Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

Bilo, Leonilda; R, Meo; Nappi, Carmine; Annunziato, Lucio; Striano, Salvatore; Colao, A.; Merola, B; Buscaino, G A

doi:10.1111/j.1528-1157.1988.tb03770.x

Cited by 148 publications

(98 citation statements)

References 65 publications

(60 reference statements)

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“…Alterations in gonadotropin-releasing hormone (GnRH) secretion may cause neurotransmitter dysfunction between the hypothalamus-pituitary and the ovaries, which maintains normally menstrual cyclicity (29).…”

Section: Discussionmentioning

confidence: 99%

Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

et al. 2004

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Summary:Purpose: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years.Methods: Sixty-six female patients with epilepsy, their mean ages 13.47 ± 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group.Results: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzymeinducing AEDs (χ 2 = 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS.Conclusions: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder. Key Words: Epilepsy-FemaleAndrogenic hormones-PCOS-Endocrine functions.Reproductive and endocrine functions are of major concerns for clinicians who treat patients with epilepsy. An increased frequency of reproductive endocrine disorders has been reported in women with epilepsy (1). Considerable data pertaining to changes in the hormonal milieu of women with epilepsy and suggest that these individuals are more likely to have derangements of the menstrual cycles and polycystic ovary syndrome (PCOS) (2).A possible role of the seizure disorder or, alternatively, of the use of antiepileptic drugs (AEDs) has been sug-

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Section: Discussionmentioning

confidence: 99%

Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

et al. 2004

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“…Increased rates of reproductive and endocrine disorders have been documented in women with epilepsy for both primarily generalized (2), and partial epilepsies (3). Valproate (VPA) has been implicated in the development of polycystic ovarian disease and hyperandrogenism in women with epilepsy (4).…”

Section: Discussionmentioning

confidence: 99%

Male Infertility: Possible Association with Valproate Exposure

Yerby

McCoy

1999

Epilepsia

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Summary: Purpose: To describe a potential association between male infertility and valproate (VPA) exposure. VPA has been implicated in the development of polycystic ovarian disease and subsequent menstrual and infertility problems in women with epilepsy. Infertility has been well described in population-based studies of persons with epilepsy. The low marital rates for men with epilepsy have previously been thought to play a major contributing role.Methods: We report a case of a 32-year-old man whose wife and he were able to bear a child before the development of his epilepsy. With VPA monotherapy, the family were unable to conceive despite 4 years of unprotected intercourse. An infertility evaluation of the man revealed a very low sperm count of <50,00O/ml, no motile sperm, I6 million, 50% motility, 78% viability, and 72% with abnormal structure.Conclusions: One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of VPA on spermatic structure and function. Key Words: Valproate-Infertility-Epilepsy .It has been established that people with epilepsy, particularly women, have significantly lower fertility rates than persons without this disorder (1). Increased rates of reproductive and endocrine disorders have been documented in women with epilepsy for both primarily generalized (2), and partial epilepsies (3). Valproate (VPA) has been implicated in the development of polycystic ovarian disease and hyperandrogenism in women with epilepsy (4). Social and biologic influences affecting fertility in both men and women with epilepsy were studied by Schupf and Ottman (3, but relatively little attention has been paid to the issues of infertility in men with epilepsy. Chen et al. (6) studied the in vitro effect of antiepileptic drugs (AEDs) on human spermatic motility. They demonstrated marked inhibition of motility with exposure to phenytoin (PHT), carbamazepine (CBZ), and VPA. We report a case of a man with partial epilepsy whose infertility appeared to be associated with VPA exposure.

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“…Die häufigste reproduktive endokrine Störung bei Frauen mit Epilepsie als auch in der Allgemeinbevölkerung ist das polyzystische Ovarialsyndrom (PCOS) [2,15,17].…”

Section: Polyzystisches Ovarialsyndrom (Pcos)unclassified

Hormon- und Sexualstörungen bei Epilepsie

Luef

2018

Z. Epileptol.

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Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

Cited by 148 publications

References 65 publications

Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

Male Infertility: Possible Association with Valproate Exposure

Hormon- und Sexualstörungen bei Epilepsie

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