Antiepileptic drugs and puberty

Nalin, A; Galli, Vanna; Ciccarone, Vanna; Grandi, F.; Baraldi, Enrica; Carani, Cesare

doi:10.1016/s0387-7604(88)80029-9

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…This result was contrary to the suggested effect of epilepsy per se or hormonal disturbances on the hypothalamic-pituitary axis (21). However, an accelerated pubertal maturation also was reported by Nalin et al (22), who found that the onset of stage II puberty was significantly earlier in female treated patients than in healthy controls. Conversely, Rättyä et al (23) and Genton et al (2) reported that AEDs do not seem to have any adverse effects on sexual maturation in girls with epilepsy.…”

Section: Discussioncontrasting

confidence: 70%

“…VPA seems to inhibit the conversion of testosterone to estradiol, and this may act locally in the ovary to block ovulation or may accomplish this through negative feedback on follicle-stimulating hormone (FSH) secretion (22).…”

Section: Discussionmentioning

confidence: 99%

“…However, patients taking VPA had also menstrual disorders. VPA seems to inhibit the conversion of testosterone to estradiol, and this may act locally in the ovary to block ovulation or may accomplish this through negative feedback on follicle-stimulating hormone (FSH) secretion (22). Furthermore, it was previously suggested that reproductive disorders could be attributed to epilepsy itself rather than to AEDs.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2004

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“…Hormone changes during puberty can induce or exacerbate epilepsy [Klein et al, 2003] and estrogens play a part in facilitating seizures, while progesterone has an antiepileptic effect [Herzog et al, 1997; Herzog, 1999]. Ictal and interictal paroxysmal discharges can also induce sex hormone changes, influencing the functionality of the hypothalamus–pituitary axis [Herzog et al, 2003], but there is no evidence of epilepsy affecting the age of menarche [Herzog, 2006], despite a few case series of epileptic female patients reaching puberty early by comparison with the healthy population [Nalin et al, 1988; El‐Khayat et al, 2004]. A recent epidemiological study comparing age at menarche in a large sample of girls with epilepsy whose seizures developed in infancy versus those whose seizures developed in adolescence and adulthood also seems to rule out any correlation between the age of onset of epilepsy and any anticipation of pubertal development [Svalheim et al, 2006].…”

Section: Discussionmentioning

confidence: 99%

A CDKL5 mutated child with precocious puberty

Saletti

Canafoglia

Cambiaso

et al. 2009

American J of Med Genetics Pt A

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To date, 43 patients have been described with mutations in or involving the CDKL5 gene. The typical phenotype includes early-onset, often intractable epileptic seizures and severe mental retardation with very limited progress in psychomotor development. Most patients also show impaired social interaction with avoidance of eye-to-eye contact, and some clinical features reminiscent of Rett syndrome (RTT), including stereotypic hand movements, lack of purposeful hand use, acquired microcephaly, and generalized hypotonia. We report on the case of a 5-year-old girl with a de novo CDKL5 gene mutation who developed early puberty, which has not been described before.

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“…Reproductive and sexual dysfunction in men with epilepsy has been attributed to androgen deficiency (Herzog 1991, Mattson & Cramer 1985. Antiepileptic drugs may alter the release and action of different hormones (Timiras & Hill 1980;Fichsel 1981;Trimble & Corbett 1983;Davies-Jones 1987& 1988Eadie 1987;Nalin et al 1988). Gonadal steroid function is altered in some epileptic patients treated with antiepileptic medication which may also contribute to sexual dysfunction (Isojarvi et al 1990;Cramer & Jones 1991).…”

mentioning

confidence: 99%

Effects of Long‐Term Antiepileptic Therapy on the Catabolism of Testosterone

Brunet

Rodamilans

et al. 1995

Pharmacology & Toxicology

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The serum levels of testosterone, sex hormone binding globulin, and free testosterone index were measured in 51 epileptic men (age 18-45) in order to assess the possible effects of antiepileptic drugs on sexual dysfunction. An analytical gas chromatography-mass spectrometry method was developed to assess the urinary excretion of testosterone, epitestosterone, androsterone, etiocholanolone, 11-OH androsterone and 11-OH etiocholanolone and to evaluate if the catabolism of testosterone had been increased. Twenty normal healthy males of similar age, 18-45 years, served as control group. Patients receiving polytherapy (n = 34) or monotherapy with carbamazepine (n = 8) or phenytoin (n = 9) showed higher levels of sex hormone binding globulin and testosterone, and lower levels of free testosterone than did the controls (P < 0.03). Urinary excretion of the metabolites androsterone and 11-OH androsterone was significantly reduced (P < 0.02) in the polytherapy group, while the monotherapy group showed only significant differences (P < 0.02) in the elimination of 11-OH androsterone. Our results suggest that an induction of the hepatic synthesis of sex hormone binding globulin may be the mechanism by which the antiepileptic drugs lower the levels of free testosterone in serum. However, the reduced excretion of androsterone and the normal levels of etiocholanolone show that the antiepileptic drugs do not produce an increase in the main catabolism pathway of testosterone.

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Antiepileptic drugs and puberty

Cited by 5 publications

References 6 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

A CDKL5 mutated child with precocious puberty

Effects of Long‐Term Antiepileptic Therapy on the Catabolism of Testosterone

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