Sex Hormones and Cortisol Relationships

I was not going to write this post. I never even thought that it required writing. However, there are so many differing views expressed on the Internet, on other peoples’ websites and by some doctors who practice in this area, that I felt that I ought to write something. It will at least give me a simple way to answer future questions with a link to this blog post.

Note: this post is mostly related to women as this is where the interaction between sex hormones and cortisol appears to have the most relevance.

I use the terms estrogen and estradiol (which is the main estrogen hormone) somewhat interchangeably. In the UK and parts of Europe ‘estrogen’ is called ‘oestrogen’, and ‘estradiol’ is called ‘oestradiol’.


Is there a relationship between estradiol and cortisol?

I will deal with this in two parts: higher estradiol and then lower estradiol.

Can high levels of estradiol lower cortisol?

Estrogen does not ‘control’ or ‘suppress’ cortisol. The effect is far milder than that. However, if estradiol is raised significantly, it does tend to reduce cortisol production as well as impact cortisol activity in the tissues. This is why more women than men tend to have trouble with hypocortisolism and autoimmune diseases.

‘Estrogen dominance’, where estradiol is not matched to enough progesterone, can have the same effect and cause a tendency towards lower than ideal cortisol. It can also lead to autoimmune conditions, like Hashimoto’s. There is a useful blog post from Izabella Wentz on estrogen dominance and the connection to Hashimoto’s which I will provide at the end of this blog post.

It is also possible for increases in estrogen levels as a result of HRT to reduce free thyroid hormone levels. There is research that shows that higher levels of estrogen can increase thyroid-binding globulin (TBG). TBG binds to T4 and T3 and limits the bio-availability of both, i.e. it lowers free levels of both T4 and T3. So, increased estrogen during HRT can result in lower FT4 and FT3 levels in some cases. This can also have a knock-on effect on cortisol as cortisol production is sensitive to FT3 levels.

What about low estradiol levels and high cortisol?

Conversely, low estradiol does not cause high cortisol. Women in menopause, with almost no estrogen in their bodies, do not normally have high cortisol levels. However, they often do have slightly improved cortisol levels and tissue effects compared to when they were menstruating. So, for many women with insufficient cortisol or chronic inflammation, menopause can often bring some improvements.


What should someone high cortisol do?

A person who has very high cortisol levels needs an evaluation for Cushing’s syndrome or Cushing’s disease (a type of Cushing’s syndrome caused by a pituitary tumour that over-secretes ACTH). If there is no tumour their cortisol levels may be an appropriate response to stress or other diseases. If no other condition can be found, one form of treatment often recommended is to take sublingual DHEA to counteract and balance the high cortisol (as long as they do not already have high DHEA).

What kind of dose of sublingual DHEA can a woman with high cortisol and low DHEA take? For most women, 12.5 mg (1/2 of a 25 mg tab) is a good dose often used by doctors who regularly treat high cortisol and sex hormone imbalances. 25mgs/day is a fairly typical dose if DHEA is very low. Some women can take more without getting adverse symptoms, e.g. acne or hirsutism.


How can estradiol replacement affect blood cortisol tests and saliva cortisol tests?

Those patients on estrogen replacement can have higher blood cortisol than saliva cortisol. This is because estrogen increases cortisol binding globulin (CBG) and falsely elevates any blood cortisol. So, patients who need to do a cortisol blood test or a Synacthen test (ACTH Stimulation test) need to be off estrogen replacement for 8 weeks prior to the test. The estrogen replacement tends to leave the free cortisol levels the same, but blood cortisol levels can be much higher than normal.

I believe that this is because the hypothalamic-pituitary-adrenal axis (HPA), uses free cortisol as its input. Estrogen replacement raises CBG, thus binding more of the free cortisol to protein. The HPA responds by requesting the adrenals to make more cortisol to compensate for higher CBG. The net result is that all cortisol blood tests can show falsely inflated cortisol levels. Whilst the free cortisol in saliva tests remains unaffected. Note: the same thing will occur in those women with unusually high natural estrogen levels.


Finally, what about the ideas of ‘progesterone steal’ and ‘pregnenolone steal’?

These are ideas that you see all over the Internet. I commit to the category of Internet Myths and this is why:

The structure of the adrenal glands is the same in men and in women – this includes the pathways to cortisol production.

Women’s progesterone levels are usually much higher than men’s but only when they are cycling and getting ovarian progesterone production. When cycles are finished and the estrogen and progesterone levels fall, it is the small background production of these hormones by the adrenals that continues. This background production of progesterone and estrogen is the same level as in men – because we share the same physiology of the adrenals.

