PMDD¹ is a disorder characterized by cyclic emotional and physical symptoms that consistently occur during the luteal phase of the menstrual cycle and is prevalent in ~5% of all young and middle-aged women. The disorder includes severe cyclic depression, irritability and mood lability, but also abdominal pain, breast tenderness, headache, and fatigue. Severe PMS² is present in at least 15% of women in fertile age. The premenstrual symptom severity is most intense during the week prior to menstruation and once the menstruation starts symptom severity decreases rapidly and disappears.
The occurrence of negative mood symptoms coincides with the rise in progesterone levels, but it is the subsequent increase in progesterone’s metabolite allopregnanolone that is responsible for the negative symptoms due to its action on the GABAA receptor in the emotional center of the brain. In similarity to the great variability in individual responses to other GABAA receptor active substances, e.g. benzodiazepines, barbiturates and alcohol, women with PMDD/PMS have a deviant sensitivity to the provocation by the GABA-steroid allopregnanolone as compared to healthy women and therefore they experience the negative mood symptoms.