Chapter 2: the hormone chain, identifying common problems and where to start looking for answers.
Ok, strap in. Hormone synthesis and function is very complex, but I’ll try and simplify it down for you!
This is a free post for everyone to enjoy – and includes some really useful and important information. The first two posts in this Hormone Series are free and then I will continue it for paid subscribers. So, do sign up if you want to keep following this series and other more in-depth posts based on over 30 years’ clinical experience. You can read the whole series here.
The Chain of Hormone Events
Here’s a general overview – a bit scary, I admit, but can be useful as we go through things. It’s especially useful for tracking backwards from a problem and seeing if a problem is higher up a chain. You’ll see what I mean.
The hypothalamus in the brain stimulates that top line of hormones to be released. It can be easier to follow one particular colour here, so we’ll choose the green thyroid pathway as an example.
So, TRH is released, which stimulates the pituitary to make TSH, which triggers the thyroid gland itself to release T3 and T4, your main thyroid hormones. Simples.
And there are several pathways there that do a similar thing.
In general, the top line triggers the pituitary to release precursors such as LH, FSH and TSH, which then trigger a gland like the ovaries, testes, thyroid, adrenals etc to make an actual hormone. So far, so good.
Those end hormones are initially bound to a protein so they can be transported around the body without having any effect until they get where they need to be. When they get to their destination, the binding protein is released and the free hormone can bind to receptors, which triggers a cellular response allowing the hormones start doing their stuff. That response can be increased or decreased by various factors.
Detoxing the Hormones
When no longer needed, the hormones and their metabolites need to be bio-transformed in the liver and gut – for example, changing fat soluble compounds to water soluble – so that they can then be excreted via the gut, skin, kidneys etc. Some of the intermediate metabolites can still have an effect before final transformation and excretion, so the biotransformation and detox process needs to be optimal and effective, otherwise you end up with excess activity and problems.
So that’s your chain of hormones in a nutshell.
Things can go wrong at any stage of this process and our job is to work out where the problems are specifically and then address them. Is it the hypothalamus or pituitary right at the top of the chain? Not enough precursor being released for some reason? A protein-binding issue? Problems docking at receptors or not being transported there properly? The biotransformation and detox in the liver or gut? The metabolic response not being initiated at the receptor site?
KEY TIP: The trick really is not to look necessarily at the place something is going wrong, but along the chain – where is it going wrong?
A Few Examples of Hormones Going Wrong
Let’s say the pituitary is not releasing enough LH. That then means a man can’t produce enough testosterone and a woman not enough progesterone. The problem is the pituitary.
Or, maybe the pituitary is not releasing enough FSH. This then leads to poor sperm production in men and low oestrogen and follicle health in women. Again, the problem is the pituitary.
Same happens with poor release of TSH for the thyroid, which will result in low T4 (thyroxine) and T3. Ditto: the pituitary.
Sure, you can give extra oestrogen, testosterone, thyroxine or progesterone, but the problem is not at the gland level – there’s nothing wrong with the ovaries, thyroid or testes per se, it’s a low pituitary problem. Fix that. Do you see?
KEY TIP: I often suggest hypothalamus or pituitary treatment if all hormones are low across the board; it’s a likely sign that’s where the problem is. This can solve a lot of the most common problems, trust me.
In this kind of case, we’d need to suss out what is affecting the pituitary, then? Could it be oxidative stress, obesity, medications, too much prolactin inhibitor being released for some reason, for example? We can stimulate the pituitary with glandulars and nutraceuticals, but we should also find out why it is low in the first place. Some people may need medical help for low pituitary function.
Ageing
As we age, some of our receptors and the glands themselves just become less efficient. That’s essentially what happens in perimenopause to some extent. The pituitary is producing tons of FSH as that is high, but it’s not able to bind at the receptors any more or the ovaries themselves are just not as good as they once were – they’re worn out! It’s a bit like our hearing not being as great after a certain age. So, the problem here can’t be the pituitary, it’s further down the hormone chain in the gland in this case.
Low Cholesterol
What about if someone has low cholesterol? I am tired of seeing doctors push down this so-important precursor. We need enough to be able to make hormones. Low cholesterol = low hormone synthesis, simple as.
KEY TIP: If your total cholesterol is below 120 mg/dL or 3.1 mmol/L, that may be the cause of your low hormone levels. Do not push it so low.
Poor Gallbladder Function
A very common issue in perimenopausal women is gallbladder dysfunction. A clue here is when you just can’t handle hormone meds well at all or they even seem to have the opposite effect – because you’re not clearing it out well enough, probably. Bloating and not dealing well with fatty foods is a sign that your gallbladder might need attention. Hypothyroid, long term use of the pill and even HRT can actually cause slow gallbladder function too.
Other issues might be a lack of glutathione to break down environmental hormones like BPA, not metabolising hormones down properly or making them into more dangerous types, having gram negative gut bacteria or just not enough diversity in the gut microbiome.
Anyway, the list goes on.
It’s all pretty complex and we need some detective work. But the real point is that this is why some people just don’t get the response they expect from hormone therapy. It’s not just about plugging a deficiency gap; there could be other reasons why things are going wrong.
Just imagine: if you gave extra oestrogen as the pill or HRT and a person wasn’t metabolising it well enough, or clearing excess from the body as effectively as they should. What is going to happen? You could get higher levels in the body which gives you oestrogen dominance type symptoms, the receptor sites would stop regenerating or allowing as much to dock and eventually you’d not be able to make even the little amount of hormone you were making before you started. Do you see?
Bioidentical topical hormone creams and sprays are a real cause of this type of excess, actually. It is really easy to get a build up in the body from them as hormones accumulate in fatty tissue and these are metabolised differently as you are bypassing the gut. In fact, if you have it on your skin and you are touching partners, even pets – there is a real possibility that they will get an albeit mild, but consistent and significant dose and it may affect their hormone systems too!
KEY TIP: This is actually a good illustration of why it is important to go low and slow with hormone therapy dosing; don’t go in with high doses as you may well get the opposite effect of the one you want, or not be able to clear it and get dominance symptoms. Once you have a build-up, it can take months to try and reduce levels and clear them out, so don’t be too aggressive, especially with topical forms.
It’s a common myth that if you take x amount of y hormone, you will get z response. That just doesn’t stack up, clinically. People metabolise hormones differently, even day to day, so two people who get exactly the same dose and form of hormones can have completely different effects, and the effect you had from it last week may not be the same this week.
It all depends on loads of different factors – what other hormones are around at the time, how stressed you are, what you ate, how you slept, any competing endocrine disruptors or meds in the system, how much pressure there was on your gallbladder or detox systems today – did you drink more than usual yesterday? It’s fascinating, if ruddy annoying, I know! That’s hormones for you.
OK, I hope you found that helpful. I’ll be back shortly with your next (paid) hormone series post, when we will start going through the hormone stages in more depth, looking at what should happen and what might be wrong if it doesn’t. We’ll start with Puberty – gosh, who remembers that nightmare time, poor kids?!
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