Hormonal aspects of epilepsy

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.

Fig 1

Picture of hypothalamic - pituitary – ovarian axis

Fig. 2. Three patterns of catamenial epilepsy. During normal, ovulatory cycles, both perimenstrual (C1) and periovulatory (C2) patterns can occur in isolation or together. During inadequate luteral phase cycles, the (C3) pattern can occur with increased seizures during the entire second half of the cycle

Day 1 is the first day of menstrual flow and ovulation usually occurs at Day 14 in normal cycles. Adapted from Herzog, A.G. [30]

Figure 3

Schematic diagram of allopregnanolone and its neuroactive steroid binding site on the GABA_A-BDZ receptor