Interactions between antiepileptic drugs and hormones

Abstract

Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation.

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…Women with epilepsy using valproate are more likely to have an increased rate of polycystic ovary syndrome/ovaries (Hu et al, 2011;Svalheim et al, 2015).…”

“…Carbamazepine and lamotrigine do not appear to cause reproductive endocrine disorders (Svalheim et al, 2015). However, by reducing the efficacy of oral and parenteral contraceptives, carbamazepine increases the risk of unintended pregnancies.…”

Anticonvulsant and behavioral effects observed in mice following treatment with an ester derivative of ferulic acid: Isopentyl ferulate

“…Furthermore, the main problems associated with antiepileptic drugs (e.g. -carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproate) involve to exhibit some side effects such as cognitive dysfunction, ataxia, sedation, hypersensitivity or worsening of seizures [4,5].…”

<i>Astragalus polysaccharide</i> relieves reproductive toxicity in phenobarbital-treated epileptic rats

“…Epilepsy has major effects on many important aspects of human life [5]. Patients with seizures often suffer from underlying brain disease and co-morbidity with depression or other mental disorders.…”

“…mechanisms which are not well-understood [3,5]. Previous studies suggested that PB treatment should be reserved for patients with resistant disabling myoclonus and seizures [4].…”