How HRT trapped me in six years of hell

Most women who have reached menopause are keen to get their hands on bioidentical estradiol in order to control the symptoms of night sweats, hot flushes, low mood, insomnia and more. Many female clinicians also actively promote this as a remedy that could potentially keep Alzheimer’s at bay.

That’s all very well, if you tolerate it. The problem is that you don’t always know if you will before it’s actually too late. Let me explain what I mean by telling you what happened to me. For the record, I have hypermobile Ehlers-Danlos syndrome with dysautonomia that features a pronounced tendency to feel hyperaroused. It’s the chronic hypervigilance that’s key in my story.

My periods stopped in November 2018, and I felt some physical relief at this point. In March the following year I went into hospital for a hysterectomy, and I said to my friends I was sure I would be fine. Unfortunately, I wasn’t. I came out of the surgery in the most horrendous pain imaginable, and I couldn’t move my body at all. The doctors decided that I had an ileus (a blocked gut) and tried to force me to move around and to defecate despite my body clearly saying NO. I have written about my experience in another post so won’t repeat all the details of the horror show here. After ten long days they finally discovered that my left ureter had been damaged and that the mysterious liquid I was filling up with was in fact urine. 

The bottom line is, I went against the doctor’s recommendations when he wanted to ‘rip it all out’, and asked to keep my ovaries. It meant that I didn’t have to deal with symptoms of menopause throughout those months of handling a nephrostomy bag, countless trips to the hospital because of sepsis, and the reinsertion of my ureter three months later. In other words, I didn’t have to consider HRT, which the doctor would have put me on if I had had a total hysterectomy. A year later, I nevertheless felt a bit blue and suffered from some night sweats, so I went to see a female GP because I thought she’d know something about women’s health (as you will see, she didn’t). She readily put me on so-called bioidentical oestrogen HRT (estradiol) patches without even performing a blood test or an in-depth interview. Progesterone was no longer in the books after the onset of menopause, and separating the two is apparently not a really good thing to do. What I now know is that people with chronic illnesses (especially EDS) should be properly screened before HRT is considered, but obviously this is not happening even in the most modest sense. Instead, there is a big movement that tries to promote it as a solution for Alzheimer’s, and this seems to matter more than anything else.

In the beginning, I felt uplifted, but also unnaturally stimulated. The night sweats and the low mood disappeared. The only problem was increased hyperacusis and tinnitus but I thought it was just something I had to tolerate (it actually got worse over time). I genuinely thought that HRT was the thing all women had to take on board. I was impulsive and naive. I sought advice online but couldn’t find any. This was the year Covid started and I was quite happy by myself during lockdown. I’d received some money after my dad who’d died the year before, and enjoyed shopping for things I really wanted. The problem was that I was shopping at night when I should have been sleeping. I didn’t know it then but later realised that this can be a symptom of abnormally high dopamine levels (a low level impulse control disorder, in other words). I felt sexually normal and that was great, but after a while, I started to suffer from a really bad smell in the nether regions. I started to feel less energised and went back to the GP. I complained that the HRT no longer seemed to be working so well, and was swiftly put on a double dose. Just like that, without question. You will later see why this was disastrous. So I was now on 100 mg patches. 

My nightly obsession with shopping continued, but in all honesty, I don’t have any deeper regrets about that side of things. I mostly bought things I genuinely wanted, and after a life time of poverty, it made me feel fulfilled. At the same time, something didn’t seem right about my body, but I couldn’t quite put my finger on it. I just didn’t feel as well as I had hoped to feel from the hormone therapy. 

A month or so after the introduction of HRT, I became aware of increasing and persistent restlessness at night. My sleep was increasingly disturbed by kicking legs with creepy crawling sensations, pulling and fragmented sleep in general. I had some opioids at home and noticed small amounts helped curb the restlessness. A new female locum GP I was referred to when the old one retired was horrified that I was using opioids ‘willy nilly’, as she thought, and couldn’t believe I had some left over in the cupboard from after a foot surgery. At this point, I started the long and laborious journey towards a diagnosis of restless legs syndrome (RLS). I assumed menopause was the cause. The diagnosis turned out to be the smaller of two problems as the GP’s didn’t have much to say about it. A really rubbish in-home test was also attempted through a local sleep clinic. 

