Effects of Ovarian Hormones on Human Cortical Excitability

Ovarian steroids appear to alter neuronal function in women, but direct physiological evidence is lacking. In animals, estradiol enhances excitatory neurotransmission. Progesterone-derived neurosteroids increase GABAergic inhibition. The effect of weak transcranial magnetic stimulation of the motor cortex on the motor evoked potential (MEP) from transcranial magnetic stimulation given milliseconds later is changed by GABAergic and glutamatergic agents. Using this technique previously, we showed more inhibition in the luteal phase relative to the midfollicular menstrual phase, which is consistent with a progesterone effect. To detect the effects of estradiol, we have now divided the follicular phase. We tested 14 healthy women during the early follicular (low estradiol, low progesterone), late follicular (high estradiol, low progesterone), and luteal (high estradiol, high progesterone) phases, with interstimulus intervals from 2 to 10msec (10 trials at each interval and 40 unconditioned trials). We calculated the ratio of the conditioned MEP at each interval to the mean unconditioned MEP: the higher the ratio, the less inhibition and the more facilitation caused by the first stimulus. The combined ratios increased significantly from the early follicular phase to the late follicular phase and then decreased again in the luteal phase. These findings demonstrate an excitatory neuronal effect associated with estradiol and confirm our earlier finding of inhibition associated with progesterone.