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Many women ask us about having a blood test to check their oestrogen levels in order to monitor their hormone replacement therapy (HRT). In this article, we explain how and where oestrogen is produced and if and when blood tests are recommended.
Before the menopause, your ovaries make most of your oestrogen although a small amount of oestrogen is also produced by your liver, heart, fat, brain, endometrium and adrenal glands. After the menopause, your ovaries produce very little or no oestrogen and your body relies on your other non-ovarian sites for its production.
Your body is able to make oestrogen from a molecule called cholesterol. It is easy to think that cholesterol is an ‘unhealthy’ or ‘bad’ molecule to have because high levels of it are linked with heart disease. However, it is very important to have some cholesterol in our bodies because it is the precursor molecule for our hormones.
Yes, your body can make three types of oestrogen:
Oestradiol is considered the most important naturally occurring oestrogen. It is the most potent oestrogen; it helps us to feel well and it helps to protect our heart and bones.
Most hormone replacement therapy (HRT) preparations contain body-identical oestradiol. This means that the hormone in it is identical in structure to oestradiol.
The alternatives to oestradiol, used in HRT, include conjugated oestrogens and tibolone. Conjugated equine oestrogens are found in some types of HRT – for example Premarin and Premique. Conjugated equine oestrogens are a mix of oestrogens derived from horse urine. Tibolone is a fully synthetic type of HRT containing molecules that act on oestrogen receptors, though they are biochemically different from oestrogen.
The bulbs and roots of wild yam plants contain a chemical called diosgenin. This chemical is very similar in structure to cholesterol and because of this, it can be modified in labs for the production of hormones including oestradiol.
There are over 600 species of wild yam and some species are now grown specifically as a source of diosgenin for labs to use and make hormones.
For diosgenin to be made into oestradiol it requires a set of chemical reactions that can only take place in a lab setting. Your body cannot turn diosgenin into these steroids.
Before the menopause the amount of oestradiol you produce varies within your menstrual cycle between around 110-1285pmol/L but this range does vary . Levels are at their lowest during the first few days of your period and highest in the middle of your cycle at the time of ovulation. The average level through the cycle is thought to be between 180-370pmol/L for most women.
In the perimenopause, your oestradiol levels become more erratic and can swing from very high to very low.
After the menopause, your oestradiol levels stop fluctuating and become low all the time usually being <73pmol/L .
The National Institute of Clinical Excellence (NICE) does not recommend the routine use of blood tests to diagnose the menopause in their guidance for women over the age of 40. They advise that blood tests for follicle-stimulating hormone (FSH) should be considered in women aged 40-45 with menopause symptoms including a change in the menstrual cycle, and blood tests are important in women under 40 in whom the menopause is suspected. FSH is the hormone produced by the pituitary gland in the brain and stimulates the ovary. Levels of FSH rise and fall during the perimenopause in the same way that oestrogen can. Levels are permanently raised in the postmenopause, when oestradiol levels are permanently low. FSH levels are not useful in monitoring the absorption of hormones from HRT.
In the perimenopause, your oestradiol level can swing erratically and for this reason blood tests to check oestradiol are difficult to interpret and should not routinely be done. You may be experiencing symptoms of the menopause transition but if you check your oestradiol level on any given day it can be normal. If you are taking HRT in the perimenopause, oestradiol blood tests for monitoring can be misleading. HRT does not usually completely stop the dramatic swings of oestradiol, but can increase the lowest levels, helping manage symptoms.
After the menopause, swings in oestradiol no longer occur making this a better time to assess your levels, but they are usually still not very helpful. Your oestradiol level will be low regardless of whether you are experiencing symptoms or not. Some women will experience symptoms ongoing after the menopause for many years and for some women symptoms will start to resolve more quickly. How quickly your body adapts to the low oestrogen level is extremely variable from woman to woman.
Sometimes it can be difficult to know if you are peri- or postmenopausal. For example, if you have a Mirena coil in place or you are taking the progesterone-only pill. Again, you can see that an oestradiol level may not be useful as it can be so variable in the perimenopause. The symptoms, and their impact, are the most important factor in determining treatment.
Routine blood testing is not recommended when you are taking HRT. This is because blood tests to check your oestradiol levels can be prone to error. This means that your oestrogen dose should be adjusted according to your menopausal symptoms.
There is no consensus on when to arrange blood tests to check your oestradiol levels however most clinicians agree they can be considered if:
You should only check blood levels for oestradiol if you are using a patch or gel preparation.
The Lenzetto spray contains a chemical called octisalate which helps to form a depot store of oestradiol under the skin. There are concerns that this makes blood testing unreliable. If you are swallowing oestrogen as a tablet then the liver will affect its metabolism, and absorption relies on the gut. Absorption can be variable – for example depending on when you last ate. These factors mean that blood testing is unreliable.
When a gel or a patch is applied to the skin the oestradiol in it will move across the skin layers into small capillary blood vessels. There are however many factors that can affect this process including:
Oestradiol levels will also vary considerably from the time of application of oestrogel.
Because of these variabilities blood tests can be prone to a lot of error and variation. Even in the same person, results can vary a lot from day to day.
Unlike other hormones, there is no recommended oestradiol level that you should aim to achieve although a good starting point might be to aim for oestradiol levels that are comparable to the average levels in your normal menstrual cycle, which is between 180-370pmol/L .
Some women do appear to feel better with higher oestradiol levels and although there is no upper limit most agree that levels should not exceed 800pmol/L.
If you have received a blood test result demonstrating a high oestradiol level then it is important to first consider the context of this result. Sometimes in the perimenopause very high levels are identified due to your oestradiol swinging and very high results can also occur if your gel has been applied recently. It might be helpful to repeat your blood test first in this setting.
However, if your oestradiol result is likely to be a true reflection of your average level then consideration should be made to reduce your dose if possible. Current guidelines recommend using the lowest dose of oestrogen that controls your symptoms.
High oestradiol levels can increase the risk of bleeding problems and a thickening of the lining of your womb. With time this can increase the risk of womb cancer. If you do require a high or unlicensed dose of oestradiol to control your symptoms then a higher dose of progestogen or use of the Mirena coil should be used to ensure that you have adequate protection for your womb lining.
For more information on blood tests to diagnose the menopause see here.
Check out this short video from Dr Clare where she discusses:
Dr Clare Spencer
Registered menopause specialist, GP and co-founder
Dr Abbie Laing
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Skin contamination by oestradiol gel- a remarkable source of error in plasma oestradiol measurements during percutaneous hormone replacement therapy. Vihtamaki T, Luukkaala T and Tuimala R. Maturitas. 48 (2004) 347-353.
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NICE guidelines (NG23). Menopause: diagnosis and management. November 2015. Last updated December 2019.