Updated: Jul 21
Oestrogen is perhaps the most well-known female hormone that we associate with sexual development, menstruation (regulates the menstrual cycle with the help of progesterone), reproduction, maintaining pregnancy and vaginal blood flow, thickening the lining of the uterus and keeping it elastic. But oestrogen is a growth hormone and therefore it has other important roles, especially cognitive function and growth of brain synapses and plasticity. It also has a protective effect on bone density, involved in calcium homeostasis, as well as a beneficial on cholesterol levels and cardiovascular health.
Oestrogen Production Pre-menopause
Produced primarily by the ovaries and produced in the placenta during pregnancy. Some oestrogen is produced in small amounts by the pancreas, adrenal glands, skin, brain and adipose tissue. The latter perhaps being a reason why those with higher amounts of fat tissue, that are pre-menopausal, can often suffer with oestrogen dominance, as more oestrogen is produced than a person with a healthy BMI. It is the fluctuations in oestrogen at these times that can cause problems as they are more unpredictable.
Post - menopause
Oestrogen is primarily made by the adrenal glands via the conversion of androgens (our male sex hormones) into oestrogen. Also produced in the liver, brain, bone, adipose tissue, breast. At this stage only small amounts are made in the ovary. In this case, sometimes those with more adipose tissue have an easier time post-meno as more oestrogen will be produced.
High levels of Oestrogen can include: bloating, breast tenderness and heavy bleeding, painful periods, mood swings, breast tenderness, endometriosis, fertility issues and a possible increased likelihood of developing hormone–dependent cancers.
Low levels of Oestrogen can include: hot flushes, headaches, palpitations, insomnia, bone loss, vaginal dryness and brain fog.
Whilst it is true that when your oestrogen levels drop significantly during menopause it is unlikely you will become oestrogen dominant. But if progesterone levels decrease at a faster rate it is still possible to become oestrogen dominant. If you have had a diagnosis of oestrogen dominance and are a little confused, reading below might help you to understand how our body processes oestrogen.
The three types of Oestrogen are:
E1 (Oestrone), our predominant form after menopause, with a weaker biological function and reversible with Oestradiol.
E2 17b Oestradiol. Made in the ovaries and ceases production in post menopause. This is the one that we should perhaps worry about most.
E3 Oestriol is a weakest form but considered by many to be protective, like phytoestrogens. Produced in the placenta in pregnancy.
Removing Old and Used Oestrogen from the Body
Once the oestrogens have performed their function they must be detoxified and removed from the body. Not only are there the three different types as above, but there is a choice of three main pathways used to remove old/used oestrogen.
Phase 1 detoxification begins in the liver by P450 enzymes. The three possible enzyme pathways are often considered the good, the bad and the ugly! They are the CYP1A1, CYP1B1 or CYP3A4 enzymes. An enzyme is simply something that creates a reaction, and which pathways chosen will depend on which enzyme is more available at the time to remove the oestrogen. These pathways produce different metabolites, and with the additional of a hydroxyl group (-OH) they become:
Hydroxyestrogen (2-OH) via the CYP1A1, ‘good pathway’.
Hydroxyestrogen (4-OH) via the CYP1B1; the most potent or ‘bad pathway’. Partly, due to this being form being the most damaging when reabsorbed by the gut.
Hydroxyestrogen (16OH) via the CYP2C and CYP3A4 or ‘ugly pathways’ - not 'overly bad' but not as protective CYP1A1.
So encouraging Oestrogen breakdown via the CYP1A1 seems most beneficial and reduce the toxic effects of high circulating oestrogen loads.
Next comes Phase 2 detoxification, called Conjugation. This is a process where the intermediate metabolites (the formed substances: 2,4 and 16 OH) become more water soluble and then bonded with bile and excreted in faeces. You can think of Phase 2 as ‘holding the hand’ of these reactive molecules by attaching biochemical groups as the oestrogen metabolites are conjugated with a sulphate, methyl group or glucuronic acid.
In methylation pathways, 2OH and 4OH have an methyl group attached to become safer metabolites, stopping them developing into free radicals. The nutrients needed for effective methylation are B vitamins, Magnesium, Zinc, Choline, Betaine. Meanwhile sulphur can be found in cruciferous vegetables, such as broccoli, cauliflower, sprouts and cabbages, an adequate level of molybdenum is also necessary for sulphuration. Limonene, found in citrus fruits, green tea, kombucha and short-chain fatty acids may be valuable for Glucuronidation.
A poor microbiome can cause recirculation of these metabolites however, and this is a really important aspect, as it is a huge driver of oestrogen dominance. We have a variety of microbes in our gut. Oestrobolomes are a collection of microbes found in our gut capable of metabolising oestrogen. An overgrowth in the enzyme beta-glucronidase, especially in cases of dysbiosis or unfavourable changes in the colon for example, has the power to deconjugate oestrogens back into their active form! This allows oestrogen to recirculate and bind to oestrogen receptors rather than being excreted. And these metabolites are actually more reactive than oestrogen itself.
Higher urinary levels of these metabolites are possibly related to post-menopausal cancers ((Brown et al, 2014). 4OH can become a free radial, an oxidant, something that damages cells. Meanwhile 2OH, which has a weak binding potential, is possibly thought to be beneficial (Fuhrman et al 2012).
Therefore our gut integrity is vital! Eating a variety of fermented foods, including kimchi, kombucha, sauerkraut and kefir. Prebiotics feed our good bacteria and they are found in soluble fibres such as chicory, apples and root vegetables.
Perhaps most importantly, is our ability to exit toxins from our body. For this we need fibre, which bind to bile and together absorb the toxins to produce faeces, and why it is important to produce a regular stool each day; constipation can cause the reabsorption of toxins. Fibre is found in vegetables and whole-grains, such as quinoa, buckwheat, brown rice and oats.
Blood tests do not often distinguish between free and bound hormones. If you feel you might be oestrogen dominant and struggling to get a diagnosis then a DUTCH test may help. It is a sample of dried urine to measure oestrogen, progesterone and testosterone, and can separate free and bound hormones compared to a standard test, often obtaining a more accurate result. If you are not postmenopausal it is worth having regular tests over the course of a month rather than getting a single snap shot and possibly take this further with you GP. If you would like support with nutritional supplements and dietary intervention to work alongside your GP, please do get in touch!