Action of Progesterone and Progesterone Metabolites in Menstrual-Cycle–Related Disorders
Article first published online: 11 JUL 2008
© 2008 the Author. Journal compilation © 2008 American Headache Society
Headache: The Journal of Head and Face Pain
Special Issue: Neuroactive Steroid Effects on the CNS: Cognitive Function and Migraines
Volume 48, Issue Supplement s2, pages S90–S98, July/August 2008
How to Cite
Sundström-Poromaa, I. (2008), Action of Progesterone and Progesterone Metabolites in Menstrual-Cycle–Related Disorders. Headache: The Journal of Head and Face Pain, 48: S90–S98. doi: 10.1111/j.1526-4610.2008.01201.x
- Issue published online: 11 JUL 2008
- Article first published online: 11 JUL 2008
- premenstrual dysphoric disorder;
- γ-aminobutyric acid receptor;
Progesterone and progesterone metabolites are important modulators of central nervous system function through their interactions with the γ-aminobutyric acid (GABA)A receptor. GABA, neurosteroids, and other modulators of GABAA, such as benzodiazepines, barbiturates, and alcohol, typically inhibit neuronal excitability. The resulting anxiolytic, anticonvulsant, sedative, and anesthetic effects are involved in mood, response to stress, and cognition.
The impact of neurosteroids has been demonstrated in women with premenstrual dysphoric disorder: onset of negative mood symptoms has been correlated with peak progesterone levels, and symptoms intensified with progesterone withdrawal in the late luteal phase of the menstrual cycle. These symptoms were not present during anovulatory cycles without the corpus luteum, the primary source of progesterone and metabolites.
The focus of this article is the paradox of why high levels of progesterone and neurosteroids, which typically are associated with anxiolytic activity, instead induce irritability, anxiety, and mood fluctuations in women with premenstrual dysphoric disorder.