Transcranial magnetic stimulation across the menstrual cycle: what do hormones have to do with it?

Commentary The authors have performed a beautiful study of transcranial magnetic stimulation (TMS) in the follicular and luteal phases of the menstrual cycles of a small group of healthy nonepi-lepsy women (n = 20) and a much larger group of women with epilepsy (n = 171) and found some controversial results. Both groups were evaluated during either ovulatory or anovulatory cycles; it appears data were used for only one cycle per subject. The epilepsy group was divided into mutually exclusive multiple endocrinological and neurological categories: generalized versus partial epilepsy, and type of catamenial seizure pattern (C1–3) if any and ovulatory versus anovulatory. Most of the epilepsy group were highly refractory, having on average 6 seizures per month, with a minimum of 2 per month. However, a subset of the epilepsy group (n = 36) were seizure free for at least 1 year. The findings presented in this study are counterintuitive according to current conceptions of reproductive neurosteroid activity yet extremely thought-provoking about brain excit-ability in epilepsy assessed by TMS. The authors found no differences in cortical excitability when comparing ovulatory versus anovulatory cycles in any groups, including healthy nonepilepsy controls. This lack of difference therefore includes women who reported catamenial seizure patterns, women with seizures or without seizures and, most importantly, women with low, normal, or high estrogen or progesterone levels, depending on the ovulatory status for the cycle studied. The hormone levels reported were consistent with the ovulatory status; indeed, an anovulatory cycle was defined as a midluteal progesterone level of <5 ng/ml. By way of background, TMS techniques such as central motor conduction time, the threshold and amplitude of motor evoked potentials allow the evaluation of motor conduction in the central nervous system. Advanced TMS applications used in epilepsy research include evaluation of brain excitability by deriving the cortical silent period length after motor stimulation , as well as paired-pulse stimulation that allows assessment of intracortical facilitation, generally thought to be glutamate-mediated activity, and intracortical inhibition, generally attributed to GABAA mediated-inhibition (1). Reproductive hormones have little to do with TMS variation across the menstrual cycle according to these data. The authors have summarized previous studies nicely and presented those results that differ from their own: Hattemer et al. in 2006 reported an increase in excitability (decreased inhibition) OBJECTIVE: We used transcranial magnetic stimulation to determine menstrual cycle-related changes in cortical excit-ability in women with and without catamenial epilepsy …