Influence of Valproic Acid on the Gonadotropin‐Releasing Hormone Test in Puberty

Lundberg, Bo; Nergårdh, Arne; Ritzén, E. M.; Samuelsson, Kristin

doi:10.1111/j.1651-2227.1986.tb10291.x

Cited by 18 publications

(6 citation statements)

References 17 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, an AED effect cannot be ruled out as far as the blunted LH response to GnRH is concerned. In fact, a blunted LH response during VPA treatment is reported in epileptic males, menopausal women, and adolescents (Giroud et al, 1985;Lundberg et al, 1986). Conversely, in normal females of reproductive age, the LH response during the follicular phase seems unaffected by VPA administration (Elias et a!., 1982;Melis et al, 1986b).…”

Section: Time ( M I Dmentioning

confidence: 99%

Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

et al. 1988

View full text Add to dashboard Cite

It is known that women suffering from temporal lobe epilepsy may frequently present reproductive endocrine disorders (REDs). We hypothesized that a high occurrence of REDs could be found also in primary generalized epilepsy (PGE), and therefore investigated the hormonal and ovarian echographic profiles in 20 PGE female patients of reproductive age. Fourteen reported normal menstrual cycles, while 6 complained of longstanding menstrual irregularities. All but three patients were receiving antiepileptic drug (AED) therapy. In all subjects, the basal levels of gonadotropins, prolactin, and gonadal steroids were assayed. The response of luteinizing hormone (LH) to gonadotropin-releasing hormone was also investigated and ovarian ultrasonographic findings were evaluated. In five of six patients with menstrual problems (25% of the group), a well-defined RED was diagnosed (polycystic ovarian disease in three cases and hypothalamic ovarian failure in two). The 14 patients with normal menstrual cycles showed an elevation of mean basal follicle-stimulating hormone and prolactin, and a blunting of mean LH response. Our results suggest that a high occurrence of REDs may be found also in PGE. We hypothesize that a neurotransmitter dysfunction might be the common pathogenetic mechanism resulting in both REDs and PGE. The hormonal alterations observed in the patients with normal menstrual cycles seem to support our hypothesis. Previous data seem to rule out a possible AED effect accounting for the hormonal findings observed in our series. However, further studies are needed to confirm our preliminary results.

show abstract

Section: Time ( M I Dmentioning

confidence: 99%

Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

et al. 1988

View full text Add to dashboard Cite

show abstract

“…However, given that recently postpubescent girls have a high incidence of anovulation, it is possible that the relative immaturity of the HPG axis at this time period makes it more vulnerable to perturbation 45 . Preliminary reports suggest that initiation of valproate during puberty suppresses gonadotropin secretion, but does not influence pubertal development, 46 although case reports suggest that pubertal growth and maturation can be arrested 47 …”

Section: Valproate Use and Polycystic Ovarian Syndromementioning

confidence: 99%

Menstrual Cycle Dysfunction Associated with Neurologic and Psychiatric Disorders

Joffe

Hayes

2008

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Epilepsy, bipolar disorder, and migraines are common disorders that are often associated with disturbances in menstrual function in adolescent girls. Women with untreated epilepsy are more likely to have irregular menstrual cycles than are nonepileptic controls, indicating that the disease itself plays a role in the etiology of these reproductive abnormalities. In addition, many girls with these disorders require chronic maintenance treatment with agents that may perturb the hypothalamic-pituitary-ovarian axis. Valproate is a highly effective antiepileptic drug used widely to treat epilepsy, bipolar disorder, and migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder, appear particularly susceptible to developing PCOS features on valproate, perhaps on account of the relative immaturity of their hypothalamic-pituitary-ovarian axes. Antipsychotics are highly effective drugs used widely to treat adolescents with bipolar disorder, psychotic disorders, and behavioral disturbances. Some, but not all of the antipsychotic, induce hyperprolactinemia, which may result in oligo- or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia incurs significant risks for bone health in adolescent girls. Because of the potential reproductive health risks associated with use of specific antiepileptic drugs and selective antipsychotics, these agents are vital treatments for adolescents with severe illnesses. Use of these agents should be considered and weighed against the risk of using alternative agents, which have their own side effects, or not treating these serious neurologic and psychiatric disorders.

show abstract

“…Precocious puberty is often associated with epilepsy in children (8,9). Furthermore, treatment with sodium valproic acid, a GABA agonist-the mechanism of action has yet to be determined-delays the timing of puberty in children with seizure disorders (330,331) and in genetically epilepsy-prone mice (332). It is possible that the pubertal increase in gonadal steroids may sensitize neurocircuits involved in epileptic seizures, but it is also possible that there is a common mechanism of developmental deficiency, i.e., weakened GABA inhibition in the LHRH neuronal system resulting in precocious puberty and weakened GABAergic inhibition in the brain at the pubertal age resulting in epilepsy (333).…”

Section: G the Role Of Gaba In Sexual Differentiation In The Brainmentioning

confidence: 99%

Neurobiological Mechanisms of the Onset of Puberty in Primates*

2001

View full text Add to dashboard Cite

An increase in pulsatile release of LHRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in LHRH release is still unclear. In primates the LHRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state in the juvenile/prepubertal period. Neither gonadal steroid hormones nor the absence of facilitatory neuronal inputs to LHRH neurons is responsible for the low levels of LHRH release before the onset of puberty in primates. Recent studies suggest that during the prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of the hypothalamus this prepubertal inhibition is removed, allowing the adult pattern of pulsatile LHRH release. In fact, y-aminobutyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before the onset of puberty in female rhesus monkeys. In addition, it appears that the reduction in tonic GABA inhibition allows an increase in the release of glutamate as well as other neurotransmitters, which contributes to the increase in pubertal LHRH release. In this review, developmental changes in several neurotransmitter systems controlling pulsatile LHRH release are extensively reviewed.

show abstract

Influence of Valproic Acid on the Gonadotropin‐Releasing Hormone Test in Puberty

Cited by 18 publications

References 17 publications

Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

Reproductive Endocrine Disorders in Women with Primary Generalized Epilepsy

Menstrual Cycle Dysfunction Associated with Neurologic and Psychiatric Disorders

Neurobiological Mechanisms of the Onset of Puberty in Primates*

Contact Info

Product

Resources

About