Valproate and Neuroendocrine Changes in Relation to Women Treated for Epilepsy and Bipolar Disorder: A Review

Abstract

Valproic acid (2-n-propylpentanoic acid, VPA) is well-established as a mood-stabilizer for bipolar disorder, in addition to its application as a treatment in neurological disorders such as epilepsy, migraine headaches, and chronic neuropathic pain. Its mechanisms of actions in any of the disorders have not yet been fully elucidated but currently include GABA-ergic inhibitory effects, the suppression of NMDA-mediated excitatory neurotransmission, and possibly effects on monoamines and cerebral glucose metabolism. Given the rising use of VPA by women of reproductive age for various conditions it is increasingly important to understand how VPA affects reproductive and metabolic function in women, yet a number of key issues regarding VPA use in women of reproductive age remain unclear. These include the question of whether VPA use is associated with the development of polycystic ovary syndrome (PCOS)-like features (such as elevated androgen concentrations and/or chronic anovulation). The metabolic effects of VPA use, particularly on insulin sensitivity and weight gain, are also important to understand. Lastly, questions of VPA use during pregnancy and lactation require continued attention. This article reviews the current understanding of VPA's mechanisms of action, effects on the reproductive and metabolic system, and teratogenic qualities, highlighting important future areas of study.

Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer

“…HDACI that is used to treat epilepsy and bipolar disorder (73) and has demonstrated potent antitumor effects against several tumor types including renal and pancreatic cancer (74,75). The antifungal agent TSA is another well-established HDACI also with potent antitumor activity (76)(77)(78).…”

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

“…For example, valproic acid is a HDAC inhibitor and one of the most widely prescribed anti-epileptic drugs for its anticonvulsant properties. Although its precise mechanism of action remains unclear it is thought to involve an increase of the neurotransmitter gamma-aminobutyric acid (GABA) [101]. HDAC inhibitors are also being studied as possible treatments for polyglutamine diseases like Huntington's disease [102].…”

Long-Term Effects of Valproic Acid on Reproductive Endocrine Functions in Turkish Women with Epilepsy

“…VPA is a broad-spectrum AED against epilepsy [17][18][19][20] . It is rapidly absorbed after oral administration, undergoes extensive biotransformation in the liver via mitochondrial glucuronidation and cytosolic oxidation; its half-life ranges from 4 to 16 h but may vary due to concomitant drugs [19,20] .…”

“…It is rapidly absorbed after oral administration, undergoes extensive biotransformation in the liver via mitochondrial glucuronidation and cytosolic oxidation; its half-life ranges from 4 to 16 h but may vary due to concomitant drugs [19,20] . VPA inhibits many hepatic enzymes and may lead to unexpected interactions with other drugs, but, on the other hand, it is beneficial for young women on hormonal contraceptives (HCs); VPA is not likely to lead to contraception failure.…”