Dr. Emilė Radytė explains the ALLO-GABA theory, shifting the focus from hormones to the brain.

Added: 2026-05-06

[00:00:00]The allogabba theory, um, that emerged and is now the leading hypothesis in the field of PMDD research, essentially refers to the fact that progesterone, which rises in the luteal phase, gets broken down into this other molecule called allopregnanolone.

[00:00:12]Allopregnanolone is really special because unlike all other molecules which interact with their own receptors like progesterone interacting with a progesterone receptor, estrogen interacting with an estrogen receptor, allopregnanolone doesn't actually have allopregnanolone receptors. Instead, it interacts with GABA receptors. GABA is a neurotransmitter that is the most neurotransmitter in the brain responsible for inhibitory actions. So, it's the main neurotransmitter that kind of calms you down and it kind of counterbalances all of the excitatory neurotransmitters in the brain. So, it's really important in order to maintain balance in the brain, but it obviously is normally impacted just by GABA except for this luteal phase when suddenly this allopregnanolone molecule starts also interfering with GABA receptors. And while it's exact role is still not clear and this is still an emerging theory, we know that there must be something in the the way that the allopregnanolone molecule interacts with GABA receptors that may be responsible for the paradoxical response. So, instead of calming down and relaxing before your luteal phase, you get this like increased anxiety and irritability and low mood symptoms in the weeks leading up to your period that is a result of progesterone being broken down to allopregnanolone and allopregnanolone interacting with those GABA receptors in your brain. This is a very exciting theory because for the first time it looks at very specific brain mechanisms trying to explain how they're unique women with PMDD and looking at that very minute interaction between allo and GABA receptors and trying to understand how they differ between women who do and do not have PMDD. It still doesn't tell us why some women have PMDD and others don't, but this is certainly a the right step in the right direction.