Medroxyprogesterone acetate (MPA), a synthetic progesterone, was added to the antiepileptic drug regimen of 14 women who had uncontrolled seizures. Of the 11 women who developed amenorrhea, 7 reported fewer seizures during MPA therapy. Overall reductions in seizure frequency averaged 30% (n = 11), declining from a baseline 8.3 +/- 5.8 seizures per month to 5.1 +/- 4.1 seizures per month (p = 0.02). No serious side effects were encountered, but spotting was common. These preliminary data suggest further evaluation of MPA for catamenial seizures.
"In fact, progesterone is poorly absorbed orally and has a short half-life, so that it must be administered multiple times per day. Over a 3-month period, 72% of the women reported a decrease in seizure frequency and the average daily frequency decreased by 55%.66 Medroxyprogesterone acetate, a synthetic drug, can also reduce seizure frequency.67 "
[Show abstract][Hide abstract] ABSTRACT: Catamenial epilepsy is defined as a pattern of seizures that changes in severity during particular phases of the menstrual cycle, wherein estrogens are proconvulsant, increasing the neuronal excitability; and progesterone is anticonvulsant, enhancing GABA-mediated inhibition. Thus, changes in serum estradiol/progesterone ratio throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence. To date, there are no specific drug treatments for catamenial epilepsy however, non-hormonal and hormonal therapies have been proposed. The aim of this review is to report preclinical and clinical evidences about the relationship between female reproductive steroids and epileptic seizures, and to describe treatment approaches for catamenial epilepsy.
International Journal of Women's Health 09/2012; 4(1):535-41. DOI:10.2147/IJWH.S28872
"Studied hormonal therapies include medroxyprogesterone acetate or cyclical natural progesterone. Medroxyprogesterone acetate given either orally (10 mg 2–4 times per day) or as an intramuscular injection (120– 150 mg every 6 weeks) resulted in improvement in seizure frequency in a small case series of women (Mattson et al., 1984). Two open-label trials of 200 mg natural progesterone lozenges also found significant improvement in seizure frequency (>50% reduction) (Herzog, 1995, 1999). "
[Show abstract][Hide abstract] ABSTRACT: Epilepsy and antiepileptic drugs (AEDs) affect hormones and neuroendocrine systems, which may result in a change in the seizure threshold (catamenial epilepsy) or in comorbidities including sexual dysfunction, reproductive dysfunction, and abnormalities in bone health. Catamenial epilepsy occurs commonly in women with epilepsy. The most commonly reported and studied mechanism proposed to explain why some women have a catamenial seizure exacerbation relates to cyclic changes in reproductive steroid hormones. Women and men with epilepsy have a higher than expected prevalence of sexual dysfunction. The epilepsy syndrome and localization influence the presentation of sexual dysfunction. Reproductive dysfunction occurs in both men and women with epilepsy. As with sexual dysfunction both the epilepsy syndrome and specific AEDs influence the presentation of reproductive dysfunction. Persons with epilepsy have an increased risk of fracture secondary to decreased bone mineral density (BMD), altered bone quality, and a propensity to fall because of either seizures or side effects of medication. Some AEDs are associated with abnormalities in BMD and bone and mineral metabolism.
"Zimmerman and colleagues (1973) used depot administration of MPA to treat a woman with catamenial seizures. Mattson et al (1984) found that MPA produces a 39% reduction in seizure frequency at a mean follow-up of 1 year. Suppression of seizures was evident when the patients were treated with parenteral MPA at dosages that were designed to eliminate menses. "
[Show abstract][Hide abstract] 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. DOI:10.1016/j.eplepsyres.2009.02.017 · 2.02 Impact Factor
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