The current state of postmenopausal hormone therapy: update for neurologists and epileptologists

Appropriate and safe use of hormone replacement therapy (HRT) in postmenopausal women is an evolving saga, triggered by the unexpected results from the first publication of the Women's Health Initiative (WHI) Trial in 2002. These results showed a slight but significantly increased risk of breast cancer, stroke, and dementia with standard HRT compared with placebo. A reanalysis of these results shows that use of HRT within the first few years after the onset of menopause may be associated with decreased risk of dementia and coronary artery disease. However, HRT in its commonly used form of conjugated equine estrogen and medroxyprogesterone acetate can increase seizure frequency in menopausal women with epilepsy; this outcome may be an adverse effect of these neuroactive steroids on the epileptic female brain, which is already in a hormonally deprived state. To explore this possibility, more information about the neurophysiologic activity of medroxyprogesterone acetate is needed and alternatives to this specific HRT regimen should be considered for women with epilepsy.