Background Reproductive endocrine disorders are more commonamong women with epilepsy than among normal women. These disordershave been attributed to epilepsy itself, but could be relatedto antiepileptic-drug therapy.
Methods We studied 238 women with epilepsy who were seen regularlyat the Outpatient Department of the University Hospital, Oulu,Finland. Their mean age was 33 years (range, 18 to 45), andthe mean duration of therapy was 9 years (range, 0 to 31). Twenty-nine(12 percent) were treated with valproate, 120 (50 percent) withcarbamazepine, 12 (5 percent) with valproate and carbamazepine,and 62 (26 percent) with other medications; 15 (6 percent) wereuntreated. Vaginal ultrasonography was performed to determineovarian size, and serum sex-hormone concentrations were measuredin 41 women with epilepsy and menstrual disturbances, 57 womenwith epilepsy and regular menstrual cycles, and 51 normal women.
Results Menstrual disturbances were present in 13 of the womenreceiving valproate alone (45 percent), 3 of the women receivingvalproate in combination with carbamazepine (25 percent), 23of the women receiving carbamazepine (19 percent), and 8 ofthose receiving other medications (13 percent). Forty-threepercent of the women receiving valproate had polycystic ovaries,and 17 percent had elevated serum testosterone concentrationswithout polycystic ovaries; 50 percent of the women receivingvalproate and carbamazepine had polycystic ovaries, and 38 percenthad elevated serum testosterone concentrations without polycysticovaries. Eighty percent of the women treated with valproatebefore the age of 20 years had polycystic ovaries or hyperandrogenism.
Conclusions Menstrual disturbances, polycystic ovaries, andhyperandrogenism are often encountered in women taking valproatefor epilepsy.
Source Information
From the Departments of Neurology (J.I.T.I., V.V.M.), Obstetrics and Gynecology (T.J.L., K.T.S.J.), and Clinical Chemistry (A.J.P.), University of Oulu, Oulu, Finland.
Address reprint requests to Dr. Isojarvi at the Department of Neurology, University of Oulu, SF-90220 Oulu, Finland.
French, J. A., Pedley, T. A.
(2008). Initial Management of Epilepsy. NEJM
359: 166-176
[Full Text]
Artama, M., Isojarvi, J.I.T., Auvinen, A.
(2006). Antiepileptic drug use and birth rate in patients with epilepsy--a population-based cohort study in Finland. Hum Reprod
21: 2290-2295
[Abstract][Full Text]
Jackson, M.
(2006). Epilepsy in women: a practical guide to management. PN
6: 166-179
[Full Text]
Veldhuis, J. D., Roemmich, J. N., Richmond, E. J., Bowers, C. Y.
(2006). Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition. Endocr. Rev.
27: 101-140
[Abstract][Full Text]
Herzog, A. G.
(2006). Menstrual disorders in women with epilepsy. Neurology
66: S23-S28
[Abstract][Full Text]
Mujgan Sonmez, F., Demir, E., Orem, A., Yildirmis, S., Orhan, F., Aslan, A., Topbas, M.
(2006). Effect of Antiepileptic Drugs on Plasma Lipids, Lipoprotein (a), and Liver Enzymes. J Child Neurol
21: 70-74
[Abstract]
O'Brien, M D, Gilmour-White, S K
(2005). Management of epilepsy in women. Postgrad. Med. J.
81: 278-285
[Abstract][Full Text]
Anderson, G. D.
(2004). Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology
63: S3-S8
[Abstract][Full Text]
Kaplan, P. W.
(2004). Reproductive health effects and teratogenicity of antiepileptic drugs. Neurology
63: S13-S23
[Abstract][Full Text]
Mikkonen, K., Vainionpaa, L. K., Pakarinen, A. J., Knip, M., Jarvela, I. Y., Tapanainen, J. S., Isojarvi, J. I.
(2004). Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology
62: 445-450
[Abstract][Full Text]
Nelson-DeGrave, V. L., Wickenheisser, J. K., Cockrell, J. E., Wood, J. R., Legro, R. S., Strauss, J. F. III, McAllister, J. M.
(2004). Valproate Potentiates Androgen Biosynthesis in Human Ovarian Theca Cells. Endocrinology
145: 799-808
[Abstract][Full Text]
Tatum, W. O. IV, Liporace, J., Benbadis, S. R., Kaplan, P. W.
(2004). Updates on the Treatment of Epilepsy in Women. Arch Intern Med
164: 137-145
[Abstract][Full Text]
Isojarvi, J. I. T.
(2003). Reproductive dysfunction in women with epilepsy. Neurology
61: S27-34
[Abstract][Full Text]
Graziani, G., Tentori, L., Portarena, I., Vergati, M., Navarra, P.
