometry (DEXA) and magnetic resonance (MRI) scans were acquired in fourteen female patients diagnosed with a psychotic disorder. BMD was expressed in total BMD (g/cm(2)), Z- and T-scores. Cerebral cortical thickness (CT) (as indicator of gray matter status) and fractional anisotropy (FA) (as indicator of white matter integrity) were measured and served as the dependent variables in multilevel random regression models. BMD measures were the independent variables. Results: Femoral BMD measures were positively associated with CT at trend significance (total BMD: B=0.266, 95% CI: -0.019-0.552, p=0.067; Z-score: B=0.034, 95% CI: 0.001-0.067, p=0.046; T-score: B=0.034, 95% CI: 0.000-0.068, p=0.052). There were no significant associations between femoral BMD measures and FA. Conclusions: The data suggest that in women with psychotic disorder, alterations in the neuroprotective effect of estrogen (as measured by BMD) impact cortical gray matter, but not white matter integrity. These findings merit further investigation and, if replicated, would lend support to the estrogen hypothesis of schizophrenia.
    Full-text · Article · Oct 2013 · Schizophrenia Research
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