Authors :
Presenting Author: Maria Kristina Dorotan, MD – Yale School of Medicine
Caryn Dutton, MD – Obstetrics Gynecology & Repro. Bio – Beth Israel Deaconess Hospital; Paula Emanuela Voinescu, MD, PhD – Assistant Professor, Department of Neurology and Department of Women's Health, Brigham and Women's Hospital
Rationale:
Catamenial epilepsy is defined as increases in seizure frequency in relation to one’s menstrual cycle, thought to be due to the neuroactive properties of sex steroid hormones and their concentration fluctuations.1 There is currently no standard of care for treatment for patients with catamenial epilepsy. Hormonal treatments have been proposed and studied, including a large, multi-center randomized, placebo-controlled trial that showed no difference in seizure frequency comparing cyclic progesterone lozenge treatment vs placebo.2 Other hormonal treatments that aim to suppress menstruation thereby decreasing hormonal variations such as gonadotropin-releasing hormone (GnRH) analogues3 and medroxyprogesterone (MPA) have shown efficacy in smaller studies but have not undergone large-scale trials. All these prior studies focused on the most prevalent catamenial seizure exacerbation pattern – perimenstrual.
Norethindrone Acetate (Aygestin) is a synthetic progesterone, which is typically prescribed for gynecologic conditions such as abnormal uterine bleeding, dysmenorrhea, and management of perimenstrual symptoms, and works by suppressing ovulation and menstruation. It is well tolerated with minimal side effects, limited interactions and is a promising intervention for management of catamenial epilepsy.
Methods:
This retrospective chart review performed at Massachusetts General Hospital and Brigham and Women’s Hospital included women aged 21-65 with a diagnosis of epilepsy and prescribed norethindrone acetate for any indication. Data regarding demographics, gynecologic and epilepsy history, indication for hormonal treatment, seizure frequency, anti-seizure medication doses and changes were abstracted from the records. Effectiveness is defined by decrease in seizure frequency and/or seizure freedom at six and twelve months after the initiation of norethindrone acetate.
Results:
The search resulted in 78 patients, of which 29 had definite diagnoses of epilepsy and prescribed norethindrone acetate. Fifteen patients were excluded in the final analysis due to well-controlled epilepsy at baseline, insufficient data regarding seizure and insufficient duration of norethindrone acetate intake to assess for efficacy, among others. Of the fourteen included in the final analysis, six had definite improvement in seizure frequency after initiation of norethindrone acetate. Two had possible improvement in seizure frequency due to concomitant changes in anti-seizure medications, and six patients had no improvement. Notably, six patients achieved seizure freedom after one year and seven patients had improvement in focal to bilateral tonic-clonic seizures. Majority (11/14) of the patients received hormonal treatment due to a clinical diagnosis of catamenial epilepsy.
Conclusions:
This retrospective chart review shows efficacy of sex hormone cycling suppression, which is defined as decrease in seizure frequency and/or seizure freedom at twelve months following norethindrone acetate initiation for patients with epilepsy, with significant improvement in bilateral-tonic-clonic seizures.
Funding: None