The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: Implications for diagnosis and treatment

Abstract

Despite our understanding of hormonal influences on central nervous system (CNS) function, there is still much to learn about the pathogenesis of menstrual cycle-linked disorders. A growing literature suggests that the influence of sex steroids on neurological and psychiatric disorders is in part mediated by an aberrant CNS response to neuroactive steroids. Although sex steroids such as estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO) influence numerous neurotransmitter systems, it is their potent effect on the brain's primary inhibitory and excitatory neurotransmitters gamma-aminobutyric acid (GABA) and glutamate that links the study of premenstrual dysphoric disorder (PMDD) and catamenial epilepsy (CE). After providing an overview of these menstrual cycle-linked disorders, this article focuses on the preclinical and clinical research investigating the role of estradiol and progesterone (via ALLO) in the etiology of PMDD and CE. Through exploration of the phenomenological and neurobiological overlap between CE and PMDD, we aim to highlight areas for future research and development of treatments for menstrual cycle-linked neuropsychiatric disorders.

Sex as a Biological Variable: Who, What, When, Why, and How

“…Unfortunately, sex differences in these neuroimaging outcomes are understudied. As adolescence and young adulthood are periods of increased presentation of mental health disorders, including those that are female-specific such as premenstrual dysphoric disorder and catemenial epilepsy, it will be imperative to better identify and delineate interactions between adolescent brain maturation, environmental influences, and sex to identify points of vulnerability (Guille et al, 2008;Epperson et al, 2012). To do so, neuroimaging studies must have sufficient sample or effect sizes with respect to male and female participants or outcomes, respectively, to address these critical issues in normal and aberrant neurodevelopment.…”

Estradiol regulates large dense core vesicles in the hippocampus of adult female rats

“…For about onethird of women with epilepsy, seizures fluctuate with the menstrual cycle, termed catamenial epilepsy (Herzog 2008), which is related to fluctuating levels of the ovarian steroids, estradiol and progesterone (Backstrom 1976; Guille et al 2008). Metabolites of progesterone are generally anticonvulsant (Majewska et al 1986; Kaminski et al 2004), whereas estradiol can be proconvulsant or anticonvulsant depending on the dose and duration of treatment, the type of seizure investigated, and which aspect of seizures is measured (Veliskova 2006).…”

GABAergic neuroactive steroids: a new frontier in bipolar disorders?

“…The role of allopregnanolone and THDOC has been studied in a number of pathologies including epilepsy [57], premenstrual syndrome [57], anxiety [58] and mood disorders [59,60]. …”