Progesterone and PMDD

18 February 2022

Progesterone and PMDD

For most women, progesterone is good for mood, calms anxiety and promotes sleep,  predominantly because it converts to a neurosteroid called allopregnanolone (ALLO) which bathes GABA receptors in the brain, the major “off switch” in the CNS thereby inducing calm.

Levels of progesterone and its metabolite ALLO rise after ovulation (about 14 days before your period starts), decrease right before the onset of bleeding & remain low during menses & the follicular phase (first 14 days of the cycle).

At relatively high levels, seen after ovulation, pregnancy & with progesterone supplementation, ALLO interacts with GABA receptors, creating a calming, anxiolytic, anaesthetic & sedative effects. However, for some women it seems an abnormal response to progesterone or ALLO lies at the heart of PMS or PMDD.

For them ALLO does not calm GABA receptors but instead can produce anxiety & aggression. And, this appears not to be related to the amount available, but  a “sensitivity“ issue, at the GABA-A receptor. 

It seems PMDD/PMS sufferers are less sensitive to GABA-A receptor modulators in general; such as benzodiazepines, alcohol, and our friend - ALLO! 

GABA receptors on nerve cells receive the chemical messages that help to inhibit or reduce nerve impulses. Prescription medications called benzodiazepines bind to the same receptors as GABA. 

So what do we have in our kit bag that can help sensitise receptors? 

  • Magnesium, glycinate or bisglycinate, containing the amino acid glycine may help to  calm GABA receptors.
  • Taurine is a calming neurotransmitter, that also interacts with GABA receptors, thereby can be helpful to improve PMS & PMDD symptoms.

For women on HRT with progesterone sensitivity, preparations in tablets or patches can be too much, so definitely speak with your prescriber for alternative routes of application.