Sodium Valproate-Induced Menstrual Disturbance in Young Women

Jones, T. Hugh

doi:10.1159/000181878

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…The net result is a lower amount of free, biologically active hormone in the circulation, which, in turn, would alter the hormonal feedback regulation of pituitary gonadotropins and hence, gonadal function (14,15). Other drugs, including sodium valproate, the benzodiazepines, and vigabatrin (VGB), affect circulating steroid hormone concentrations more directly by decreasing GnRH release through enhanced y-aminobutyric acid (GABA)ergic input to the GnRH neurons (16,17). These problems can be avoided by using animal models of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…Seventy-nine percent (33 of 42) kindled females exhibiting PVC had polyfollicular ovaries (data pooled for both P,-treated and untreated rats). In the kindled females that did not receive P,, the mean number of large peripheral follicles per ovary was 15.7 1.7 (range, [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Corpora lutea were not found in the ovaries of these females.…”

Section: Effect Of Kindling On Reproductive Tissues and Serum Hormonesmentioning

confidence: 99%

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Limbic Seizures Alter Reproductive Function in the Female Rat

Edwards

Burnham

et al. 1999

Epilepsia

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Summary:Purpose: Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction.Methods: Kindling electrodes were implanted in the basolatera1 amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears.Results: Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P, administration restored cyclicity in all five shamkindled controls that had spontaneously stopped cycling. P, treatment to kindled females in PVC resulted in a different endocrine profile than that in non-P4-treated, kindled rats in PVC. P4-treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers.Conclusions: Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Kindling On Reproductive Tissues and Serum Hormonesmentioning

confidence: 99%

Limbic Seizures Alter Reproductive Function in the Female Rat

Edwards

Burnham

et al. 1999

Epilepsia

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“…In 1991, however, a case report of two young girls who developed menstrual cycle irregularities while on VPA [142] initiated an investigation into VPA's effects on reproductive function that continues today.…”

Section: Menstrual Abnormalities and Anovulationmentioning

confidence: 99%

“…In an animal study using Wistar rats given 90 days of low and high dose VPA exposure, the researchers found that while FSH was unaltered, LH was lower in the rats administered the low dose of VPA [162]. A case report of two young female patients receiving VPA for epileptic disorders found an exaggerated LH response to growth hormone-releasing hormone [142]. Murialdo et al found that in a female epileptic population, those treated with VPA had a higher LH/FSH ratio in the luteal phase [151].…”

Section: Gonadotropinsmentioning

confidence: 99%

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

Reynolds¹,

Sisk²,

Rasgon³

2007

CMC

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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.

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“…Cocaine administered subcutaneously causes a dose-dependent disruption of estrous cyclicity, reduced serum LH levels, and reduction of ovulation in female rats (211). Valproic acid exerts its effect on hormone secretion by binding to the y-aminobutyric acid receptors and mimicking the effects of this neurotransmitter in both the rat and human (212 Although a great many compounds disrupt the synthesis of T3 and T4, with few exceptions, they can be classified into three main groups according to their basic chemical structure: thionamides (e.g., propylthiouracil and mercaptoimidazole), aminoheterocyclic compounds (e.g., sulfonylureas such as tolbutamide), and substituted phenols (e.g., resorcinol and salicylamide). Derivatives of thiourea, including thiouracils, cause functional hypothyroidism and hypertrophy, hyperplasia, and hypervascularization of the gland (216).…”

Section: Controversy Within the Scientific Communitymentioning

confidence: 99%