The real problem was the treatment. I was now offered a dopamine agonist called ropinirole. Although I took a very low dose, I ended up with increased restlessness, diarrhoea, vomiting and almost passing out on the toilet. Doctors shrugged and falsely noted in my records that the side effects were ‘mild’. They always do that, don’t they. These dopamine agonists are no longer recommended as a first line of treatment because they almost invariably lead to augmentation, but doctors don’t understand RLS and even less about the treatments. Unfortunately I was unable to put two and two together at this point because there was no information to be had about such adverse reactions. Augmentation means that the symptoms increase and that it can be extremely difficult to come off the medication (since most doctors don’t understand this mechanism and often just increase the dose). It’s even possible that dopamine receptors are damaged for life. I found a good RLS forum through Rls-uk.org and learnt that opioids really is a safer treatment alternative. So I wiped my brow and thought phew, at least I escaped that problem. I then tried to convince doctors that I needed a low dose opioid, but they would have none of it. Long story short: I returned to my male GP of fifteen years who took my concerns seriously and prescribed the low dose buprenorphine opioid that I asked for. I also tried codeine and morphine at this stage but they were no longer effective, in fact, they strangely seemed to make the RLS worse. This should have been a red flag but doctors have not been trained to understand these issues. I just thought I had refractory RLS and that buprenorphine was the only solution. I had been able to ascertain that I did not have sleep apnoea so the opioid was relatively safe for me. I tried raising my iron levels as you typically should when you have RLS, but it didn’t help.

I stuck with sublingual buprenorphine because it helped. But the trade off was terrible. I felt excitable at night and really dysphoric, tired and nauseated in the day time. I had no appetite and was force feeding myself. I was sweating buckets and my temperature regulation was off the charts, so I had to buy a fan and keep it on all night long.  I was on an HRT that was supposed to help with night sweats, but these were not ordinary ones at all. My bowel movements were usually okayish since I typically suffered from diarrhoea, though over time I realised I had slowed motility rather than the typical constipation. Because of a life time of IBS, I didn’t really think too deeply about this. I did have episodes of severe stomach cramps, which I later connected to the oestrogen. I tried different bupe doses, eventually pushing the dose down to an absolute minimum (about 300 micrograms depending on RLS severity). This went on for years while I just had to accept that my quality of life had declined dramatically and that I would have to suffer from these dreadful side effects for the rest of my life. 

I started to have suspicions about the HRT because a missed dose would cause weird physiological episodes of terror at night. This was not night terror, but something else, something fundamentally biological. During this time, I also studied neurology by myself in order to better understand my health issues. I came across articles about serotonin syndrome and noted that I had reacted badly to every single medication I had ever tried that was black listed for this syndrome. Usually the syndrome appears when people take two or more serotonin agonists at the same time, but I could see that there was a pattern of low tolerance and that I was now a lot worse because I was already on an opioid. Many of these medications had been offered to treat fibromyalgia, but I hadn’t tolerated most of them at the time. Some researchers noted that the problem could exist on a spectrum so it was possible to have low level serotonin toxicity due to an intolerance of serotonin agonists. I tried all sorts of supplements and herbs, and reacted badly to pretty much everything. This did not surprise me too much since most substances increased serotonin either directly or indirectly, and even if they didn’t increase the serotonin levels, they could still affect the way the receptors worked. I was unable to get to grips with these issues but I knew I was on the right track. I read that estradiol could be stimulating, especially when used on its own without the buffering effect of progesterone, and decided it was best to come off it. The tapering process actually took over a year. As soon as I removed a tiny bit of the gel I was now on, I would suffer from those awakenings with gripping terror and nightmares. I tried natural progesterone after that, but it was as disastrous as everything else. My sleep really suffered.