(2003). Valproic Acid Increases the Stimulatory Effect of Estrogens on Proliferation of Human Endometrial Adenocarcinoma Cells. Endocrinology
144: 2822-2828
[Abstract][Full Text]
Ferin, M., Morrell, M., Xiao, E., Kochan, L., Qian, F., Wright, T., Sauer, M.
(2003). Endocrine and Metabolic Responses to Long-Term Monotherapy with the Antiepileptic Drug Valproate in the Normally Cycling Rhesus Monkey. J. Clin. Endocrinol. Metab.
88: 2908-2915
[Abstract][Full Text]
Biton, V., Levisohn, P., Hoyler, S., Vuong, A., Hammer, A. E.
(2003). Lamotrigine Versus Valproate Monotherapy--Associated Weight Change in Adolescents With Epilepsy: Results From a Post Hoc Analysis of a Randomized, Double-Blind Clinical Trial. J Child Neurol
18: 133-139
[Abstract]
Hirschfeld, R. M.A., Bowden, C. L., Gitlin, M. J., Keck, P. E., Perlis, R. H., Suppes, T., Thase, M. E., Wagner, K. D.
(2003). Practice Guideline for the Treatment of Patients With Bipolar Disorder (Revision). Focus
1: 64-110
[Full Text]
Balen, A., Michelmore, K.
(2002). What is polycystic ovary syndrome?: Are national views important?. Hum Reprod
17: 2219-2227
[Abstract][Full Text]
Bauer, J, Isojarvi, J I T, Herzog, A G, Reuber, M, Polson, D, Tauboll, E, Genton, P, van der Ven, H, Roesing, B, Luef, G J, Galimberti, C A, van Parys, J, Flugel, D, Bergmann, A, Elger, C E
(2002). Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management. J. Neurol. Neurosurg. Psychiatry
73: 121-125
[Abstract][Full Text]
Verrotti, A., Basciani, F., De Simone, M., Trotta, D., Morgese, G., Chiarelli, F.
(2002). Insulin Resistance in Epileptic Girls Who Gain Weight After Therapy With Valproic Acid. J Child Neurol
17: 265-268
[Abstract]
Crumrine, P. K.
(2002). Antiepileptic Drug Selection in Pediatric Epilepsy. J Child Neurol
17: 2S2-2S8
[Abstract]
Sheth, R. D.
(2002). Adolescent Issues in Epilepsy. J Child Neurol
17: 2S23-2S27
[Abstract]
Joffe, H., Taylor, A. E., Hall, J. E.
(2001). EDITORIAL: Polycystic Ovarian Syndrome--Relationship to Epilepsy and Antiepileptic Drug Therapy. J. Clin. Endocrinol. Metab.
86: 2946-2949
[Full Text]
Bilo, L., Meo, R., Valentino, R., Di Carlo, C., Striano, S., Nappi, C.
(2001). Characterization of Reproductive Endocrine Disorders in Women with Epilepsy. J. Clin. Endocrinol. Metab.
86: 2950-2956
[Abstract][Full Text]
Biton, V., Mirza, W., Montouris, G., Vuong, A., Hammer, A.E., Barrett, P.S.
(2001). Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology
56: 172-177
[Abstract][Full Text]
Hattori, N., Fujiwara, H., Maeda, M., Fujii, S., Ueda, M.
(2000). Epoxide Hydrolase Affects Estrogen Production in the Human Ovary. Endocrinology
141: 3353-3365
[Abstract][Full Text]
Isojarvi, J. I. T., Tapanainen, J. S.
(2000). Valproate, Hyperandrogenism, and Polycystic Ovaries: A Report of 3 Cases. Arch Neurol
57: 1064-1068
[Abstract][Full Text]
Novak, G. P., Maytal, J., Alshansky, A., Eviatar, L., Sy-Kho, R., Siddique, Q.
(1999). Risk of Excessive Weight Gain in Epileptic Children Treated with Valproate. J Child Neurol
14: 490-495
[Abstract]
Appleton, R. E, Neville, B. G R
(1999). Teenagers with epilepsy. Arch. Dis. Child.
81: 76-79
[Full Text]
Devinsky, O.
(1999). Patients with Refractory Seizures. NEJM
340: 1565-1570
[Full Text]
Case, A. M., Reid, R. L.
(1998). Effects of the Menstrual Cycle on Medical Disorders. Arch Intern Med
158: 1405-1412
[Abstract][Full Text]
Löppönen, T., Saukkonen, A.-L., Serlo, W., Tapanainen, P., Ruokonen, A., Knip, M.
(1997). Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus. Arch. Dis. Child.
77: 32-37
[Abstract][Full Text]
(1993). VALPROATE IS LINKED TO POLYCYSTIC OVARIES AND HYPERANDROGENISM. JWatch General
1993: 6-6
[Full Text]
Previous
