INFLUENCE OF SODIUM VALPROATE ON MEDIUM-LATE LUTEAL-PHASE PULSATILE LH-SECRETION IN NORMAL WOMEN

OBJECTIVE It is not known whether gamma-aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. in this work we studied the effect of sodium valproate on pulsatile LH secretion in medium-late luteal phase of normal women. DESIGN Six normal young women were studied over an 8-hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations. MEASUREMENTS In each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non-parametric statistic. The statistical significance of differences between parameters was estimated using the Mann-Whitney test and Wilcoxon signed rank test. RESULTS There were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate. CONCLUSIONS Activation of the GABAergic system with sodium valproate had no biologically significant effect on the mid-late luteal phase pulsatile LH secretion in normal women.