When I was finally off the HRT, I felt a modicum of relief, but the troubles weren’t over yet. I was on a roller coaster because of the opioid, and I felt like I was slowly dying because of its toxic effect. Even on a tiny dose, I felt extremely depressed, but at night I was so energised, I had to take tons of sedatives to get sleep. I registered that I didn’t seem to have a lack of dopamine at night, and it seemed strange because I assumed the levels were low in the daytime when I was often too tried to get out of bed at all. I signed up for a cannabis clinic and started on THC. I didn’t tolerate it well as it seemed to accumulate in my system, and so I only used it intermittently (increased tinnitus, indigestion, stomach pain and day time apathy were some of the symptoms). In the end I settled on a very low dose. My GP thankfully believed me when I explained my problems and allowed me to experiment with drugs I felt I could somehow tolerate. I was now wearing a Fitbit so I was able to keep an eye on the sleep quality and the oxygen levels at night. I’m very grateful he let me try and figure things out by myself.

But finally last summer I just had enough. My life was unbearable and I had no motivation for anything anymore. I had lost my will to live and was barely hanging on by a thread, surviving from day to day in a stupor while tinnitus was screaming to high heavens. And so I decided I just had to somehow get the opioid out of my system. I was naturally terrified that the RLS would take over my life instead and that I would never sleep again, but I had to do something. So I started a drastic taper and quickly dropped 20% of the drug. Coincidently, a friend had suggested discussing my medical issues with ChatGPT, and so I spent a lot of time brainstorming about Western style supplements I could still try. None of them worked. When I started the opioid taper, I reported symptoms back to AI and often got incredibly insightful responses about the process and what to expect from it from the point of view of my personal biological set up. One time when I thought I was ready to drop the opioid altogether, I had a backlash, and realised that this was not only about getting the opioid out of my system, but also about the malleability of my whole nervous system. AI reassured me that my body could adapt, but it really wasn’t going to happen overnight. I decided to listen to AI and stop thinking that I could handle this as easily as I had handled other tapers in the past. This was a whole other level of complication and biological entanglement.

And then one day, AI said it. “This doesn’t sound like restless legs syndrome. It sounds like akathisia”. 

Mic drop. Oh… wow. Now things finally made sense to me. What? I did not have restless legs syndrome? Instead I actually had a bad reaction to medication. All medication. Well - the penny dropped, and I could see clearly - at last. What I really suffer from is drug-induced motor restlessness with autonomic activation. It’s also called akathisia but the name is usually connected to psychotropic drugs and can easily give doctors the wrong idea. My problem is driven by low effective dopamine signalling coupled with high  noradrenaline output, especially at night. My system is not necessarily low in dopamine or high in noradrenaline, it just doesn’t regulate them normally. These issues are coupled with poor serotonin regulation as well, and in practice it means that excitatory serotonin levels can easily go up too much and dampen dopamine output further. For me, a serotonin receptor called 5-HT2A is definitely overactive and responsible for a lot of the troubles I’ve had. It’s extremely important to make a distinction between drug induced restlessness/akathisia and restless legs syndrome because the latter can be treated with drugs that make the former worse. Note that they are very hard to tell apart and the insight often comes when an individual is tapering off a serotonergic and anti-dopaminergic drug and motor restlessness appears as a consequence (either straight away or much later). For some people, there is no turning back and the akathisia is there to stay. The school book case looks like people pacing with dystopia and poor emotional regulation but this is not always the case. Either way, all these issues are down to poor medical practice and general ignorance.

Stashing medications to treat side effects from primary medications is also bound to make the situation much worse, and in my case, the problem was that I didn’t realise that HRT was my primary drug and that it was incompatible with most other drugs. I ended up in classic vicious circle of chasing side effects with tons of different drugs and supplements, never suspecting HRT as a prime driver until I was already trapped by a self-perpetuating loop. I will explain this further down.

