Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy

Hill, Martin; Zárubová, Jana; Marusič, Petr; Vrbíková, Jana; Velíková, Marta; Kancheva, Radmila; Kancheva, Lyudmila; Kubátová, Jana; Dušková, Michaela; Zamrazilová, Ludmila; Kazihnitková, Hana; Šimůnková, Kateřina; Stárka, L.

doi:10.1016/j.jsbmb.2010.06.003

Cited by 18 publications

(3 citation statements)

References 68 publications

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“…The meta-regression analyses did not show significant moderating effects of lithium or other mood stabilizers' use on the HPA axis. Consistently, in previous reports, valproate and carbamazepine were not associated with changes in HPA axis activity in epileptic patients (Hill et al 2010).…”

Section: Findings From Meta-regression and Subgroup Analyses: Moderat...supporting

confidence: 92%

The HPA axis in bipolar disorder: Systematic review and meta-analysis

Murri

Prestía

Mondelli

et al. 2016

Psychoneuroendocrinology

289

158

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Section: Findings From Meta-regression and Subgroup Analyses: Moderat...supporting

confidence: 92%

The HPA axis in bipolar disorder: Systematic review and meta-analysis

Murri

Prestía

Mondelli

et al. 2016

Psychoneuroendocrinology

289

158

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“…Corroborating previous studies, with similar sample numbers of subjects [30], we also observed a lower DHEA‐S concentration in CBZ users. Recently, CBZ was reported to have no effect on the serum concentration of this hormone [40]. However, in such study, DHEA‐S concentrations were measured in a subset of study subjects.…”

Section: Discussionmentioning

confidence: 94%

Altered Sexual and Reproductive Functions in Epileptic Men Taking Carbamazepine

Reis¹,

Angelo²,

Sakamoto³

et al. 2013

The Journal of Sexual Medicine

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Introduction Epileptic men may experience hormonal changes that may alter semen quality and sexual function. Alterations in male sexual and reproductive parameters may also be due to treatment with antiepileptic drugs to control seizures. Aims To evaluate serum hormone concentrations, semen quality, the frequency of sexual intercourse (FSI), and erectile function in men with epileptic seizures controlled by carbamazepine (CBZ). Main Outcome Measures The five-question form of the International Index of Erectile Function (IIEF-5), and semi-structured questionnaire. Methods One hundred and eighteen men, aged 18–45 years, were included in this controlled, cross-sectional study: 63 men taking CBZ (epileptic group) were compared to 55 healthy men (control group). Blood sample was collected to determine hormones concentrations. Erectile function and the frequency of sexual relations were assessed by using questionnaires. Sperm morphology was analyzed by examining the quality of the head, intermediate part and tail of the spermatozoa. Results Using the IIEF-5, we observed a significant association between erectile dysfunction (ED) and groups (P < 0.01), where epileptic men had 17.33 (95% CI 3.59, 83.52) odds to have erectile dysfunction. Adjusted odds ratio to group considering luteinizing hormone, prolactin, Serum total testosterone, androstenedione, and dehydroepiandrosterone, androstenedione levels and free androgen index, we observed only group effect where epileptic men had 10.47 (95% CI 2.75, 39.83) odds to have FSI < 3 times a week. Sperm vitality was altered in 27% of the epileptic subjects compared with 5.4% of the control group (P < 0.002). Sperm motility differed significantly between groups, with A + B motility ≤50% observed in 98.4% of the epileptic group and in 85.4% of the control group (P < 0.01). Sperm morphology <14% was observed in 93.7% of the epileptic men, compared with 34.6% of the controls (P < 0.001). CBZ users, showed less sexual intercourse then controls (P ≤ 0.001). Conclusions Epileptic men taking CBZ present with changes in hormonal levels, altered semen quality, ED, and a reduction in coital frequency.

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“…The subsequent metabolism to individual pregnanolone isomers is provided by a system of subfamily 1C aldoketoreductases (AKR1Cs) and 17β-hydroxysteroid dehydrogenases (HSD17Bs) ( Miller and Auchus, 2011 ; Rižner and Penning, 2014 ; He et al, 2019 ) previously known as 3α- and 3β-hydroxysteroid oxidoreductases. Reduced metabolites of progesterone exert anxiolytic, sedative, hypnotic and anticonvulsive effects ( Frye, 1995 ; Klein and Herzog, 1998 ; Hill et al, 2010 ).…”

Section: Unconjugated Steroidsmentioning

confidence: 99%

Steroid Sulfation in Neurodegenerative Diseases

Vítků

Hill

Kolátorová

et al. 2022

Front. Mol. Biosci.

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Steroid sulfation and desulfation participates in the regulation of steroid bioactivity, metabolism and transport. The authors focused on sulfation and desulfation balance in three neurodegenerative diseases: Alzheimer´s disease (AD), Parkinson´s disease (PD), and multiple sclerosis (MS). Circulating steroid conjugates dominate their unconjugated counterparts, but unconjugated steroids outweigh their conjugated counterparts in the brain. Apart from the neurosteroid synthesis in the central nervous system (CNS), most brain steroids cross the blood-brain barrier (BBB) from the periphery and then may be further metabolized. Therefore, steroid levels in the periphery partly reflect the situation in the brain. The CNS steroids subsequently influence the neuronal excitability and have neuroprotective, neuroexcitatory, antidepressant and memory enhancing effects. They also exert anti-inflammatory and immunoprotective actions. Like the unconjugated steroids, the sulfated ones modulate various ligand-gated ion channels. Conjugation by sulfotransferases increases steroid water solubility and facilitates steroid transport. Steroid sulfates, having greater half-lives than their unconjugated counterparts, also serve as a steroid stock pool. Sulfotransferases are ubiquitous enzymes providing massive steroid sulfation in adrenal zona reticularis and zona fasciculata.. Steroid sulfatase hydrolyzing the steroid conjugates is exceedingly expressed in placenta but is ubiquitous in low amounts including brain capillaries of BBB which can rapidly hydrolyze the steroid sulfates coming across the BBB from the periphery. Lower dehydroepiandrosterone sulfate (DHEAS) plasma levels and reduced sulfotransferase activity are considered as risk factors in AD patients. The shifted balance towards unconjugated steroids can participate in the pathophysiology of PD and anti-inflammatory effects of DHEAS may counteract the MS.

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Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy

Cited by 18 publications

References 68 publications

The HPA axis in bipolar disorder: Systematic review and meta-analysis

The HPA axis in bipolar disorder: Systematic review and meta-analysis

Altered Sexual and Reproductive Functions in Epileptic Men Taking Carbamazepine

Steroid Sulfation in Neurodegenerative Diseases

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