Healthy men (and women) of any age continue to have good cortisol levels and are able to increase cortisol production in times of stress. This does not involve any increase in progesterone in the bloodstream. Any intermediate step through progesterone is entirely internal to the adrenal glands. The major source of raw material for cortisol is cholesterol.

So, the argument that a woman has low progesterone because the adrenals are using blood progesterone to make cortisol is specious and simply misleading.

Many women can have very low progesterone but excellent cortisol levels (because the cortisol production pathway begins with cholesterol). Therefore, stringent dieting, and the low cholesterol that can result, can often be the worst thing for patients with low cortisol.

So, the entire idea that someone with low progesterone will have low cortisol OR that they have low cortisol because they have low progesterone is flawed.

This does not take away from the need to have progesterone at a good healthy post-menopausal level and to have it balanced with the right level of estrogen in post-menopausal women. Fixing a low progesterone level, especially one that is not balanced against the estrogen level, is a good thing and will often lead to the patient feeling far healthier.


Here is a related blog post:
https://paulrobinsonthyroid.com/cortisol-results-inconsistent-between-saliva-testing-and-blood-testing/


Here is Izabella Wentz’s estrogen dominance blog post:
https://thyroidpharmacist.com/articles/estrogen-dominance-as-a-hashimotos-trigger/
 


I hope you found this blog post helpful.

Best wishes,
Paul

Paul Robinson

Paul Robinson is a British author and thyroid patient advocate. The focus of his books and work is on helping patients recover from hypothyroidism. Paul has accumulated a wealth of knowledge on thyroid and adrenal dysfunction and their treatment. His three books cover all of this.

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6 Comments

  1. Sue Wilkinson on 2nd April 2022 at 2:02 pm

    Being under a menopause specialist, I have found that the current “more is better” idea of pushing oestrogen levels ever higher for menopausal women is not good for me. I can feel better inside my head. Clearer thinking and better mood, but over time as the oestrogen level builds up my legs swell and hurt so much walking is impossible. I can barely move, literally dragging myself upstairs with my hands and unable to go shopping, and I feel utterly exhausted. Because it takes time for oestrogen levels to build up, it took me a long time to realise that this was happening. Although I didn’t know why it was happening. If I reduced my oestrogen dose back down I would reduce the swelling and pain a lot quite quickly.

    It annoys me that these specialists don’t look outside the immediate box of their specialty because it’s causing problems. I now know that I need more oestrogen than I was getting on my own, but I must not push the level too high. I want enough to protect my bones, that’s enough.

    • Paul Robinson on 2nd April 2022 at 2:42 pm

      Sue,
      I agree with you.
      The minimum needed to deal with symptoms is usually the best approach with any hormone.
      Once symptoms are dealt with that is often enough.
      Best wishes, Paul

      • Sue Wilkinson on 7th April 2022 at 1:30 pm

        I have just got my blood results back, which include oestrogen, and yes, I think they are too high for me. They are over the top of the reference range by quite a way. Time to reduce the dose. It is odd though, the product I use is supposed to be medium strength and many complain that it’s too weak. You don’t get results like mine from a medium strength oestrogen replacement. Is there any evidence to say that T3 dosing can increase the body’s own oestrogen production after menopause?

        • Paul Robinson on 7th April 2022 at 5:24 pm

          Hi Sue,
          T3 can help to stimulate the hypothalamic-pituitary system. This is where any remaining oestrogen and progesterone and testosterone come from after menopause. So, T3 can support this. Sounds like reducing the replacement oestrogen a little would be helpful. You should discuss this with your doctor.
          Best wishes, Paul
          p.s. this is likely too detailed and specific to you for a website question. You have my email – better to use that probably.

  2. Lou on 19th April 2022 at 2:36 pm

    Good Afternoon,
    Please could you give me some guidance as I have all the hypothyroid systems , my mum has had hyper and hypo and a thyroidectomy . I take after her and feel that many of my symptoms are pointing toward this as a diagnosis but my readings are always apparently “normal” I’m at a loss as to what to do next ? Any pointers please would be so welcome, thank you for reading ….

    • Paul Robinson on 19th April 2022 at 6:25 pm

      Hi Lou, I would read ‘The Thyroid Patient’s Manual’ book. It will enable you to assess your own (apparently normal) results.
      You would need FT3 as well as TSh and FT4 – sometimes doctors do not test FT3 and ignore it being lowish in the range.
      The book will give you the knowledge to assess things yourself and ask questions of your doctor and request additional tests.
      Best wishes, Paul

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