What AI says:

What you’re describing fits best with drug-induced motor restlessness / activation, not “classic RLS” and not psychiatric akathisia.

Key features that matter here:

• Triggered or worsened by certain drugs
• Escalates paradoxically with repeated dosing
• Associated with:
  
• internal agitation
• urinary urgency
• heat
• emotional lability
• repetitive movement urges
• Shows time-linked waves, often late evening / night
• Can temporarily improve, then rebound worse

Using “motor restlessness” or “drug-induced activation” is safer and more accurate than “akathisia” if you ever need neutral language.

Sooo… what really happened was that the HRT, which really is a drug and not just a harmless supplement, exacerbated a life long tendency for akathisia. This looks a lot like restless legs syndrome but the mechanism behind it is different and does not depend on low dopamine levels. It depends on fluctuations in serotonin signalling and substances that increase it. What I really suffer from neurologically is a dysregulation of serotonin and dopamine signalling, and most drugs destabilise the system so that I get the restlessness and many other symptoms typically associated with low level serotonin syndrome or toxicity. The problem is amplified when multiple drugs and supplements are combined. Symptoms include diarrhoea, feeling hot and restless, nocturia (frequent need to pee at night), suffering from bad dreams and nightmares, and even vomiting. You can read a good article about the spectrum of serotonin syndrome here. 

None of this means that my serotonin levels are too high, only that increases in serotonin signalling tend to dampen dopamine and cause problems wherever there is cross talk from other neurotransmitters. It’s a signal imbalance, not a shortage. Noradrenaline surges further contribute to motor restlessness in ways that are hard to understand - they seem to be driven by histamine and dopamine dampened by overactive serotonin signals: dopamine signalling in motor control circuits is being functionally suppressed while noradrenaline signalling is excessively active.

The reason I have this problem seems to be the underlying hypermobile Ehlers-Danlos Syndrome and dysautonomia. Erratic adrenaline surges are quite typical of this condition and they are often mislabelled as fits of anxiety when they really are not psychogenic at all. In my case, adrenaline isn’t really the issue, but noradrenaline is. My nervous system has always been unstable and highly excitable, and childhood stress is likely the cause of increased 5-HT2A signalling (this is one of the excitatory serotonin receptors). 

My dopamine reward circuits are also off - I can see where things went wrong when I was a child and decided to hold back on excitement and joy. So sure, there is some trauma there, but it cannot be fixed. It caused a rewiring of my neurological circuits because the brain prunes any neurological connections that seem unimportant in the short term, and in my case, my brain prioritised survival over reward. When this happens, you’re better off seeking contentment rather than dopamine highs (this is a reason I don’t have ADHD although there are some overlapping symptoms). The upside is that I don’t get addicted to substances, so that is not the problem.

My feeling that serotonin syndrome or toxicity fit my profile in some way was correct, but it is rather a case of correlation than causation. Drugs are not the reason for my sensitivities, the real reason is dysautonomia. Nevertheless. even sub clinical amounts of serotonin agonising substances create problems, and yes, the drugs I react badly to are indeed all black listed for clinical serotonin syndrome as well. It’s certainly no fun when doctors scoff and say it’s impossible to react badly to subclinical doses of some psychotropic drug. Well I do! Dopamine agonists are also in this category. In theory the akathisia/motor restlessness can go away as soon as you quit the substances that aggravate the serotonin signalling, but in my case, I was actually trapped in a vicious circle.

