Reduced benzodiazepine sensitivity in patients with premenstrual syndrome: A pilot study

Psychoneuroendocrinology (United Kingdom), 1997, 22/1 (25-38)

Premenstrual syndrome (PMS) is characterized by cyclical changes in psychological and physical symptoms related to the formation of the corpus luteum and the fluctuations of gonadal hormones. Ovarian steroids have direct effects on neurotransmission, exemplified by the binding of certain metabolites of progesterone to the gamma-amino-butyric acid (GABA(A)) receptor where they exert a facilitating effect on inhibitory neurotransmission. There is also evidence for steroids with inverse-agonist actions on the GABA(A)-receptor with opposite effects on the GABAergic transmission. The purpose of this pilot study was to examine a possible decrease in GABA(A)/benzodiazepine-receptor sensitivity in PMS patients using saccadic eye velocity and self-ratings of sedation as dependent measures. Seven patients with proven PMS and seven control subjects were recruited for the study. Saccadic eye velocity (SEV) and visual analogue ratings for sedation and mood were measured after increasing doses of placebo and diazepam. The PMS patients responded with a significantly less decrease in saccadic eye velocity after benzodiazepine injections compared with control subjects, the difference being most prominent in the luteal phase. This group difference was due to an increased SEV responsiveness to benzodiazepines among control subjects in the luteal phase compared with the follicular phase. The PMS patients in the luteal phase responded with less increase in sedation change scores following benzodiazepine injections compared with control subjects. This group difference in the luteal phase was due to a decreased sedation response to benzodiazepines across the menstrual cycle in the PMS patients. There was no correlation between sedation change scores and SEV in PMS patients. These results support evidence for a reduced or dysregulated sensitivity at the GABA(A)/benzodiazepine-receptor complex in patients with PMS.

Premenstrual syndrome

Trends in Endocrinology and Metabolism (USA), 1996, 7/5 (184-189)

Within the past decade, premenstrual syndrome (PMS) has become the subject of rigorous scientific scrutiny. As a result, diagnostic criteria have been developed, and the pathophysiology of the disorder has been partially elucidated. The preponderance of evidence suggests that the disorder is the result of the interaction of cyclic changes in estrogen and progesterone with specific neurotransmitters. Serotonin and gamma-amino butyric acid (GABA) appear to be especially important in this regard. Increased understanding of PMS has enabled the development of specific treatment modalities that, unlike previous prescriptions, have demonstrated efficacy in rigorous and reproducible studies.