Progesterone and GABA Receptors

For most women, progesterone is great for mood and generates calm and tranquility because it converts to a powerful little molecule called allopregnanolone, which actively bathes and calms our GABA receptors.

GABA is a neurotransmitter, or chemical messenger, in the brain. It blocks specific signals in the central nervous system, slowing down the brain providing a protective and calming effect on the brain - facilitating sleep and reducing feelings of anxiety.

However, some women really struggle with progesterone - in fact at times of the menstrual cycle when progesterone is naturally higher - the luteal phase or when they orally take progesterone as part of an HRT plan it has the opposite effect, not calming,but instead creating a heightened anxiety and moderate-to-severe alterations in mood, behaviour, and physical well-being that fall under the umbrella of PMDD.

What the hell is going on here? There seems to be two aspects:

These women appear to have an abnormal response to allopregnanolone (ALLO). While increased ALLO usually makes us feel calmer, in these women ALLO has an abnormal, opposite effect - agitation, anxiety & negative mood changes. One aspect to this seems to be a problem with GABA receptors, being less able to adapt and compensate for the naturally changing levels of allopregnanolone. The result is a sensitivity and the mood symptoms of PMDD.

What can we do? Stabilise the GABA receptors and therefore be better able to “tolerate” the normal ups and downs of progesterone. Magnesium glycinate or bisglycinate because the amino acid glycine is a wonderful tool that seems to really help to calm the GABA receptors.

PMDD or a seeming “intolerance” to progesterone as part of HRT therapy is a severe negative reaction in the brain to the natural rise and fall of progesterone. I explain this in more detail here.