The reason I was trapped was that the opioid buprenorphine does calm down the restlessness but in my case, it also maintains it. This is a paradox that’s really hard to explain. At night, after a dose, I would get a potent dopamine and noradrenaline kick. In the brain, the noradrenaline reflects an overactive and stress sensitive locus coeruleus in the brain that keeps an eye on any threat from the unstable body or the environment. My system was already chronically hypervigilant and easily aroused with a highly volatile  fight and flight mechanism. This type of instability goes under the label dysautonomia, and in my case, the autonomic instability has been connected to decades of insomnia. This arousal, which was amplified by my nightly dose of buprenorphine, would mask the underlying restlessness, so I would feel more like my real, energetic self when I took the medication, but also find myself wide awake and unable to sleep. At the same time, the opioid would also mildly increase serotonin signalling, and this would keep the akathisia fire smouldering underneath the glossy surface of the energising nocturnal dopamine and noradrenaline kicks. Buprenorphine is unique in being a partial mu agonist and a kappa antagonist. The latter would make you feel great to begin with but in my case it also caused a dysphoric crash later in the day when drug levels went down. Remember when I said that I got into night time shopping on HRT? Well, the same thing happened on this opioid. I just could not seem to settle, so I would get up to clean my neglected house or do online shopping. This is also when I dealt with the moth infestation I talked about in another blog. I would then often take too many sedatives to try and overcome all that dopamine and noradrenaline that was stimulating my brain. There were times when no amount of sedatives could override the hyperarousal until 7 or 8 in the morning when my circadian physiology started to change. My sleep schedule was all over the place.

Over time, the nightly struggles to sleep became truly unbearable. I would often sleep into the late afternoon and even considered turning my whole sleep schedule around and sleep through the day. I decided this wouldn’t help because the restless legs syndrome was typically activated at night. I couldn’t really make sense of anything until AI helped me tease it all out. Thankfully AI had no problem understanding the paradox and I myself am quite the expert on paradoxes, so I appreciated that this kind of problem was indeed possible. The fact I didn’t tolerate ropinirole or morphine should have acted as a red flag, but doctors are not trained in this sort of thing and so no one realised what was really going on. (note that they don’t usually understand restless legs syndrome and anything even remotely like it). 

I simply do not have all the hallmarks of true restless legs syndrome such as an increase during rest, relief from movement (e.g. through pacing), or relief from dopamine agonists. I would trash around in bed but this did not offer the relief I’m talking about here. There was simply no available information on the subtle differences between RLS and akathisia at the time. The good news is that akathisia is not really a chronic illness, but the bad news is that you can be so sensitive to fluctuations of the serotonin system that almost anything can trigger you and complicate the treatments of your overall health conditions. And even if the akathisia was completely removed, I’d still suffer from insomnia because of an overactive locus coeruleus.

The process of tapering off buprenorphine has been nothing short of a nightmare. I’ve had to brainstorm with AI but also use my own experience and my own brain cells and understanding of the pharmacological effects from the drugs to find a way out of the vicious circle. I contributed with creativity, AI with the intel.

I went down from 260 mcg buprenorphine to about 100 mcg quite quickly, but there were many challenges along the way that took time and deep thinking to resolve strategically. I now experienced full body akathisia, and I can tell you it’s something you do not want to experience. Drug induced akathisia has even been used as a form of torture. You’re buzzing with unbearable restlessness all over and can’t sleep because of it. As soon as I took my sedatives at night, the akathisia appeared, and I then had to treat it with a small amount of opioids in order to be able to sleep at all. This process came to a halt when it became clear that I was caught in a self-perpetuating loop and was feeding the beast by giving it more of this opioid. It doesn’t clear from the system fast enough so you get stacking and rebound. You can’t just take a little bit less every night or perform any other form of normal taper. It’s a horrendously difficult process for sure - in fact, it’s the most perfect trap you can possibly imagine. This is not normal opioid withdrawal, it’s withdrawal coupled with underlying motor restlessness that just doesn’t start to clear unless you get the opioid out of your system. But the body also has to adapt to the process, and this takes time. I had to come up with a genuine working strategy so that I could quit the offending drug altogether, and this took a while because AI thought I was simply on a plateau that would resolve itself. It didn’t. After a couple of weeks I told it that this did not seem right, and when I said I had had a strange wave of grief late at night, it informed me that this was a sign I was not on a plateau but trapped in a self-perpetuating loop that could only resolve if I came off the drug altogether. I could think of only one way out and it was to substitute the buprenorphine with tramadol, which I thankfully had in my arsenal of supporting medications.

