All hail progesterone.

by | Sep 3, 2020 | Uncategorized | 2 comments


But, to get to the punchline, we’re going to have to go over a few terms that aren’t particularly user-friendly. The first is allopregnanolone, which is a neurosteroid that gets released when your body is metabolizing progesterone. The second is γ-aminobutyric acid [aka GABA], which is a neurotransmitter that slows the brain down and makes you feel ahhhhhhhhhh. And one of the reasons that I love progesterone so much is that allopregnanolone – its little metabolic freebie – stimulates GABAA receptors, which can do all kinds of cool stuff in the brain.

Now, this might not sound very exciting, but let me remind you that one of the big reasons that people do things like drink wine and take Xanax is for their potent GABAA receptor action. GABA receptor stimulation makes us feel relaxed. And that’s a feeling that most of us can really wrap our arms around, especially now. So, the idea that we can have our GABAA receptors stimulated by simply metabolizing progesterone – which our body needs to do anyway – is pretty awesome.

And I’m not the only one who thinks so. There is a growing body of research that shows that allopregnanolone – because of its amazing GABArific effects – has a number of therapeutic benefits for the brain. Here is a great review of this literature if you want to read more about the science. What this research finds is that allopregnanolone has potent anti-anxiety and anti-depressant effects, it makes it easier for people to fall and stay asleep, and it can be used effectively to treat seizures and symptoms of alcohol withdrawal.

Now, here’s where things start to get interesting. When you put this all into context, we can make some predictions that might be meaningful to you. First, we can predict that times in the cycle when progesterone is high (the luteal phase), women should feel less anxious and depressed, they should sleep better, and they should be less likely to get seizures or migraines (the neurotransmitter activity involved in both are very similar) than at points in the cycle when progesterone is low. We might even find that women with alcohol dependencies are better able to abstain from alcohol use during this phase of the cycle than during the follicular, ovulatory, or menstrual phase.

But what about women women PMS? Or PMDD? Don’t they feel worse during this phase of the cycle than they do at the others?

Yes. And it turns out that allopregnanolone and GABAA receptors have something to do with this, too. The research, which is summarized nicely in this review article, suggests that PMDD may be caused by impairments in the interaction between allopregnanolone and GABAA receptors. Although women without PMDD are able to dynamically adjust their numbers of functional GABAA receptors, allowing them to experience the amazingness that is GABAergic activity, women with PMDD aren’t so lucky. They aren’t able to adapt to dynamically changing levels of allopregnanolone across the cycle, which can result in mood problems and poor regulation of the stress response. This is why the birth control pill – which irons out women’s hormonal fluctuations and replaces them with a constant daily dose of synthetics – can be therapeutic to women with PMDD.

It is also interesting for me to think about what this means for women on the pill and women going through perimenopause / menopause. Given that women on the pill have extremely low levels of progesterone (and the synthetic progestins in the pill do not release allopregnanolone), we can predict that they will have a higher incidence of mood disorders, sleep disturbances, and might even have a harder time kicking alcohol dependencies than their naturally-cycling counterparts. And – as I talk about in my book – there is evidence for the first of these things, with the pill being associated with an increased risk of mood disorders. I am super-curious about the second two. I am currently plotting ways to include questions about these things in my upcoming research.

It’s also really interesting to think about this as it relates to perimenopause (which I am totally going to rebrand with a better name as soon as I think of one – the word perimenopause feels totally unacceptable to me). During this hormonal transition, our hormone levels drop, which wreaks all kids of havoc on the body and brain. And among the havoc it wreaks is that it makes women angry, anxious, and depressed. It seems likely that changes in GABAergic activity resulting from diminishing levels of progesterone could have something to do with this… and research suggests it may. If you are perimenopausal and pissed off, it’s not your imagination. You may be seriously lacking GABAergic activity, which can make you anxious, angry, sad, and more likely to want that glass of wine to help take the edge off. It doesn’t need to be this way. I recommend talking to your doctor or naturopath about if you think your mood-related woes may be linked to low progesterone. She may recommend supplementing with bio-identical progesterone or trying one of the non-hormonal GABA hacks below.

The good news is that there are ways that we can increase GABAergic activity on our own. Exercise, meditation, yoga, eating fermented foods with probiotics (or kombucha! which is my favorite non-wine-based way to feel GABArific), and supplementing with magnolia bark, valerian root, or lemon balm. Each of these recommendations are backed by research and worth exploring if you think you could benefit from some additional GABA-related action in your life.


  1. Very good and interesting information in this article. I was wondering, does the bio-identical progesterone produce allopregnanolone?


  2. Amazing article! One thing nobody seems to talk about is the change in progesterone levels throughout the luteal phase, and how this affects GABA-a activity. That is, they talk about the luteal phase as though the same thing is happening throughout, but the reality is, progesterone rises during the first half and falls during the second half, so shouldn’t this produce opposite effects on the brain? I ask because, in the week following ovulation, I am like Rumplestiltskin… I could sleep all day! But after that glorious week, I can’t sleep much at all, and my insomnia gets progressively worse until I get my period and finally have some relief. Everywhere I read, authors only seem to treat the second half of the cycle as uniform. I’d love to hear your thoughts on this!


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