Research on female sex hormones has demonstrated that estrogen aggravates epileptogenesis. Theoretically, this means that the frequency of epileptic attacks should be decreased in epileptic women during menopause. However, although epilepsy attacks are reported to decrease in some women during menopause, they may not change in others. Increases in attack frequency have even been reported during menopause in some epileptic women. This study has investigated the effects of estrogen, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) on caffeine-induced epileptiform activity in rats. Estrogen was found to increase epileptiform activity in a dose-dependent manner via its own receptors. In contrast, progesterone had no effect on epileptiform activity. FSH and LH suppressed epileptiform activity at low doses; however, at high doses they enhanced it. In conclusion, we suggest that the occurrence or aggravation of epilepsy, despite estrogen deficiency in the menopausal or post-menopausal period, is related to excessive accumulation of FSH and LH.