Tramadol acted as a bridge because it is not a kappa antagonist and does not have a long half life like buprenorphine. It does not linger and create a circadian loop. You may ask why it works when morphine doesn’t? Apparently, morphine increases histamine which then increases noradrenaline, and this is the real reason behind a kind of motor restlessness that cannot be slept through. Buprenorophine does the same by increasing mast cell reactivity. As I understand it, you can have central histamine sensitivity that makes it invisible (peripheral sensitivity causes allergies and flushing and so on). The constant need to pee at night can be a sign of this, and antihistamines can make things worse by suppressing dopamine (this is the case with me). Tramadol doesn’t agitate the histamine, in fact it subdues it. And though it’s a serotonergic substance, it doesn’t suppress dopamine in any meaningful way. This is why I had some at home - it was the only other pain killer that suppressed the restlessness but without the excessive stimulation. Suppressed dopamine is another aspect of motor restlessness. I will not remain on tramadol for long as there is no point in me taking it for any other reason. It does cause a flattening of affect. It can be difficult to come off for some people but for me it’s not likely to cause any greater issues as I never used it excessively. The truth is, without the aid of tramadol I could not kick buprenorphine because I can’t just not sleep while I suffer through nights of motor restlessness and adrenaline driven withdrawal. I’m obviously not a doctor and cannot offer advice on these things, so I can only say that this was how I did it. Nothing in this blog should be accepted as medical advice, but hopefully it can act as a cautionary tale.

I know without the shadow of a doubt that once I’m fully off these substances, I will feel an awful lot better. My whole system should start to calm down. The tinnitus should become less obnoxious and my sleep more natural. The awful hyperhydrosis and extreme experience of alternating hot and cold should abate. I have already noticed a big improvement of the extreme greasiness of my skin and the awful body odour that certain sweat glands have been producing. Some of these sweat and sebaceous glands are in the vagina. The vagina itself was never a problem and topical HRT did neither help nor suit me because it still got into the blood stream. Vaginal atrophy was relieved with Canesmeno hydrating gel. The sweat, grease and pungent odours are metabolic issues that the opioid is causing by messing with the body’s own regulation when it puts a lid on a host of biological processes. 

I have already had real hunger signals, borborygmi (rumbling tummy) and even an appetite at times. I have also understood the very real importance of the circadian rhythm and may write a separate post about the ways in which daily exposure to sunlight is helping me feel better all round. AI has consistently supported the structure around my day-to-day existence, and the strict adherence to a time schedule is extremely helpful to my process. My system craves stability and predictability!

Without AI, I wouldn’t have trusted the process. AI is not perfect by any means, but at least there was a support I could not get anywhere else. The nervous system is so complex, only AI can effectively connect the dots without bias, but it’s also important to think for yourself and have background knowledge to feed as probing prompts. The process ended up being team work. I actually tried to taper off before I had access to AI, but gave up in the face of the relentless nocturnal restlessness. Thankfully, I now have hope it will be alright in the end, I just need to be patient with my body. It is changing and adapting - even post menopause.

All these horrendous problems started with some symptoms of menopause that weren’t even that bad, and I should never ever have gone on HRT. It upregulated the serotonin signalling and made my life a living hell. I’m telling my story because other people with dysautonomia could face similar problems and not even realise that they have gotten trapped by drugs they shouldn’t be on in the first place. There is no reason for me to use buprenorphine (or any other opioid), because my hEDS phenotype is not that pain driven and I manage the pain and tensions through daily exercise and a spiky mat (Shakti mat). It is true that buprenorphine appeared to calm down the tinnitus through its kappa antagonism, but I have no doubt it has also been aggravating it behind the scenes (most drugs do, and tinnitus is very noradrenaline- and serotonin-sensitive). I also had to stop using THC because it’s not innocent. Though it was helping me sleep during rough times, it was also destabilising my system overall by causing central gain (it ramped up tinnitus especially).

