Menstrual cycle effects on cortical excitability.
OBJECTIVE
To determine whether there are menstrual cycle-related effects on cortical excitability in normal women.


BACKGROUND
Ovarian steroid hormones affect neurotransmission in the brain. Data from animal experiments have shown that progesterone metabolites enhance the action of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cortex, producing benzodiazepine-like (e.g., diazepam and lorazepam) physiologic and behavioral effects. Estradiol has excitatory effects on measures of neuronal excitability, 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 detect the effects of GABAergic and glutamatergic drugs in humans. We used this method to measure the effects of the menstrual cycle in normal women.


METHODS
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 tested by measuring the response to a second suprathreshold test pulse and comparing it with the response elicited by the test pulse administered alone.


RESULTS
Conditioning TMS produced more inhibition in the luteal phase than in the follicular phase (p = 0.01), of similar magnitude to the reported effect of benzodiazepine drugs.


CONCLUSIONS
This study provides the first direct evidence of changes in the excitability of a cortical network with the menstrual cycle. The results also show a potential confound for studies using transcranial magnetic stimulation in populations that include menstruating women.
Smith
M J
MJ
National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Keel
J C
JC
Greenberg
B D
BD
Adams
L F
LF
Schmidt
P J
PJ
Rubinow
D A
DA
Wassermann
E M
EM
D000328:Adult; D002540:Cerebral Cortex / Q000502:physiology*; D004574:Electromagnetic Fields; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D009044:Motor Cortex / Q000502:physiology; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D011374:Progesterone / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012016:Reference Values; D009435:Synaptic Transmission / Q000502:physiology*
D012739:Gonadal Steroid Hormones; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011374:Progesterone