Latest / The Sirona Health Podcast: PMDD, Hormones & Mental Health / PMDD: It's Not Your Hormone Levels, It's Your Brain

Transcript

PMDD: It's Not Your Hormone Levels, It's Your Brain · The Sirona Health Podcast: PMDD, Hormones & Mental Health

• 0:04
  Hormones don't just run your cycle.
• 0:07
  They run your mood, your mind, your whole sense of self.
• 0:11
  I'm Dr.
• 0:12
  Georgina Standen, GP and founder of Sirona Health, and this is the Sirona Health Podcast, where we talk about the relationship between female hormones and mental health properly without the mystique and without the dismissal.
• 0:27
  I've said this a few times now across the last few episodes, and I think it's time I actually stopped and properly explained it.
• 0:34
  It's not about how much estrogen or progesterone you've got, it's about how your brain responds to it.
• 0:40
  Today, I want to properly unpack that.
• 0:43
  Where does that idea actually come from?
• 0:46
  What's the evidence?
• 0:47
  And because I think this is the bit that really matters to you, why do two women with completely identical hormone levels end up with completely different experiences of their cycle I think it's worth being honest about where the thinking used to be.
• 1:03
  For years, PMS and PMDD were described as hormonal conditions caused by too much of something or too little of something.
• 1:13
  Too much estrogen, not enough progesterone, that kind of framing, and I understand why.
• 1:19
  It's an intuitive model.
• 1:21
  Something's wrong with your mood, so something must be wrong with your hormone levels.
• 1:25
  But the science has really moved on from that, and I think this next bit is worth sitting with because I know how frustrating it can be to hear.
• 1:35
  Larger studies over and over show that women with PMDD and PMS usually have hormone concentrations that are indistinguishable from women without symptoms.
• 1:48
  So if you've ever had blood tests done and been told everything's normal while you're sitting there feeling anything but normal, you're not imagining it, and you haven't been fobbed off with a bad test.
• 1:59
  The test genuinely is normal.
• 2:02
  It's just not measuring the thing that's actually going wrong.
• 2:06
  So if it's not the level, what is it?
• 2:09
  This is where it gets interesting.
• 2:12
  There's a study I think about a lot where researchers took cells from women with PMDD and exposed them to estrogen and progesterone in a lab setting, and what they found was that the PMDD group showed abnormal patterns of gene expression compared to the control group.
• 2:32
  So the hormone exposure was identical, but the way the cells actually responded to it at a genetic level was different.
• 2:40
  I think that's a really powerful finding because it moves this out of the realm of it's probably psychological and into something you can actually see and measure at a cellular level.
• 2:53
  The body's reaction to the hormone, not the hormone itself, is what's driving symptoms, and this sensitivity isn't limited to estrogen and progesterone either.
• 3:05
  It extends to serotonin.
• 3:08
  This is actually why SSRIs work so well and so quickly in PMDD specifically.
• 3:14
  Women with PMDD often respond within days, which is genuinely unusual because standard depression treatment with an SSRI usually takes several weeks to have an effect.
• 3:26
  The thinking is that SSRIs increase serotonin availability, which helps buffer the brain against those sharp hormonal transitions in the luteal phase.
• 3:37
  So the speed of that response is actually a clue about the mechanism, not just a side benefit.
• 3:45
  Okay, so here's the bit I think really matters for you personally.
• 3:49
  If it's about brain sensitivity rather than hormone levels, that explains something that's always been a bit puzzling, why one woman's PMDD looks completely different from another's.
• 4:01
  Medicine hasn't formally defined subtypes here.
• 4:04
  I want to be honest about that.
• 4:06
  This isn't settled classification.
• 4:08
  But research and clinical practice increasingly point towards a few different biological patterns.
• 4:16
  Some women feel significantly worse as soon as progesterone starts rising after ovulation.
• 4:22
  And I think this is actually worth slowing down on because it's the original explanation for PMDD, the one that's been around longest and still underpins a lot of how we think about treatment.
• 4:34
  So I want to properly walk through it rather than just mention it in passing.
• 4:40
  After you ovulate, progesterone rises, and your body converts some of that progesterone into a substance called allopregnanolone.
• 4:49
  This isn't a side effect or a breakdown product in the sense of waste.
• 4:54
  It's an active neurosteroid in its own right, and it acts directly on a system in your brain called the GABA system.
• 5:02
  GABA is your brain's main calming inhibitory neurotransmitter.
• 5:07
  It's the same system that benzodiazepines like diazepam, Valium work on, and alcohol actually works on it too, which is part of why a drink can feel relaxing.
• 5:18
  So in most women, when allopregnanolone rises after ovulation, it should have a similar effect, gently increasing that calming GABA signal, helping you feel settled rather than wired.
• 5:33
  That's the traditional model of what should happen.
• 5:36
  But in women with PMDD, the research suggests this response can actually flip Instead of allopregnanolone producing the calm, sedating effect, some women's brains seem to respond to it almost paradoxically with increased anxiety, irritability, or agitation instead.
