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Biol Psychiatry. 2003 Oct 1;54(7):757-62.

Abnormal luteal phase excitability of the motor cortex in women with premenstrual syndrome.

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  • 1National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.



Premenstrual syndrome (PMS) involves an aberrant behavioral response to normal hormone secretion. Pathogenetic theories posit abnormal modulation of gamma-aminobutyric acid (GABA) transmission in the brain by neuroactive metabolites of progesterone (neurosteroids). In earlier transcranial magnetic stimulation (TMS) studies of the motor cortex, we showed that inhibition increases in the luteal phase, consistent with neurosteroid action at the GABA(A) receptor. Here, we studied women with PMS to see if their response to endogenous progesterone differed from that of control subjects.


We studied nine women with PMS and 14 control subjects during the midfollicular and luteal phases with paired TMS. Subthreshold conditioning TMS was followed by test stimulation that produced a motor evoked potential (MEP) in a hand muscle. We gave pairs at each of seven intervals (2-10 msec) and unconditioned stimuli, measuring the amplitude ratio of the average MEP from the pairs at each interval to that from the unconditioned stimuli (ratio < 1 = inhibition).


Both groups showed the same follicular phase response to paired TMS. Control subjects showed more inhibition in the luteal phase. Women with PMS showed relative facilitation.


This is the first physiological evidence for an abnormal brain response to progesterone in PMS.

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