Abstracts

Rationale: Antiepileptic drugs may affect reproductive endocrine function. Carbamazepine (CBZ) has well-known enzyme inducing effects increasing sex steroid binding hormone (SHBG) and reducing free androgen index (FAI), while no endocrine effects have been reported for lamotrigine (LTG). Studies in female rats and pigs have recently indicated reproductive endocrine effects of levetiracetam (LEV). It is now essential to investigate this further in humans. The aim of this study was to investigate possible differences in reproductive endocrine function in epilepsy patients using either LTG, CBZ or LEV as monotherapy, and to compare the results with healthy controls. Methods: 133 male and 68 female epilepsy patients, and 80 controls (36 males, 44 females) aged 18 to 45 years from Norway and Austria were included. They had been on LEV (32 males, 18 females), CBZ (63 males, 20 females) or LTG (38 males, 30 females) as monotherapy for at least 6 months. Hormone levels were monitored in serum. Results: For males there were no significant changes when comparing LEV or LTG to the controls, except regarding androstenedione, which was reduced in all treatment groups. The CBZ users had reduced FAI (P<0.001), increased SHBG (P<0.001) and dehydroepiandrosterone (DHEAS) (P<0.001) compared to controls. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were also increased in CBZ treated men (P>0.001 and 0,003, respectively). For females, there was a significant decrease in FAI and progesterone after CBZ treatment (P=0.009 and P<0.001, respectively). DHEAS was increased in women on LTG (P=0.012). No endocrine changes were found on LEV. Conclusions: We did not find specific endocrine side effects in LTG- or LEV-treated males. CBZ increased SHBG and reduced FAI as expected, but there were also significant changes in FSH and LH. In males, the control group had higher androstenedione levels than each of the different treatment groups. This might reflect differences between patients and healthy controls, more than specific drug induced effects. For women, our results confirm older studies regarding CBZ. No hormonal changes were found in LEV treated women. The study was funded by Glaxo Smith Kline