Neuroendocrine correlates of premenstrual syndrome: changes in the pulsatile pattern of plasma LH

Some studies suggest that patients suffering from premenstrual syndrome (PMS) may be affected by an endogenous opioid dysfunction. Since opioids are the main modulators of the pulsatile LH secretion, we evaluated plasma LH pulsatility in 13 patients with PMS (aged 33.1 yr) and in six asymptomatic control volunteers (aged 31.5 yr), in the late luteal phase (-7, -5 days before their next menses). The patients were prospectively evaluated for two menstrual cycles with the Menstrual Distress Questionnaire; the main symptoms which worsened during the premenstrual period were mood swings and water retention. The pulsatility of plasma LH secretion was studied by collecting blood samples every 10 min for 12 hr, starting at 0800h. The presence of LH pulses was estimated using the program DETECT on the raw data. This program also allows the computation of the instantaneous secretory rate (ISR). Ovulation was ascertained in all the controls and in nine PMS patients by means of urinary LH assay and luteal progesterone (P) determination. The remaining four patients did not ovulate. Both the ovulatory and the anovulatory PMS patients had an increased number of LH pulses/12 hr (10.3 +/- 2.4 and 11.5 +/- 4.4, mean +/- SD, respectively) in comparison with the controls (7.0 +/- 1.3 pulses, p less than 0.01), together with a reduced amplitude and duration. Similar findings were obtained with the ISR computation. Plasma P levels were similar in both the ovulatory patients and controls. The increased frequency and reduced amplitude of LH pulses in the PMS patients most likely reflect a dysfunction of hypothalamic Gn-RH release, possibly linked to a reduction of opioid inhibition.