• DOI:10.1196/annals.1286.005
• Corpus ID: 20995334

Pathogenesis in Menstrual Cycle‐Linked CNS Disorders

@article{Bckstrm2003PathogenesisIM,
  title={Pathogenesis in Menstrual Cycle‐Linked CNS Disorders},
  author={Torbj{\"o}rn B{\"a}ckstr{\"o}m and Agneta Andersson and L Andr{\'e}e and Vita Birzniece and Marie Bixo and Inger Bj{\"o}rn and David Haage and Monica Isaksson and Inga-Maj Johansson and Charlotte Lindblad and Per Lundgren and Sigrid Nyberg and Inga-Stina {\"O}dmark and Jessica Str{\"o}mberg and Inger Sundstr{\"o}m-Poromaa and Sahruh Turkmen and G{\"o}ran Wahlstr{\"o}m and Ming-de Wang and Anna‐Carin Wihlb{\"a}ck and Di Zhu and Elisabeth Zingmark},
  journal={Annals of the New York Academy of Sciences},
  year={2003},
  volume={1007}
}

• T. Bäckström, A. Andersson, +18 authors Elisabeth Zingmark
• Published 1 December 2003
• Biology
• Annals of the New York Academy of Sciences

Abstract: That 3alpha‐hydroxy‐5alpha/beta‐pregnane steroids (GABA steroids) have modulatory effects on the GABA‐A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA‐A receptor‐positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle‐linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA‐steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA‐A modulators. A malfunctioning GABA‐A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is “catamenial epilepsy,” when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.