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From the Department of Pediatrics (Drs. Mikkonen and Vainionpää), Clinical Chemistry (Dr. Pakarinen), Obstetrics and Gynecology (Drs. Järvelä and Tapanainen), and Neurology (Dr. Isojärvi), University of Oulu, and Hospital for Children and Adolescents (Dr. Knip), University of Helsinki, Finland.
Address correspondence and reprint requests to Dr. K. Mikkonen, PO Box 5000, FIN-90014 University of Oulu, Oulu, Finland; e-mail: kirsi.ruotsalainen{at}oulu.fi
Objective: To evaluate the outcome of epilepsy and later reproductive endocrine health in girls who had epilepsy during puberty, using a population-based controlled study.
Methods: Sixty-nine patients (88%) and 51 control subjects (94%) of previously identified cohorts of 78 girls with epilepsy and 54 healthy control girls participated in this study (initial age 8 to 18.5 years, at follow-up 12.5 to 25.8 years). Thirty-five of the patients were initially taking valproate (VPA), 17 carbamazepine, and 17 oxcarbazepine as monotherapy. Most of the patients (61%) were off medication. All the subjects were examined clinically, the medical and menstrual histories were obtained, ovarian ultrasonography was examined, and serum reproductive hormone concentrations were analyzed.
Results: There were no significant differences in laboratory or clinical findings between the patients off medication and the control subjects. Postpubertal patients on medication had higher serum testosterone (1.9 nmol/L, SD 0.7 nmol/L) and androstenedione (18.8 nmol/L, SD 15.2 nmol/L) levels than patients off medication (1.4 nmol/L, SD 0.5 nmol/L, and 9.5 nmol/L, SD 2.6 nmol/L) or control subjects (1.4 nmol/L, SD 0.5 nmol/L, and 10.2 nmol/L, SD 3.2 nmol/L) (all comparisons p < 0.02). All patients still on VPA had elevated serum androstenedione levels. Polycystic ovary syndrome was more common in patients on medication (38%; in 63% on VPA, in 25% on other medication) than in patients off medication (6%) or in controls (11%) (p = 0.005).
Conclusions: Epilepsy during pubertal maturation does not affect reproductive endocrine health in female subjects who discontinue the medication before adulthood. However, an increased prevalence of endocrine disorders is detected if the patients remain on antiepileptic drugs, especially VPA, until adulthood.
Received June 19, 2003. Accepted in final form October 17, 2003.
Dr. Isojärvi has received honoraria from Glaxo Wellcome/GlaxoSmithKline, Novartis, and Sanofi Winthrop during the last 5 years. He has also received financial support for research from Glaxo Wellcome/GlaxoSmithKline and Novartis. He has been an employee of Orion Pharma and GlaxoSmithKline.
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