Polycystic ovary syndrome in women using valproate: a review.
ABSTRACT Valproate (VPA) is a highly effective drug successfully employed in several neuropsychiatric diseases. In the last 15 years, an increased prevalence of polycystic ovary syndrome (PCOS) associated with VPA use has been reported in both women with epilepsy and women with bipolar disorders. However, data on this subject are contrasting and it is possible that different factors might play a role in the development of PCOS in these patients. The risk of developing PCOS during VPA treatment seems to be higher in women with epilepsy than in women with bipolar disorders, and this might be due to an underlying neuroendocrine dysfunction related to the seizure disorder. Gynecologists must be aware of the possibility that PCOS in these populations of patients might be related to VPA use, and a careful multi-specialist approach is required for evaluating the risks and benefits of this treatment in the presence of features of PCOS.
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ABSTRACT: We performed this study to evaluate the long-term efficacy and tolerability of ethosuximide (ESX), valproic acid (VPA), and lamotrigine (LTG) as initial monotherapies for patients with newly diagnosed childhood absence epilepsy. We retrospectively reviewed the medical records of 128 patients (45 boys and 83 girls) diagnosed with childhood absence epilepsy at the Seoul National University Hospital. The diagnosis was based on the criteria proposed by Panayiotopoulos in 2005. We measured the seizure-free rate and the retention rate observed during 2 years of treatment. Follow-up electroencephalography (EEG), any reported adverse events, and reasons for antiepileptic drug (AED) discontinuation were reviewed. The seizure-free rate of ESX (84%) was significantly higher than that of VPA (62%) and LTG (53%) at 3 months. The seizure-free rate of ESX (90%) was significantly higher than that of LTG (63%) at 6 months. After 9 months, there was no significant difference in seizure-free rate among the three groups. There were no significant differences among the three groups in terms of normalization of EEG at 12 months (ESX, 77%; VPA, 83%; and LTG, 64%), retention rate throughout the whole treatment period, and adverse-event rates (ESX, 25%; VPA, 29%; and LTG, 14%). This study suggests that ESX, VPA, and LTG are equally effective in the long-term treatment of newly diagnosed CAE patients. However, the onset of efficacy was faster for ESX compared with VPA or LTG. Efficacy, tolerability, and adverse event profiles should be carefully considered when selecting AEDs to treat individual patients with CAE.Brain & development 09/2011; 34(5):344-8. DOI:10.1016/j.braindev.2011.08.007 · 1.54 Impact Factor
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ABSTRACT: Lennox-Gastaut syndrome (LGS) is an intractable childhood-onset epileptic encephalopathy. Seizure freedom is rare in LGS. One of the hallmarks of LGS is medical intractability, with generally poor response to antiepileptic drugs (AEDs). Nevertheless, several treatment options are available that can mitigate the severity of seizures and curtail their frequency. New AEDs have been validated in randomized, controlled trials for the treatment of seizures in LGS. In some cases, nonpharmacologic options may be effective, although more data are needed to confirm efficacy outcomes. Comprehensive patient assessments are critical to achieve an optimal AED treatment regimen and minimize the potential for adverse effects.Epilepsia 08/2011; 52 Suppl 5:10-20. DOI:10.1111/j.1528-1167.2011.03178.x · 4.58 Impact Factor
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ABSTRACT: Several reports suggest putative interactions between valproic acid (VPA) treatment and the hypothalamus-pituitary-adrenal axis. Given that VPA alters mitochondrial functions, an action of this drug on a mitochondrial process such as steroid synthesis in adrenal cells should be expected. In order to disclose a putative action of VPA on the adrenocortical cell itself we evaluated VPA effects on regulatory steps of the acute stimulation of steroidogenesis in Y1 adrenocortical cells. This study demonstrates that VPA increases progesterone production in non-stimulated cells without inducing the levels of Steroidogenic Acute Regulatory (StAR) protein, which facilitates cholesterol transport. This result suggests that VPA increases mitochondrial cholesterol transport through a StAR-independent mechanism and is further supported by the fact that in isolated mitochondria VPA stimulates exogenous cholesterol metabolization to progesterone. VPA also reduces the cAMP-mediated increase of the StAR protein, mRNA levels, promoter activity and progesterone production. In summary, the present data show that VPA can alter steroid production in adrenal cells by a complex mechanism that mainly involves an action on cholesterol access to the inner mitochondrial membrane. The VPA-mediated increase of basal steroidogenesis could be linked to the increase of basal cortisolemia described in patients under VPA treatment.Toxicology in Vitro 02/2011; 25(1):7-12. DOI:10.1016/j.tiv.2010.08.006 · 3.21 Impact Factor