Steroid hormones, such as
progestogens and
androgens, influence
seizures.
Progestogens and
androgens exert organizational and/or activational effects that may mitigate vulnerability to, and/or expression of, some
seizure disorders.
Progestogens, such as
progesterone (P(4)) and its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which vary across the reproductive cycle and lifespan, may protect against
seizures through actions at intracellular
progestin receptors (PRs) and membrane receptors, such as
gamma-aminobutyric acid (
GABA)(A) receptors. Similarly,
androgens, such as
testosterone (T), which also vary across the reproductive cycle and the lifespan, can have antiseizure effects. Some of these effects of T may be due to aromatization to
estrogen and/or 5alpha-reduction to
dihydrotestosterone (DHT), and its subsequent conversion through 3alpha-hydroxysteroid
dehydrogenase to 5alpha-androstane-3alpha,17alpha-diol (3alpha-diol). Sensitivity to
steroids in some individuals may be mitigated by differences in stress, developmental phase, reproductive status, endocrine status, and treatments, such as
antiepileptic drugs (AEDs), which alter levels of these
ligands and/or function of their target sites. The evidence implicating sex
steroids in differences associated with hormonal, reproductive, developmental, stress, seizure type, and/or
therapeutics are discussed.