Circulating sex and thyroid hormones were assessed in 63 male young adults with epilepsy in the Departments of Neurology and Clinical Chemistry, University of Oulu, Finland. All therapeutic regimens that included carbamazepine and/or phenytoin were associated with low levels of circulating thyroxine (T4), free thyroxine (FT4), and dehydroepiandrosterone sulfate, and low values for the free androgen index. Phenytoin, alone or combined with carbamazepine, was associated with high serum concentrations of sex hormone - binding globulin. Hormone values were unaffected by valproate monotherapy, but the combination of carbamazepine plus valproate had the most marked effect on serum thyroid hormone levels and the free androgen index. Serum T3 concentrations were unaffected by any of the medications or combinations. Serum thyrotropin concentrations were not elevated despite low serum thyroid hormone levels. [1]

COMMENT This study supports the hypothesis that an increased metabolism of thyroid hormones in the liver is the main reason for decreased T4 and FT4 serum levels in epileptic patients receiving carbamazepine and/or phenytoin treatment. The combination of valproate and carbamazepine has the most marked effect on thyroid hormone balance and both drugs are highly bound to serum proteins. Valproate displaces T4 from its binding sites on plasma proteins thereby leading to a larger amount of T4 subject to the liver enzyme inducing properties of carbamazepine. Thyroid supplements are usually not required in patients with a low serum T4 associated with anticonvulsant drug therapy. If the free T3 and T4 are normal thyroid supplements should be withheld.

To avoid criticism of a gender bias, a reference is included to “Serum steroid hormones and pituitary function in female epileptic patients during carbamazepine therapy” [2]. In 13 female epilepsy patients receiving long-term carbamazepine (CBC) monotherapy, serum sex hormone binding globulin levels increased and dehydroepiandrosterone sulfate levels decreased during CBC treatment. Increased metabolism of steroid hormones caused by liver enzyme inducing proprerties of CBC and a direct inhibitory effect of CBC on hormone synthesis and hypothylamic function are possible explanations. Despite the many changes in the serum sex hormone balance, the patients appeared to maintain ovulatory cycles during the first year of CBC treatment.