• 5:57
  And the leading explanation for why that happens sits at the level of the GABA receptor itself.
• 6:05
  GABA receptors aren't a single fixed structure.
• 6:08
  They're built from different combinations of protein subunits, and research suggests that in PMDD there may be differences in how those receptor subunits are expressed or how sensitive they are compared to women without PMDD.
• 6:26
  So you've got the same calming molecule arriving at the same receptor system, but the receptor itself may be built or tuned slightly differently, and that difference in tuning is what turns a calming signal into a destabilizing one.
• 6:43
  I think this is genuinely one of the most elegant explanations in the whole field because it explains so much at once.
• 6:51
  It explains why hormone levels look normal, because the allopregnanolone is being produced completely normally.
• 6:59
  It's the receptor response that differs.
• 7:02
  It explains why the luteal phase specifically is the vulnerable window because that's when allopregnanolone is highest, and it explains why some treatments that seem completely counterintuitive actually work, things like GnRH agonists that switch off ovulation altogether or drugs that block the conversion of progesterone into allopregnanolone in the first place.
• 7:29
  If the problem is the brain's response to that specific molecule, then one valid strategy is simply not producing much of it in the first place.
• 7:38
  This traditional progesterone and GABA model is still, I'd say, the best established explanation we have for PMDD, and everything else we've talked about today, the gene expression differences, the individual variation, sits alongside it rather than replacing it Other women don't seem particularly troubled by the rise in progesterone itself, but really struggle as hormones fall away before their period.
• 8:06
  That looks more like a hormone withdrawal sensitivity, where it's the drop that triggers symptoms rather than the level being high or low at any single point.
• 8:16
  And I think this actually explains something I get asked constantly, which is why hormonal contraception can be so unpredictable for people with PMDD.
• 8:27
  Yes, it can help, but the type, the dose, the regimen matter enormously, and some forms genuinely make things worse rather than better.
• 8:39
  Progesterone has what's called a non-linear effect on the brain, so moderate doses can sometimes trigger symptoms, while lower or higher doses are actually better tolerated.
• 8:50
  It's not a straight line when more is worse and less is better.
• 8:55
  It kind of dips in the middle for some women.
• 8:58
  I know that sounds counterintuitive, but it's exactly why trial and error with proper medical guidance tends to be part of getting this right rather than there being one obvious first-line option that works for everyone I don't want to give the impression that hormone sensitivity is the whole story because it isn't.
• 9:19
  Stress, poor sleep, alcohol, and nutrient deficiencies can all amplify how strongly your brain reacts to these hormonal shifts.
• 9:29
  Stress raises cortisol, and that seems to worsen mood instability in cycles that are already sensitive.
• 9:36
  Poor sleep disrupts both the serotonin and GABA systems, which, as we've just talked about, are exactly the systems most involved in PMS and PMDD.
• 9:48
  And alcohol interferes with how progesterone gets metabolized, which can genuinely worsen irritability or low mood for some women, even at levels that wouldn't affect most people much at all.
• 9:59
  So supporting your brain's resilience through lifestyle alongside proper medical treatment where it's needed isn't just generic wellness advice, it's addressing a real part of the mechanism.
• 10:13
  So to bring today together, this isn't about broken hormones.
• 10:18
  Your levels are very likely completely normal, and that's genuinely not a dead end, it's actually the whole point.
• 10:26
  What's different is how your brain, your cells, your serotonin and GABA systems respond to those normal everyday hormonal changes.
• 10:36
  And because that sensitivity looks different from woman to woman, some more affected by the rise, some more affected by the fall, treatment really does need to be personalized rather than following a single standard protocol.
• 10:52
  I think understanding this also explains something we touched on a couple of episodes ago, why diagnosis relies on tracking your symptoms rather than a blood test.
• 11:04
  You're not looking for an abnormal number, you're looking for a pattern of abnormal response.
• 11:11
  Next time, I want to build on this properly and bring in a newer piece of research that's actually trying to map out these different sensitivity patterns formally, something called DASH MC.
• 11:23
  I think it's genuinely one of the most exciting developments in how we understand this condition, so I'm looking forward to that one That's it for today.
• 11:33
  I'm Georgina.
• 11:34
  Thanks for listening.
• 11:36
  A quick note before you go.
• 11:37
  This podcast is for general information, not individual medical advice.
• 11:42
  It doesn't replace seeing your own GP or a specialist.
• 11:45
  So if anything you've heard today feels relevant to you, please do talk to someone, and if you're struggling, please reach out to your GP, to someone you trust, or to a crisis line if you need one right now.
• 11:58
  You can find Sirona Health and book your appointment at sironahealth.co.uk.
• 12:03
  See you next time