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

Studysummary This review discusses the sex differences in neuroactive steroid synthesis and their implications for nervous system functions and potential therapeutic approaches, but it provides no new experimental results.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

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

59 citations , November 2018 in “Psychoneuroendocrinology”

This study suggests that cerebrospinal fluid levels of the neurosteroids allopregnanolone and pregnanolone correlate negatively with PTSD and negative mood symptoms, with potential sex-specific differences in synthesis enzyme blocks.

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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 Treatment of Male Rats with Finasteride, an Inhibitor of 5alpha-Reductase Enzyme, Induces Long-Lasting Effects on Depressive-Like Behavior, Hippocampal Neurogenesis, Neuroinflammation, and Gut Microbiota Composition

37 citations , September 2018 in “Psychoneuroendocrinology”

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

10 citations , May 2018 in “Neuropharmacology”

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research Post-Finasteride Syndrome and Post-SSRI Sexual Dysfunction: Two Sides of the Same Coin?

40 citations , April 2018 in “Endocrine”

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14 citations , March 2018 in “Translational Stroke Research”

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

58 citations , April 2017 in “The Journal of Steroid Biochemistry and Molecular Biology”

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

43 citations , January 2016 in “International Journal of Andrology”

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

123 citations , December 2015 in “Journal of Neuroendocrinology”

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

33 citations , December 2015 in “Neuroendocrinology”

This study found that subchronic finasteride treatment in male rats altered neuroactive steroid levels and steroid receptor expression in the brain, with some changes persisting after drug withdrawal.

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research Adverse Effects of 5α-Reductase Inhibitors: What Do We Know, Don't Know, and Need to Know?

111 citations , August 2015 in “Reviews in Endocrine and Metabolic Disorders”

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

27 citations , May 2015 in “Neuropharmacology”

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research New Steps Forward in the Neuroactive Steroid Field

31 citations , March 2015 in “The Journal of Steroid Biochemistry and Molecular Biology”

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186 citations , February 2015 in “Frontiers in Neuroscience”

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research Midazolam Ameliorates the Behavioral Deficits of a Rat Posttraumatic Stress Disorder Model Through Dual 18 kDa Translocator Protein and Central Benzodiazepine Receptor and Neurosteroidogenesis

56 citations , July 2014 in “PLoS ONE”

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

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61 citations , April 2014 in “The Journal of Steroid Biochemistry and Molecular Biology”

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73 citations , July 2013 in “The Journal of Sexual Medicine”

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research Persistent Sexual Side Effects of Finasteride: Could They Be Permanent?

112 citations , July 2012 in “The Journal of Sexual Medicine”

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research Antipsychotic-Like Properties of 5-Alpha-Reductase Inhibitors

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research Mechanism of Progesterone Neuroprotection of Rat Cerebellar Purkinje Cells Following Oxygen-Glucose Deprivation

83 citations , November 2006 in “European Journal of Neuroscience”

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research Reduced Metabolites Mediate Neuroprotective Effects of Progesterone in the Adult Rat Hippocampus. The Synthetic Progestin Medroxyprogesterone Acetate (Provera) Is Not Neuroprotective

123 citations , June 2006 in “Journal of Neurobiology”

This study reports that progesterone metabolism to DHP and THP is necessary for its neuroprotective effect against kainic acid excitotoxicity in ovariectomized rats, unlike the synthetic progestin MPA.