Hormone Replacement Therapy in Women with Epilepsy: A Randomized, Double‐Blind, Placebo‐Controlled Study

Harden, Cynthia L.; Herzog, Andrew G.; Nikolov, Blagovest; Koppel, Barbara S.; Christos, Paul J.; Fowler, Kristen; Labar, Douglas; Hauser, W. Allen

doi:10.1111/j.1528-1167.2006.00507.x

Cited by 108 publications

(75 citation statements)

References 19 publications

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“…However, in patients with epilepsy, estrogens being proconvulsant, estrogen therapy might enhance the seizure frequency [Harden et al, 2006]. A series of findings by Women's Health Initiative Memory Study (WHIMS) suggested lack of efficacy in the treatment of cognitive decline or dementia with exogenous estrogens as well as combination therapy Shumaker et al, 2003Shumaker et al, , 2004Espeland et al, 2004].…”

Section: Hormone Replacement Therapymentioning

confidence: 99%

Genetic variability in estrogen disposition: Potential clinical implications for neuropsychiatric disorders

Grover

Talwar

Baghel

et al. 2010

American J of Med Genetics Pt B

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Variability in the physiological levels of neuroactive estrogens is widely believed to play a role in predisposition to several disorders of the central nervous system. Local biosynthesis of estrogens in the brain as well as their circulating serum levels are known to contribute to this pool of neuroactive steroids. It has been well accepted that estrogens modulate neuronal functions by affecting genesis, differentiation, excitability, and degeneration of nerve cells. These actions of estrogens appear to be more prominent in females with higher concentrations and marked variability of circulating serum levels occurring over a woman's lifetime. However, our knowledge regarding the variability of neuroactive steroid levels is very limited. Furthermore, several studies have recently reported differences in the synchronization of circulating and neuronal levels of estradiol. In the absence of reliable circulating steroid levels, knowledge of genetic variability in estrogen disposition may play a determining factor in predicting altered susceptibility or severity of neuropsychiatric disorders in women. Over the past decade, several genetic variants have been linked to both differential serum estrogen levels and predisposition to diverse types of neuropsychiatric disorders in women. Polymorphisms in genes encoding estrogen-metabolizing enzymes as well as estrogen receptors may account for this phenotypic variability. In this review, we attempt to show the contribution of genetics in determining estrogenicity in females with a particular emphasis on the central nervous system. This knowledge will further provide a driving force for unearthing the novel field of "Estrogen Pharmacogenomics." © 2010 Wiley-Liss, Inc.

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Section: Hormone Replacement Therapymentioning

confidence: 99%

Genetic variability in estrogen disposition: Potential clinical implications for neuropsychiatric disorders

Grover

Talwar

Baghel

et al. 2010

American J of Med Genetics Pt B

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“…A double-blind, randomized, placebo-controlled trial was performed with three study groups: women taking singledose combination HRT (0.625 mg of conjugated equine estrogens [CEE] plus 2.5 mg of MPA, or CEE/MPA) daily, double-dose CEE/MPA, or placebo [39]. Five of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency, compared with four of eight taking single-dose CEE/MPA and one of six taking placebo (P= 0.05).…”

Section: Hormone Replacement Therapy In Epilepsymentioning

confidence: 99%

Hormonal Therapy for Epilepsy

Stevens

Harden

2011

Curr Neurol Neurosci Rep

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In 2011, there are greater than 20 antiepileptic medications available. These medications work by modulating neuronal excitability. Reproductive hormones have been found to have a role in the pathogenesis and treatment of seizures by also altering neuronal excitability, especially in women with catamenial epilepsy. The female reproductive hormones have in general opposing effects on neuronal excitability; estrogens generally impart a proconvulsant neurophysiologic tone, whereas the progestogens have anticonvulsant effects. It follows then that fluctuations in the levels of serum progesterone and estrogen throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence based upon the serum estradiol/progesterone ratio. Therefore, using progesterone, its metabolite allopregnanolone, or other hormonal therapies have been explored in the treatment of patients with epilepsy.

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“…As epilepsy is affected by sex steroids, careful consideration must be given to the regimen used. However, the data are extremely limited (Harden et al, 2006;Shen & Stearns 2009). The details of the only randomized trial double-blind, placebocontrolled trial are now described (Harden et al, 2006).…”

Section: Epilepsy and Menopausementioning

confidence: 99%

“…However, the data are extremely limited (Harden et al, 2006;Shen & Stearns 2009). The details of the only randomized trial double-blind, placebocontrolled trial are now described (Harden et al, 2006). This was undertaken in postmenopausal women with epilepsy who are taking stable doses of AEDs and are within 10 years of their last menses.…”

Section: Epilepsy and Menopausementioning

confidence: 99%