The effect of sodium valproate on luteinizing hormone secretion in women with polycystic ovary disease

Abstract

The aim of this study was to examine whether modulation of the GABA-ergic system (with sodium valproate) affects gonadotropin secretory frequency and amplitude in women with polycystic ovarian syndrome (PCOS). Six women aged 25 +/- 2 years with diagnosed PCOS and six healthy women aged 26 +/- 2 years at day 7-11 of menstrual cycle were included in the study. Sodium valproate 1200 mg p.o./day (600 mg t.i.d.) was administered for five days in both groups. Efficacy of treatment was assessed in women with PCOS by measuring six hour LH pulsatility (every .10 min), and by GnRH tests before and after treatment. Basal serum steroids were assessed as well. Hormones were determined by radioimmunoassay and pulse detection was carried out by the program PULSAR. The administration of valproate did not change basal serum LH concentration (9.1 +/- 0.6 vs 9.0 +/- 0.8 IU/L p > 0.05) nor LH pulse frequency (7.3 +/- 0.5 vs 6.3 +/- 0.5 p > 0.05) or the LH pulse amplitude (3.0 +/- 0.5 vs 3.5 +/- 0.4 p > 0.05). LH response to GnRH (mean peak 43.6 +/- 5.2 vs 44.1 +/- 6.0 IU/L p > 0.05) did not change either. Valproate did not affect the LH secretory activity in women with PCOS. There was no change in FSH, and prolactin secretion. In five patients with PCOS valproate caused further increase in serum testosterone level but this did not reach significance in the group as a whole (5.6 +/- 1.0 vs 9.1 +/- 2.0 nmol/L p > 0.05).

Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women

“…This low level of research activity has been due partly to blood samples, and partly to the lack of a broad group of safe, specific drugs allowing external control of this interaction. We have reported previously that VPA-induced alteration of the GABAergic system has no significant effect on pulsatile LH secretion by normal women during the late follicular phase (22) and mid-late luteal phase (23) (and therefore no effect on mean serum LH concentrations during these periods), a finding in keeping with the results of other researchers (41)(42)(43). The results on ovariectomized women now reported appear to confirm that, in this respect as in others, the neurotransmitter-mediated mechanisms controlling the hypothalamo-pituitary axis in humans differ from those operating in rats.…”

“…In particular, hardly any work has been done on the possible relationship ofthe GABAergic system to the pulsatility of LH secretion (22,23,42). This low level of research activity has been due partly to blood samples, and partly to the lack of a broad group of safe, specific drugs allowing external control of this interaction.…”

Valproate and Neuroendocrine Changes in Relation to Women Treated for Epilepsy and Bipolar Disorder: A Review

“…Early studies in normal (short-term VPA use) and epileptic (long-term VPA use) populations did not indicate an effect of VPA on prolactin [150,[167][168][169]. In 1988, Bilo et al found increased concentrations of prolactin in a female epileptic population but could not definitively relate it to AED use, or VPA use in particular [139].…”

“…Popovic et al studied endocrine status in a healthy population administered VPA over the course of two or five days and did not find any changes in FSH or LH secretion [150]. In a follow-up study, however, the authors found that postmenopausal women not on hormone replacement therapy and healthy reproductive-aged women in their mid-luteal phase both exhibited LH suppression in acute response to VPA administration, whereas postmenopausal women receiving hormone replacement therapy showed no acute change in LH or FSH.…”

“…Indeed, cross-sectional study results in epileptic populations tend to converge in finding that VPA use is associated with elevated serum androgen levels-frequently measured as total serum testosterone, free testosterone, and androstenedione [86,87,89,115,130,132,143,[149][150][151][152][153][154][155][156]. However, at least one study did not find a significant difference in androgens between medication groups [157].…”