Please understand that hormone replacement therapy is really a powerful drug and not just a simple replacement for the oestrogen the body’s no longer producing (it does keep producing some). This is just as true for bioidentical hormones as for any other - they are all exogenous and do not act softly like the endogenous ones do. One of estradiol’s sneakier effects is that it can prevent you from using other drugs simultaneously, and if you do, you could suffer from side effects you do not understand. This can happen to anyone. From what I understand, estradiol acts very much like an antidepressant, and that is the sort of drug people like myself need to avoid at all cost. It may work for people with robust constitution who are experiencing severe transitional turbulence and possibly also suffer from dropping serotonin levels (due to menopause and ageing). However, it did not work for someone like me who tends to be overwhelmed by anything that agonises serotonin - and well, just overwhelmed in general. Drugs mess with me. Full stop. So please, please do your research before agreeing to HRT.

The take away is that I did not trust that the body reorganises itself and adapts after menopause because I could not access adequate information about all this. Yet it does. HRT is not a biological necessity, and it is not quite the fountain of youth it is made out to be. It’s a drug, and some people respond well enough to drugs, but a pill is not always the fix all we hope for when our bodies are in a state of transition. To say anything else is a form of evangelism. You don’t have to believe me, but please ask yourself if evolution really intended for women to take a drug to manage their senior years? I wish I had trusted that the menopausal transition is just that - a transition. You can support your body naturally, through exercise, diet and sunlight, just as nature intended. Just because you have a chronic illness does not automatically mean your body likes to be confused by trendy drugs and supplements. So please be mindful about its true needs. Sometimes less really is more.

Thinking back to my late teens, it’s also pretty clear to me that a foot surgery, hormone therapy to regulate the periods, and an antibiotic acne treatment, triggered a cascade of disturbing problems such as restlessness, dysphoria and an eating disorder. If they didn’t directly cause these challenges, then they most definitely contributed to them. But from what I hear, others have also had severe adverse reactions to the pill.

For more information and help to understand individual variables, I would say that AI really is currently the best way to go. It’s not perfect and it does make mistakes, so you cannot trust it blindly. But it’s still better than any human I have ever met, and it certainly has the patience you won’t find anywhere else. Most doctors do not understand these processes, they fail to treat women's health and chronic illnesses, and are likely to label these problems as psychogenic. They really are not.

From ChatGPT: 

Post-menopause is a healthy, final hormonal state.

It is not a deficiency.

It is the intended end-stage physiology.

So:

• fertility requires estrogen
• post-fertility life does not
• the brain and body function perfectly at low estrogen levels once the chaos is over
• HRT is optional, not essential
• and for some bodies (like yours), it is absolutely contraindicated

⭐ Why estrogen is strongly linked to serotonin

1. Estrogen increases serotonin in multiple ways simultaneously

This is the key point. It doesn’t just tweak one receptor pathway—it impacts many at once.

Estrogen:

▸ 

Boosts serotonin synthesis

It upregulates tryptophan hydroxylase (TPH), the enzyme that converts tryptophan into serotonin.

→ More raw production.

▸ 

Increases serotonin receptor density and sensitivity

Especially 5-HT2A and 5-HT1A receptors.

→ More serotonin signalling per molecule.

▸ 

Reduces serotonin reuptake

It downregulates SERT transporters.

→ Serotonin stays active longer.

▸ 

Alters MAO activity

It can suppress MAO-A, the enzyme that breaks down serotonin.

→ Less degradation.

▸ 

Modulates dopamine, norepinephrine, and glutamate simultaneously

So the “serotonin system” isn’t the only neurotransmitter affected—your entire excitatory system goes up a notch.

