Sex Differences in Steroid Levels and Steroidogenesis in the Nervous System: Physiopathological Role

November 2019 in “ Frontiers in Neuroendocrinology ”

Silvia Giatti, Silvia Diviccaro, Melania Maria Serafini, Donatella Caruso, Luis M. García‐Segura, Bárbara Viviani, Roberto Cosimo Melcangi

neuroactive steroids neurosteroidogenesis progesterone neurosteroidogenic enzymes neuroinflammation

TLDR Men and women have different levels and production of brain steroids, which may affect their risk for certain brain disorders.

The document from 2020 discussed the role of neuroactive steroids in the nervous system, highlighting that their synthesis and levels show sex differences. It was found that neurosteroidogenesis is a sexually differentiated process, with brain progesterone levels and its metabolites being higher in pseudopregnant female rats than in males. The document also noted that neurodegenerative and psychiatric disorders show sex differences in incidence, with Alzheimer's disease and Multiple Sclerosis being higher in females, while Parkinson's disease and stroke are higher in males. Altered levels of neuroactive steroids and neurosteroidogenic enzymes were detected in post-mortem brain tissue of Alzheimer’s disease patients. The document concluded that neuroactive steroids represent promising protective agents for neurodegenerative and psychiatric disorders, and suggested neuroinflammation as a possible target for sex-specific therapy based on neuroactive steroids.

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Research cited in this study

research Relationships Between Cerebrospinal Fluid GABAergic Neurosteroid Levels and Symptom Severity in Men with PTSD

research 5alpha-Reductase Inhibitors Dampen L-DOPA-Induced Dyskinesia via Normalization of Dopamine D1-Receptor Signaling Pathway and D1-D3 Receptor Interaction

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research Repurposing Steroidogenesis Inhibitors for the Therapy of Neuropsychiatric Disorders: Promises and Caveats

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research The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats

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research Effect of the 5α-Reductase Enzyme Inhibitor Dutasteride in the Brain of Intact and Parkinsonian Mice

research Neuroactive Steroid Levels and Psychiatric and Andrological Features in Post-Finasteride Patients

research Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss

research TSPO Activation Modulates the Effects of High Pressure in a Rat Ex Vivo Glaucoma Model

research An Observational Retrospective Evaluation of 79 Young Men with Long-Term Adverse Effects After Use of Finasteride Against Androgenetic Alopecia

research Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research

research Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

research The 5α-Reductase Inhibitor Dutasteride but Not Finasteride Protects Dopamine Neurons in the MPTP Mouse Model of Parkinson’s Disease

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research Patients Treated for Male Pattern Hair Loss with Finasteride Show Altered Levels of Neuroactive Steroids in Cerebrospinal Fluid and Plasma After Discontinuation

research Dutasteride Reduces Alcohol’s Sedative Effects in Men in a Human Laboratory Setting and Reduces Drinking in the Natural Environment

research Neuroactive Steroid Levels Are Modified in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology

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