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).
Similar content being viewed by others
References
Isojarvi J., Laatikainen T., Pakarinen A., Juntenen K., Myllyla V. Polycystic ovarties and hyperandrogenism in women taking valproate for epilepsy. New Engl. J. Med. 329: 1383, 1993.
Loscher W., Siemes H. Valproic acid increases aminobutyric acid in CSF of epileptic children. Lancet 2: 225, 1984.
Waldstreicher J., Santoro N., Hall J., Filicori M., Crowley W. Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: an indirect evidence for partial gonadotroph desensitization. J. Clin. Endocrinol. Metab. 66: 165, 1988.
Zumoff B., Freeman R., Coupey S. et al. A chronobiologic abnormality in luteinizing hormone secretion in teenage girls with polycystic ovarian syndrome. N. Engl. J. Med. 309: 1206, 1983.
Graf M.A., Bielfeld P., Distler W., Weiers C., Kuhn-Velten W.N. Pulsatile luteinizing hormone secretion pattern in hyperandrogenemic women. Fertill. Steril. 59(4): 761, 1993.
Baien A.H. Hypersecrtion of luteinizing hormone and polycystic ovarian syndrome. Human. Reprod. 8(Suppl. 2): 123, 1993.
Hall J.E., Taylor A.E., Martin K.A., Crowley W.F. Jr. New approaches to the study of the neuroendocrine abnormalities of women with the polycystic ovarian syndrome. Ann. N. Y. Acad. Sci 687: 182, 1993.
Hales T., Sanderson M., Charles A. GABA has excitatory actions on GnRH-secreting immortalized hypothalamic (GT1-7) neurons. Neuroendocrinology 59: 297, 1994.
Jennes L, Strumpf W., Tappaz M. Anatomical relationships of dopaminergic and GABA-ergic systems with the GnRH systems in the septo-hypothalamic area. Exp. Brain. Res. 50: 91, 1983.
Lamberts Y., Vijayan E., Greefin M., Mansky T., Wuttke W. Involvement of preoptic anterior hypothalamic GABA neurons in the regulation of pituitary LH and prolactin release. Exp. Brain. Res. 52: 356, 1983.
Mansky T., Mesters-Ventura P., Wuttke W. Involvement of GABA in the feedback action of estradiol on gonadotropin and prolactin release:hypothalamic GABA and catecholamine turnover rates. Brain. Res. 231: 353, 1982.
Fuchs E., Mansky T., Stock K., Vijayan E., Wuttke W. Involvement of catecholamines and glutamate in GABA-ergic mechanism regularoty to luteinizing hormone and prolactin secretion. Neuroendocrinology 38: 484, 1984.
Abeal L., Agricola C., Carriera P., Cabezas-Cerato J. Influence of sodium valproate on late follicular phase pulsatile LH secretion in normal women. Clin. Endocrinol. (Oxf.) 35: 477, 1991.
Margaf J., Dreifuss F. Amenorrhoea following initiation of therapy with valproic acid. Neurology 31 (Suppl. 159) abstract, 1981.
Elias A., Szekeres A., Stone S., Valenta L. A presumptive role fro gamma-aminobutyric acid in the regulation of gonadotropin secretion in man. Am. J. Obstet. Gynecol. 144: 72, 1982.
Melis G., Mais V., Paoletti A., Maffei S., Antinori D., Fioretti P. GABA system. In: Adashi E., Mancuso M. (Eds.) Major Advances in Human Female Reproduction, vol. 73. Raven Press, New York, 1990, p. 251.
Herzog A.G. A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy. Neurology 43(10): 1907, 1993.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Popovic, V., Spremovic, S. The effect of sodium valproate on luteinizing hormone secretion in women with polycystic ovary disease. J Endocrinol Invest 18, 104–108 (1995). https://doi.org/10.1007/BF03349709
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03349709