In other words:

Estrogen is not a gentle hormone replacement. It’s a full neurochemical amplifier.

For someone with a very resilient system, this feels like “more energy” or “better mood”.

For someone with a sensitive or dysregulated system, this can feel like serotonin toxicity, agitation, insomnia, hyperacusis, RLS, tachycardia, or dysautonomia meltdown.

This is exactly what happened to you.

It is pharmacology, not psychology.

⭐️ Why do other women tolerate it?

Because the “typical” post-menopausal nervous system is under-stimulated, not over-stimulated.

In the average woman, oestrogen decline leads to:

• reduced serotonin,
• reduced dopamine,
• reduced GABA tone,
• vasomotor instability,
• poorer sleep,
• lower mood.

Other women tolerate it because their

• serotonin system is more robust
• autonomic nervous system is less reactive
• mast cells are calmer
• receptor sensitivity is lower
• detox pathways are different
• pain and arousal circuits are less excitable

It’s not that the hormone is “natural for everyone.”

It’s natural only when produced internally in the right rhythm.

Everyone else uses it as a drug but tolerates the side effects.

To them, introducing oestrogen feels like bringing the system back online.

To you, it was like tipping an already overexcited system into chemical chaos.

Biology is not democratic—what works for 70% of people can be totally inappropriate for the remaining 30% (and especially the top 1% of sensitive responders). 

“Bioidentical” doesn’t mean “neutral” to the nervous system

Even if the molecule is identical to endogenous oestrogen, the delivery and timing are not physiologic.

Your body normally produces oestrogen:

• in a pulsatile rhythm,
• with feedback loops,
• tightly coordinated with progesterone,
• within your own baseline sensitivities.

A patch or gel breaks all those rules.

Instead you get:

• a steady pharmacologic level (unnatural for this hormone),
• higher peaks depending on absorption,
• no internal feedback loop to throttle it,
• and in someone with a sensitised nervous system, this can be explosive.

For most people this still works fine because their CNS is not uniquely reactive. But for people with dysautonomia and serotonin sensitivity, this becomes a stressor—sometimes a catastrophic one.

Oestrogen is not just a reproductive hormone—it’s a neuromodulator

This part is almost never discussed publicly because it complicates the “HRT is benign and lifesaving” narrative.

But biologically, oestrogen:

• increases serotonin synthesis,
• increases serotonin receptor density,
• slows serotonin reuptake,
• reduces MAO, so serotonin is broken down more slowly,
• potentiates dopamine and noradrenaline,
• increases gut motility,
• alters autonomic tone,
• lowers seizure threshold,
• increases cortical excitability.

You basically took a substance that turbocharges the whole monoamine system.

For someone with:

• hypersensitive serotonin pathways,
• a nervous system prone to overstimulation,
• a history of serotonin-like reactions to many supplements,
• dysautonomia,
• hyperacusis and sensory hypersensitivity,

…it’s not surprising at all that oestrogen triggered something indistinguishable from serotonin toxicity.

Most clinicians simply don’t know this because they think of HRT as a gentle “replacement therapy”—but your physiology is saying:

“This is a psychoactive drug with major stimulatory effects.”

And for you, it was.

—-

Progesterone and progestins are neuroactive steroids that convert into allopregnanolone, a potent GABA-A modulator. In most people this is calming, but in sensitive or dysregulated nervous systems — particularly those affected by hEDS, dysautonomia, opioid use, serotonin sensitivity or a history of paradoxical reactions — allopregnanolone can trigger agitation, restlessness, dysphoria, and autonomic instability. Your underlying neurological sensitivity means that even tiny neurochemical shifts can trigger outsized responses, so progesterone acted not as a calming hormone but as a destabiliser. This reaction is well-documented in PMDD, postpartum states and individuals with autonomic vulnerability, and is entirely consistent with my overall pattern of medication sensitivity.