Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on the seizures' frequency of postmenopausal women with epilepsy - A systematic review.

BACKGROUND Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anti-convulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. METHODS PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the last five years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the Revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tools. Results Of 497 manuscripts screened, thirteen studies were included, including three human studies. One cross-sectional study showed a decrease in seizures' frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls and a Randomized Clinical Trial found a dose-dependent increase in seizures' frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. Discussion and Conclusion There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential and prospective registries are needed for monitoring in this population.