I never intended to write about sex hormones but over the last few years, it has become increasingly clear that there is a connection between sex hormones and thyroid hormones and that some women never get full relief from symptoms until both have been adequately treated. However, I have found that a few women appear to react poorly to the introduction of progesterone, and this leads them to give up too soon. This is why I wrote this article. The parts on reducing adrenaline may also be relevant to men.
Please note that in all cases where I discuss treatment with progesterone, I mean bio-identical progesterone of some kind. Bio-identical progesterone is the only safe form of progesterone that women should ever consider using as synthetic progesterone is linked with cancer.
It is also worth mentioning that in some countries (including the UK), many doctors simply do not believe that replacement with progesterone is needed in any other than a small dosage to protect the lining of the womb. Certainly, in the UK, the NHS doctors believe that estrogen is the only hormone that will resolve post-menopausal symptoms, and that the idea of ‘estrogen dominance’ is nonsense. Women often need to find a functional medicine doctor or a specialist in bio-identical hormone replacement (if they cannot resolve their issues on their own). I fully intend to use the term ‘estrogen dominance’ as I know for a fact that it is a very real issue for many post-menopausal women.
Please see the sex hormone chapter in The Thyroid Patient’s Manual for specific details on testing progesterone and estrogen in post-menopausal women. Estrogen dominance occurs when the woman’s progesterone level is not high enough to balance the amount of estrogen. The book should be really helpful in assessing this. It would take too much space in this article to cover it. You can use this calculator to assess your estrogen to progesterone ratio. This ratio for post menopausal women is usually best at 200:1 or 300:1: https://www.omnicalculator.com/health/pg-e2-ratio
In recent years, I have tried to help some post-menopausal thyroid patients who have estrogen dominance. Estrogen dominance brings with it its own set of symptoms including weight gain, fatigue, mood issues and breast tenderness. It is difficult to treat thyroid problems when estrogen dominance is also present. Estrogen dominance or high estrogen also increases thyroid binding globulin which lowers the free levels of thyroid hormone, see: https://paulrobinsonthyroid.com/sex-hormones-and-cortisol-relationships/
Treating estrogen dominance through added progesterone usually works well. However, in some cases, the progesterone appears to produce a bad reaction. The reaction is similar to having high adrenaline with tension, anxiety and elevated heart rate. I have never really understood this, as surely adding the progesterone would help?
Recently, from talking to several practitioners and reading Dr Michael E. Platt’s book ‘Adrenaline Dominance’, I think I may now understand why this can happen, and what to do about it.
Through working with patients over many years, Dr Platt is convinced that many of them are dealing with excess adrenaline. This can be true for both men and women. Adrenaline is produced when the person is under either physical or emotional stress. Adrenaline and cortisol can also be elevated when the brain is not getting enough blood sugar. They both raise blood sugar through a process called gluconeogenesis, which I have discussed many times in my writings. The net result of the raised blood sugar can be raised insulin, which unfortunately, can cause fat around the stomach, elevated blood pressure, ageing, and very likely type 2 diabetes. The raised insulin also lowers blood sugar, causing insulin-induced hypoglycaemia. In turn, the hypoglycaemia causes more adrenaline. It is a vicious circle. Adrenaline, is implicated in many negative conditions, including anxiety, depression, insomnia, diabetes, IBS, weight gain, early ageing, headaches, addictions and possibly fibromyalgia. Excess adrenaline is great to get you out of danger but otherwise is it not good news!
However, there is good news! Progesterone has an important role in controlling adrenaline. Dr Platt believes that progesterone can prevent the action of insulin at insulin receptor sites and stop the hypoglycaemia. Plus, progesterone appears to directly block the effect of adrenaline. Progesterone might also have an effect on the pancreas cells themselves and prevent excess insulin production.
Dr Platt in his years of practice is convinced of the effect of progesterone on hypoglycaemia, excess adrenaline, and high insulin levels. Unfortunately, there are no studies on this as it is not an area that has elicited much interest from researchers.
Note: progesterone has no single dosage that is usable by everyone. It has to be adjusted to suit the patient. Also treating the patient based on symptoms and signs is far superior to using lab test results. If transdermal bio-identical progesterone cream is used then it is best used on the inner forearms, upper chest, back of the neck or face – where the skin is thin and there is a good blood supply. Often these transdermal creams need to be applied two-three times per day, as the half-life is fairly short. However, there are other forms of progesterone and different methods of use for their absorption (micronised progesterone capsules, buccal lozenges, suppositories, even sublingual drops like Progest-E/Pro-E which is very pure/additive free). One type/use of progesterone may suit some patients but not others patients. The different forms of progesterone, methods of use and dosages are beyond the scope of this article to cover.
