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Effect of Menstrual Cycle Phase on Neuroendocrine and Behavioral Responses to the Serotonin Agonist m-Chlorophenylpiperazine in Women with Premenstrual Syndrome and Controls¹

Behavioral Endocrinology Branch (T.-P.S., P.J.S., D.R.R.), Clinical Center Nursing Department (M.D.), and Laboratory of Clinical Science (D.L.M.), National Institute of Mental Health, Bethesda, Maryland 20892-1276

Address all correspondence and requests for reprints to: David R. Rubinow, M.D., Behavioral Endocrinology Branch, National Institute of Mental Health, Building 10, Room 3N238, 10 Center Drive, MSC 1276, Bethesda, Maryland 20892-1276.

To evaluate the potential role of serotonin in the premenstrual syndrome (PMS), we investigated the effects of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonergic agent m-chlorophenylpiperazine (m-CPP) in women with PMS and controls.

A single oral dose of m-CPP (0.5 mg/kg) was administered to 10 PMS patients and 10 healthy controls during the follicular and luteal phases of the menstrual cycle. We observed the following. m-CPP administration during the luteal phase resulted in an acute improvement of PMS symptoms; the plasma cortisol and ACTH responses to m-CPP were blunted in both menstrual cycle phases in PMS patients compared with controls.

These data provide evidence for the acute efficacy of m-CPP in the treatment of PMS. Although there is additional evidence for dysregulation of either the hypothalamic-pituitary-adrenal axis or serotonin control of the hypothalamic-pituitary-adrenal axis in women with PMS, there is little evidence for luteal phase-specific serotonergic dysfunction. These findings, nonetheless, implicate the serotonin system as a modulating (not causal) factor in PMS.

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