Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy.
Only limited data is available concerning the role of unconjugated Δ(5) C19-steroids and almost no data exists regarding the neuroactive C21 and C19 3α-hydroxy-5α/β-metabolites in men with epilepsy. To evaluate the alterations in serum neuroactive steroids and related substances in adult men with epilepsy on valproate and carbamazepine monotherapy, we have measured 26 unconjugated steroids, 18 steroid polar conjugates, gonadotropins and sex hormone binding globulin (SHBG) in 6 and 11 patients on valproate and carbamazepine monotherapy, respectively, and in 19 healthy adult men, using the GC-MS and immunoassays. Decreased testosterone, free androgen index, free testosterone, androstenediol, 5α-androstane-3α,17β-diol (androstanediol), androsterone, epiandrosterone, DHEA, 7β-hydroxy-DHEA, and DHEAS levels were associated with epilepsy per se. Valproate (VPA) therapy increased 5α-dihydrotestosterone, androsterone, epiandrosterone, DHEA, DHEAS, and 7β-hydroxy-DHEA levels. Decrease in pregnenolone and 17-hydroxypregnenolone were associated with epilepsy with no effect of antiepileptic drugs (AEDs). Alternatively, the increase in progesterone levels was linked to epilepsy and VPA further increased progesterone levels. Reduced steroid 20α-hydroxy-metabolites and cortisol were connected with epilepsy without an effect of AEDs. Carbamazepine induced only slight decrease in isopregnanolone, 5α,20α-tetrahydroprogesterone, and androstanediol levels.
Hill
Martin
M
Institute of Endocrinology, Národní třída 8, Prague 1 CZ 116 94, Czech Republic. mhill@endo.cz
Zárubová
Jana
J
Marusič
Petr
P
Vrbíková
Jana
J
Velíková
Marta
M
Kancheva
Radmila
R
Kancheva
Lyudmila
L
Kubátová
Jana
J
Dušková
Michaela
M
Zamrazilová
Ludmila
L
Kazihnitková
Hana
H
Simůnková
Kateřina
K
Stárka
Luboslav
L
D000328:Adult; D000731:Androstanes / Q000097:blood; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D008401:Gas Chromatography-Mass Spectrometry; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D008297:Male; D011284:Pregnenolone / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013256:Steroids / Q000097:blood* / Q000378:metabolism; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood; D014635:Valproic Acid / Q000627:therapeutic use*
D000731:Androstanes; D000927:Anticonvulsants; D006062:Gonadotropins; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; D002220:Carbamazepine; D013739:Testosterone; D014635:Valproic Acid; D011284:Pregnenolone