Disorders of reproduction in patients with epilepsy: primary neurological mechanisms.
ABSTRACT Reproductive disorders are unusually common among women and men with epilepsy. They are generally associated with and may be the consequence of reproductive endocrine disorders. Both epilepsy itself and antiepileptic drug use have been implicated in their pathophysiology. This review focuses on how temporolimbic dysfunction in epilepsy may disrupt normal neuroendocrine regulation and promote the development of reproductive endocrine disorders. The particular nature of the dysregulation may relate to the laterality and focality of the epilepsy and some hormonal changes may develop in close temporal relation to the occurrence of epileptiform discharges. In women, reproductive endocrine disorders include polycystic ovary syndrome, hypothalamic amenorrhea, functional hyperprolactinemia, and premature menopause. In men, hypogonadism may be hypogonadotropic, hypergonadotropic or related to hyperprolactinemia. The significance of these reproductive endocrine disorders is that they may contribute not only to sexual dysfunction and infertility but may also have an adverse impact on seizure control.
Article: Epilepsy, Antiepileptic Drugs and Depression: A Triangle of Danger for Sexual and Reproductive Functions in Females[show abstract] [hide abstract]
ABSTRACT: Objectives: To explore the relationship between epilepsy and anti-epileptic drug (AED) and sexual, reproductive and psychological functions of epileptic women. Patients & Methods: The study included 60 women with partial seizures of temporal lobe origin (TLE) and 20 control age-matched women. All women underwent full history taking and sexual interest and function during the preceding week, measured using the Arizona Sexual Experience Scale (ASEX) questionnaire and were evaluated in terms of possible presence of depression using the Beck Depression Inventory (BDI). Fasting, morning blood samples were obtained for estimation of hormonal profile including serum total testosterone, estradiol (E2), sex hormone-binding globulin,(SHBG), leutinizing(LH) and follicle stimulating hormone (FSH). hormone Results: Epileptic women were overweight to obese; 23 were infertile and 47 women had irregular menstrual cycle. Epileptic women had significantly higher serum testosterone and SHBG with significantly lower serum E2 compared to control women. Twenty-three women had right TLE and 16 patients had stopped AED at least 3 months before testing. Mean ASEX score in epileptics was significantly higher compared to controls with significantly higher mean ASEX score in epileptics who had right TLE compared to those who had left TLE and in those on AED compared to those who stopped treatment. Mean BDI score in epileptics was significantly higher compared to controls, with significantly higher mean BDI score in epileptics who had right TLE compared to those who had left TLE, but patients maintained on AED showed non-significantly higher BDI score compared to those who stopped AED. There was a positive significant correlation between presence of TLE and high ASEX scores, BDI scores, serum testosterone and serum SHBG, but showed a negative significant correlation with serum E2. Regression analysis showed low serum E2 and presence of epilepsy as the significant predictors for high ASEX score which was the most significant predictor for high BDI score. Conclusion: Epilepsy has deleterious effects on psychological, sexual and reproductive functions in women and such effect was magnified with AED and with lesions on the right side and showed a close relationship to disturbed sex hormone levels. Key words: Females, Epilepsy, Antiepileptic drugs, Depression, Sexual and ReproductiveMIDDLE EAST JOURNAL OF PSYCHIATRY AND ALZHEIMERS. 01/2013;
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ABSTRACT: Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Generally, a twofold or greater increase in seizure frequency during a particular phase of the menstrual cycle could be considered as catamenial epilepsy. Based on this criteria, recent clinical studies indicate that catamenial epilepsy affects 31-60% of the women with epilepsy. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. However, there is no specific drug available today for catamenial epilepsy, which has not been successfully treated with conventional antiepileptic drugs. Elucidation of the pathophysiology of catamenial epilepsy is a prerequisite to develop specific targeted approaches for treatment or prevention of the disorder. Cyclical changes in the circulating levels of estrogens and progesterone play a central role in the development of catamenial epilepsy. There is emerging evidence that endogenous neurosteroids with anticonvulsant or proconvulsant effects could play a critical role in catamenial epilepsy. It is thought that perimenstrual catamenial epilepsy is associated with the withdrawal of anticonvulsant neurosteroids. Progesterone and other hormonal agents have been shown in limited trials to be moderately effective in catamenial epilepsy, but may cause endocrine side effects. Synthetic neurosteroids, which enhance the tonic GABA-A receptor function, might provide an effective approach for the catamenial epilepsy therapy without producing hormonal side effects.Epilepsy research 05/2009; 85(1):1-30. · 2.48 Impact Factor
Article: Hormonal aspects of epilepsy.[show abstract] [hide abstract]
ABSTRACT: The relationships among hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions that affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy. Abnormalities are most often described for the sex steroid hormone axis, commonly presenting as sexual dysfunction in men and women with epilepsy and lower fertility. Other signs and symptoms in women with epilepsy include menstrual irregularities, premature menopause, and polycystic ovarian syndrome. The evaluation and care of adult patients with epilepsy should include considerations of the common hormonal aberrations that occur in this patient population. Questions about reproductive health disorders, sexual function, symptoms of thyroid disorders, and bone health should be part of the evaluation of all adult patients with epilepsy. Further laboratory or radiologic testing and referral to other specialists to participate in collaborative care may be warranted if underlying disorders are suspected, especially given that many of these hormone abnormalities can result in long-term health risks as well as negatively affect quality of life. AEDs and hormones have a bidirectional interaction that can impair the efficacy of contraceptive hormone treatments and of the AEDs. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this susceptibility to hormonal influences can be used to develop hormonal strategies to improve seizure control in women with epilepsy with use of cyclic PROG supplementation or alteration of the endogenous hormone release. Additionally, development of the neurosteroid analog ganaxolone provides a novel approach that can potentially be used across both genders and all age groups.Neurologic Clinics 11/2009; 27(4):941-65. · 2.34 Impact Factor