Returning to the thyroid patients with estrogen dominance that seem to be intolerant of progesterone. There are at least two aspects to this:
Firstly, there is a concept discussed amongst bio-identical hormone practitioners called “estrogen kickback“, or “estrogen breakthrough”, where the female patient uses too low a dosage of progesterone and the progesterone stimulates the estrogen receptors. The kickback effect is thought to be due to the estrogen receptors being sensitised, or becoming more active, in the presence of progesterone. This is also referred to as ‘estrogen receptor stimulation’ and ‘estrogen receptor antagonization’ in quite a number of research articles. If there is not enough progesterone to balance this estrogen effect, then estrogen dominance occurs with all the symptoms it brings. The main question though is how much estrogen is there to be balanced and how much progesterone will be needed. Some bio-identical hormone replacement practitioners believe that there is far more estrogen in the body than what is measured in the blood, and essentially estrogen is stored in tissues and is also constantly supplied by our estrogenic environment/foods etc. That is why there might be the need for far more progesterone to balance estrogen than mainstream doctors believe.
The estrogen kickback effect can cause far more of a response to the already dominant estrogen effect than any current estrogen dominance issue is already giving the patient. The symptoms can be varied: mood swings, irritability, fatigue, depression, headaches, weight gain, bloating, and breast tenderness, elevated heart rate, hot flashes and anxiety. Plus, the response can be very strong and quite alarming. This may sound contradictory but I have heard this view expressed by many experienced practitioners. However, many patients simply give up attempting to use the progesterone at this stage because they think it is not going to work for them.
Secondly, patients that do have an adrenaline issue, often need MORE progesterone. Success usually comes when the progesterone dosage is increased, step by step, until the symptoms subside. However, many patients just baulk at using progesterone, once they have had any bad symptoms appearing after starting it.
The bottom line, for both the cases above, is that many women simply need to stick with the progesterone they are taking and wait for the symptoms to subside OR that they actually require a much higher dosage of progesterone in order to overcome the issue. Sometimes it is necessary to try different types of progesterone OR different absorption methods (transdermal creams, oral bio-identical progesterone, suppositories etc. are all options these days for bio-identical hormone replacement).
Therefore, when there is estrogen dominance, the presence of adrenaline and estrogen kickback should always be a consideration when dosing progesterone. Progesterone is the only known hormone to actually deal with both estrogen dominance and high adrenaline. Therefore, sometimes, persisting with its use or even increasing the dosage, is often the only way to actually get rid of the horrible symptoms and effects of estrogen dominance and high adrenaline.
It is also worth noting a couple of other important things:
1. For progesterone therapy to work properly other issues may well need to be addressed. I am not going to list all of these but low iron, low ferritin, low B12 are just examples.
2. Also, sex hormones can have an impact on thyroid hormones. So be on the lookout for this and be prepared to adjust thyroid hormone dosage if you think it appropriate.
Finally, progesterone has been largely neglected by mainstream medicine. Despite this, a large and growing number of women are finding that it can often help them. But just like with T3, which is also a natural hormone, it may not always work for everyone. How can you suddenly become intolerant to something you were producing all your life? Both T3 and progesterone are natural substances and should work for everyone. However, sometimes there are people who struggle to use them without symptoms that are too difficult to cope with. This is much more likely to do with other issues, or conditions that the person has, or, as yet, unknown factors, given how scant the research is in this area. What should be done if there is no relief of symptoms on higher doses of progesterone, despite changing delivery methods, addressing other issues, or the symptoms of intolerance are far too difficult to cope with? In these situations, it is recommended to stop the progesterone, or wean it down, as clearly things are not working.
Thank you to Chemaine Linnie for directing me to Dr Platt’s book. Thanks also to Keith Littlewood for emailing with me on this topic. Also, many thanks to Aldona Z. Coldicott for her very helpful input.
I hope you found this article useful.
There are five blog posts (including this one) that relate thyroid hormones, cortisol and sex hormones to each other:
https://paulrobinsonthyroid.com/t3-thyroid-hormone-and-cortisol-relationships-summary/
https://paulrobinsonthyroid.com/cortisol-results-inconsistent-between-saliva-testing-and-blood-testing/
https://paulrobinsonthyroid.com/sex-hormones-and-cortisol-relationships/
https://paulrobinsonthyroid.com/high-low-cortisol-effects-on-thyroid-hormone-and-dispelling-an-internet-myth/
https://paulrobinsonthyroid.com/estrogen-dominance-the-use-of-progesterone-and-high-adrenaline/ (this post)
Best wishes, Paul
Incredibly helpful article, Paul. You are right on target about this. Thank you.