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

ABSTRACT 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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    • "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.
    General hospital psychiatry 10/2013; 36(1). DOI:10.1016/j.genhosppsych.2013.01.010 · 2.61 Impact Factor
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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.
    Schizophrenia Research 10/2013; 150(1-1):114-20. DOI:10.1016/j.schres.2013.07.033 · 3.92 Impact Factor
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    • "Changes in sex steroids have been associated with variation in symptoms in both men and women with schizophrenia. Women with schizophrenia tend to experience less severe psychotic symptoms during periods of high oestrogen such as pregnancy and experience symptom exacerbation at times low oestrogen such as post-partum and during menopause (Hallonquist et al., 1993; Huber et al., 2004; Ko et al., 2006). Men with schizophrenia display increases in negative symptom severity with lower testosterone levels (Shirayama et al., 2002; Akhondzadeh et al., 2006; Ko et al., 2007). "
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    ABSTRACT: Background: Sex steroids such as oestrogen and testosterone are potent neurodevelopmental hormones that also play a role in neuromodulation and neuroprotection of the mature brain. Sex steroid hormones may also be involved in the pathophysiology of schizophrenia as reduced circulating sex steroid levels and changes in brain sex steroid receptors are found in people with schizophrenia compared to controls. In men with schizophrenia, recent studies have documented an inverse correlation between serum testosterone and negative symptoms. Our study sought to confirm whether men with schizophrenia had lower levels of testosterone relative to controls and to determine whether lower testosterone levels were related to higher symptom severity and impaired cognition. Method: Circulating serum hormone levels (testosterone, oestrogen, and prolactin), cognitive function and symptoms were assessed in 29 chronically ill men with schizophrenia or schizoaffective disorder. Twenty healthy men were recruited as a comparison group. A series of regression analyses were performed to determine the extent to which circulating sex steroid hormone levels predict cognition and symptoms in men with schizophrenia. Results: We did not find a significant difference in serum testosterone levels between groups. However, circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia. With the exception of an effect of oestrogen on verbal memory, circulating sex steroid levels did not predict cognitive function in healthy men. Testosterone levels were not related to positive or negative symptom severity, but testosterone influenced excitement/hostility levels in our schizophrenia sample. Conclusions: The results suggest that circulating sex steroids may modulate cognitive deficits associated with schizophrenia.
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