Estrogen Modulation in Schizophrenia Treatment
Summary
Oestrogen exerts multifaceted effects on brain function, modulating neurotransmission, synaptic plasticity and neuroprotection in regions implicated in schizophrenia. Clinical patterns—such as reduced relapse rates during high-oestrogen phases of the menstrual cycle and a second peak of onset in women around menopause—support a protective role for 17β-oestradiol. Preclinical models demonstrate that oestrogen influences dopaminergic, serotonergic and glutamatergic pathways, buffering against psychosis-like behaviours. Adjunctive therapies employing oestrogenic compounds, notably selective oestrogen receptor modulators (SERMs) such as raloxifene, have shown promise in improving symptom severity, cognition and social functioning, while also mitigating antipsychotic-induced side effects. Personalised approaches that consider hormonal status, reproductive stage and sex-specific pharmacokinetics are emerging as vital for optimising treatment efficacy and tolerability.
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Estrogen Modulation in Schizophrenia Treatment publication trend
The graph below shows the total number of articles in estrogen modulation in schizophrenia treatment across all publications each year (not limited to Nature Index journals).
Technical terms
Oestrogen: Steroid hormones, including 17β-oestradiol, essential for reproductive health and neuroprotection.
Oestrogen receptor: Nuclear and membrane proteins that mediate genomic and non-genomic actions of oestrogens in target tissues.
Selective Oestrogen Receptor Modulator (SERM): Agents that selectively agonise or antagonise oestrogen receptors in a tissue-dependent fashion, exemplified by raloxifene.
Hyperprolactinaemia: Elevated prolactin levels often induced by antipsychotics, which can disrupt gonadal hormone balance and exacerbate symptoms.
Perimenopause: The transitional period preceding menopause, marked by fluctuating and ultimately declining ovarian oestrogen production.
References
- Evidence-Based Recommendations for the Pharmacological Treatment of Women with Schizophrenia Spectrum Disorders. Current Psychiatry Reports (2023).
- A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings. International Journal of Endocrinology (2015).
- Risk for midlife psychosis in women: critical gaps and opportunities in exploring perimenopause and ovarian hormones as mechanisms of risk. Psychological Medicine (2022).
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