Sexual function, bioavailable testosterone levels, and gonadal efficiency in men with epilepsy who took lamotrigine were comparable to control and untreated values and significantly greater than with carbamazepine or phenytoin treatment.

Summary: Purpose:We compared sexual function and reproductive hormone levels among men with localization-related epilepsy (LRE) taking various antiepileptic drugs (AEDs) and normal controls (NC).Methods: Subjects were 63 men with LRE [enzyme-inducing (EI) AEDs, 36; lamotrigine (LTG), 18; no AEDs, 9] and 18 NC. Sexual interest and function (S-score), hormone levels [bioactive testosterone (BAT) and estradiol (BAE)], hormone ratios [BAT/BAE], and gonadal efficiency [BAT/luteinizing hormone (LH)] were compared among the groups.Results: S-scores, BAT levels, BAT/BAE, and BAT/LH were significantly lower in the EIAED group than in NC or LTG groups. Sex hormone-binding globulin (SHBG) was significantly higher in the EIAED group than in all other groups. Of men with LRE, 23.8% had abnormally low S-scores: 33.3% taking EIAEDs, 5.5% taking LTG, and 22.2% taking no AEDs (p < 0.01). BAT was low in 55.6% taking EIAEDs as compared with 33.3% taking LTG and 33.3% taking no AEDs (p < 0.05). Among men with low S-scores, 86.7% had low BAT as compared with 33.3% of men with normal scores (p < 0.01). BAT decline with age was greater among men with LRE than in controls (3.75 vs. 1.80 ng/dl/yr). The slope showed no significant difference among LRE groups. However, 89% of 40-to 50-year-old men taking EIAEDs had low BAT as compared with 33% taking LTG and 33% taking no AED (p < 0.01).Conclusions: Sexual function, BAT levels, BAT/BAE, and gonadal efficiency are greater with LTG than with EIAED. Abnormally low BAT levels are reached at an earlier age with EIAEDs than with LTG.

The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle.

Summary:Purpose: 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. Key Words: Epilepsy-Reproductive-NeurosteroidsEndocrine-Men.Sexual dysfunction is unusually common among men with epilepsy and has been related to hypogonadism (Herzog et al., 2005). Androgens play an important role in sexual function (Herzog et al. 2005). Androgens also have precursors and metabolites that can influence neuronal excitability and seizures (Paul and Purdy, 1992;Rhodes and Frye, 2004;Smith, 1989;Wong and Moss, 1992). Dehydroepiandrosterone, a weak androgen, becomes highly neuroexcitatory when it is metabolized to a sulfated ester dehydroepiandrosterone sulfate (DHEAS) (Paul and Purdy, 1992). Aromatization of testosterone (T) produces estradiol (E), a highly neuroexcitatory steroid (Smith, 1989;Wong and Moss, 1992). Reduction of testosterone produces androstanediol (AL), a potent inhibitory GABAergic steroid (Rhodes and Frye, 2004).Some antiepileptic drugs (AEDs) alter the synthesis, binding, and metabolism of androgens (Herzog et al., ). This may result in different levels and ratios of excitatory and inhibitory neuroactive steroids. A systematic comparison of the effects of various AEDs on neuroactive steroids could help identify the mechanisms by which AEDs might act to suppress seizures. This investigation compared the effects of various AEDs on sexual function, reproductive steroids and some neuroactive precursors and metabolites of androgens in men with localization-related epilepsy (LRE) and normal controls (NC). Effects on sexual function and bioactive testosterone (BAT) were published previously (Herzog et al., 2005) and will be reviewed solely to place the current neuroactive steroid findings in context. METHODS Study design and subjectsThe study design was an unrandomized, observ...

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