Characterization of Reproductive Endocrine Disorders in Women with Epilepsy

Abstract

An increased frequency of reproductive endocrine disorders has been reported in women with epilepsy. A possible role of the seizure disorder or, alternatively, of the use of antiepileptic drugs (AEDs) has been suggested as the pathogenic mechanism. The aim of the present study was to assess the frequency of reproductive endocrine disorders in a series of women with epilepsy, examining the possible relationships of these disturbances with different epilepsy syndromes and AED treatment. Fifty epileptic women, all of reproductive age and none pubertal, pregnant, or lactating, were submitted to clinical endocrinological evaluation, hormonal assessment, and ovarian ultrasonography. Subjects with abnormal findings in this preliminary study underwent additional evaluations. Reproductive endocrine disorders were diagnosed in 16 (32%), consisting of polycystic ovary syndrome in 13, hypothalamic amenorrhea in 2, and luteal phase deficiency in 1. There was no significant association of these disturbances with epilepsy type or AED treatment. Patients with reproductive endocrine disorders often showed delayed ovulation with shortened luteal phase. The results of this study suggest that the prevalence of disordered ovulation, in particular polycystic ovary syndrome, is increased in epilepsy, independent of antiepileptic medications or type of seizure disorder.

The Relationship Between Polycystic Ovary Syndrome and Antiepileptic Drugs

“…Some evidence suggests that isolated symptoms of PCOS are more frequent in women with epilepsy and bipolar disorder than in the general population. 9,10,[62][63][64] In addition, the effect of duration of exposure to AEDs on the development of reproductive disorders has not been definitively established. Only a subset of the studies reviewed here reported the age of study subjects, which fell between 20 and 40 years, or the duration of treatment, which varied widely even within single studies.…”

“…56 In general, it has been reported that PCOS occurs in 10.5% to 26% of women with epilepsy. 9,10 Some authors have suggested that epilepsy may play an intrinsic role in the development of PCOS. 55,57 Epileptic discharges from the amygdala to the hippocampus may affect the secretion of gonadotropin releasing hormone (GnRH).…”

“…1). 9,10 Clinical Characteristics Hyperandrogenism and anovulation are the key features of PCOS as defined by the NIH. 5 Hyperandrogenism may appear clinically as hirsutism, acne, or alopecia.…”

Neuroendocrine Hormonal Conditions in Epilepsy

“…The presence of increased LH pulse frequency in untreated or drug-free epileptic women with regular menstrual cycles supports the notion that epilepsy itself may contribute for reproductive abnormalities. 104 The different patterns of reproductive endocrine abnormalities related to different seizure types (idiopathic vs. localization-related epilepsy) further support that epilepsy itself is responsible for these abnormalities. Hyperandrogenemia, PCOs, and PCOS are more frequent in women with idiopathic generalized epilepsy than in localization-related epilepsy.…”

Neurogonadale Interaktionen bei Frauen mit Epilepsie

“…Bei Frauen mit Epilepsie ohne AED-Therapie wird eine erhöhte LH-Pulsfrequenz beobachtet [1]. Zyklusstörungen traten allerdings bei den in dieser Studie untersuchten Patientinnen trotz der erhöhten LH-Pulse nicht gehäuft auf, obwohl diese insgesamt bei Frauen mit Epilepsie überreprä-sentiert sind [2], und zwar unabhängig von einer AED-Therapie. Möglicherwei-se handelt es sich bei der hypothalamischen Dysregulation zunächst um subklinische Veränderungen, die einer Manifestation endokriner Störungen unter zusätzlichen Belastungsmomenten vorangehen und diese begünstigen.…”