Hormonal Effects of Antiepileptic Drugs are Reversible

LORENSKOG, Norway, Oct. 26 -- Common antiepileptic drugs can negatively affect reproductive endocrine function, but the changes may be reversible even after years of chronic use, investigators here reported.
In a randomized double-blind study, both men and women who were withdrawn from carbamazepine, for example, had significant increases in serum testosterone and free androgen index compared with patients who stayed on the drug, reported Morten Lossius, M.D., of Akershus University Hospital and the National Center for Epilepsy, and colleagues.
"The increase in the free androgen index found in the present study shows that the decrease in free androgen index associated with carbamazepine treatment is reversible," the authors wrote in the October issue of Epilepsia.
The study evaluated the effects of antiepileptic drug withdrawal on reproductive endocrine function -- specifically, whether the known suppressive effects of the drugs on endocrine function could be partially or fully reversible.
The investigators studied 70 men and 80 women from the ages of 18 to 67 who had epilepsy (defined as at least two unprovoked seizures) and who had been seizure-free for at least two years while on antiepileptic drug monotherapy.
The patients were randomly assigned to drug withdrawal via dose reduction and placebo substitution, or no withdrawal.
Blood samples were taken and evaluated at baseline and at four months after the time of complete withdrawal (or no withdrawal) for total testosterone, 17-beta-estradiol, progesterone, sex hormone binding globulin, follicle stimulating hormone, luteinizing hormone, free androgen index, insulin, estradiol/sex hormone binding globulin ratio and C-peptide.
Complete before-and-after serum samples for 130 patients were available for analysis at the end of the one-year study.
"The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of antiepileptic drugs," the authors wrote.
Patients assigned to carbamazepine withdrawal had significant increases in serum testosterone concentrations (P=0.001) and free androgen index in both men and women (19 in each group).
Mean differences in change in the free androgen index between the withdrawal group and nonwithdrawal group were 17.49 (95% confidence interval, 10.16 to 24.81, P ≤ 0.001) in men, and 1.61 (95% CI, 0.62-2.61, P ≤ 0.001) in women.
"Our findings provide further evidence of the potentially negative effects of carbamazepine treatment on reproductive endocrine functions in men and women, but also show that some of these changes may be reversible, even after years on treatment," the authors wrote.
The numbers of both men and women on valproic acid (Depakene, Depakote) were too small to draw statistically significant conclusions about the effects of withdrawal on endocrine levels, they noted.
Neither the study funding source nor author conflicts of interest were listed. Primary source: EpilepsiaSource reference: Lossius MI, et al "Reversible Effects of Antiepileptic Drugs on Reproductive Endocrine Function in Men and Women with Epilepsy-A Prospective Randomized Double-blind Withdrawal Study." Epilepsia 48; 10: 1875-1882.