Abstract
Previous observations have indicated that reproductive endocrine disorders are common among patients with
epilepsy. Valproate (VPA) treatment is associated with hyperandrogenism, polycystic ovaries, and obesity in women.
Carbamazepine (CBZ) may also induce endocrine disorders, while the hormonal effects of oxcarbazepine (OXC) are
poorly known. The aim of this study was to elucidate the effects of antiepileptic drugs on reproductive hormones,
linear growth and pubertal maturation in patients with epilepsy.
Altogether 223 patients taking VPA, CBZ, or OXC monotherapy for epilepsy and 103 healthy age- and sex-matched
volunteers participated in the study. Seventy-eight girls and 90 men with epilepsy participated in the
cross-sectional parts of the study. Thirty-nine adult patients with newly diagnosed epilepsy participated in
a 3-month longitudinal study and VPA was replaced with lamotrigine (LTG) in 16 women with VPA-related endocrine
disorders in a 1-year longitudinal study. The girls were between 8-18 years, the women 17-41 years and the men
17-51 years of age.
None of the antiepileptic drugs studied significantly influenced linear growth or pubertal development in girls
with epilepsy, but hyperandrogenemia, increased number of ovarian follicles, and weight gain were observed in
prepubertal, pubertal and postpubertal girls taking VPA for epilepsy. Increased serum testosterone levels were
observed in half of the women after the first 3 months of VPA medication, and high serum concentrations of
androgens were common (prevalence 57 %, p < 0.001) in men taking long-term VPA treatment. The women with
VPA-related hyperandrogenism and polycystic ovaries were also found to present other features of insulin
resistance (i.e. hyperinsulinemia, centripetal obesity, and an unfavorable serum lipid profile). Reproductive
endocrine disorders associated with VPA treatment in women began to normalize after VPA was replaced by LTG. CBZ
reduced the bioactivity of androgens, whereas OXC did not have similar effects. Serum concentrations of sex
hormone-binding globulin (SHBG) were increased and dehydroepiandrosterone sulfate decreased already during the
first months of CBZ treatment. Serum hormone levels were normal in patients with low OXC doses (< 900 mg/d),
but serum concentrations of testosterone, gonadotropins and SHBG were high in men with a daily OXC dose ≥ 900 mg.
The adverse reproductive endocrine effects of antiepileptic drugs should be considered at the beginning of and
during antiepileptic medication.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5529-1 |
| Date | 12 January 2000 |
| Creators | Rättyä, J. (Johanna) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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