Menstrual cycle effects on cortical excitability

Objective: To determine whether there are menstrual cycle-related effects o n cortical excitability in normal women. Background: Ovarian steroid hormon es affect neurotransmission in the brain. Data from animal experiments have shown that progesterone metabolites enhance the action of gamma-aminobutyr ic acid (GABA), the main inhibitory neurotransmitter in the cortex, produci ng benzodiazepine-like (e.g., diazepam and lorazepam) physiologic and behav ioral effects. Estradiol has excitatory effects on measures of neuronal exc itability, possibly acting through the glutamate system. These effects have been difficult to detect in women using conventional techniques. However, recently, paired transcranial magnetic stimulation (TMS) has been used to d etect the effects of GABAergic and glutamatergic drugs in humans. We used t his method to measure the effects of the menstrual cycle in normal women. M ethods: We tested 13 healthy women during the follicular (low-progesterone) and luteal (high-progesterone) phases of the menstrual cycle using paired TMS. The effect of a subthreshold conditioning pulse on the cortex was test ed by measuring the response to a second suprathreshold test pulse and comp aring it with the response elicited by the test pulse administered alone. R esults: Conditioning TMS produced more inhibition in the luteal phase than in the follicular phase (p = 0.01), of similar magnitude to the reported ef fect of benzodiazepine drugs. Conclusions: This study provides the first di rect evidence of changes in the excitability of a cortical network with the menstrual cycle. The results also show a potential confound for studies us ing transcranial magnetic stimulation in populations that include menstruat ing women.