Differential effects of antiepileptic drugs on neuroactive steroids in men with epilepsy.
OBJECTIVE
To compare serum levels of neuroactive steroids among men with epilepsy who take various antiepileptic drugs, untreated men with epilepsy and normal controls (NC).


METHODS
Subjects were 85 men with localization-related epilepsy [unmedicated >6 months (No Rx)-10, carbamazepine (CBZ)-25, phenytoin (PHT)-25, lamotrigine (LTG)-25] and 25 NC. Sexual function scores (S-Score), hormone levels [dehydroepiandrosterone sulfate (DHEAS), bioactive (BA) testosterone (T), estradiol (BAE), and androstanediol (BAL)] and the ratios of inhibitory to excitatory neuroactive metabolites of T, i.e., BAL/BAE, were compared among groups.


RESULTS
S-scores, DHEAS, and bioactive testosterone (BAT) were significantly (p < 0.05) lower and BAL and BAL/BAE were significantly higher among CBZ and PHT groups than among NC and LTG groups. LTG did not differ from NC in any of these measures. BAT correlated significantly with BAL/BAE for PHT (r = 0.44, p = 0.02) and CBZ (r = 0.42, p = 0.03) but not for NC (r = 0.03, p = NS) and LTG (r = 0.06, p = NS) groups.


CONCLUSIONS
In comparison to LTG, enzyme inducing AEDs (CBZ, PHT) are associated with a more favorable neuroactive steroid balance (lower DHEAS and higher BAL/BAE) for seizure management, but at the expense of reduced serum bioavailable testosterone levels and sexual function.
Herzog
Andrew G
AG
Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. aherzog@bidmc.harvard.edu
Drislane
Frank W
FW
Schomer
Donald L
DL
Pennell
Page B
PB
Bromfield
Edward B
EB
Dworetzky
Barbara A
BA
Farina
Erin L
EL
Frye
Cheryl A
CA
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood*; D000731:Androstanes / Q000097:blood; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D001682:Biological Availability; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D003687:Dehydroepiandrosterone / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D004828:Epilepsies, Partial / Q000097:blood* / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use; D020018:Sexual Dysfunctions, Psychological / Q000097:blood / Q000175:diagnosis / Q000523:psychology; D013256:Steroids / Q000097:blood*; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use
D000728:Androgens; D000731:Androstanes; D000927:Anticonvulsants; D013256:Steroids; D014227:Triazines; D002220:Carbamazepine; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D010672:Phenytoin; D000077213:Lamotrigine