Oestrogen / estradiol

Estradiol (E2) is the strongest natural oestrogen. It regulates the menstrual cycle, bone density, mood, cognition and cardiovascular health. Progesterone slows many of oestrogen's effects; when oestrogen predominates relative to progesterone, this is often called “oestrogen dominance” – a term that is not uniformly defined in medicine. β-glucuronidase in the gut can release oestrogen from its bond with glucuronic acid, so that it can be reabsorbed into the blood.

Which oestrogens the body makes

“Oestrogen” is the collective name for a group of hormones. The three most important are oestrone (E1), oestradiol (E2) and oestriol (E3); they differ in the number of their hydroxyl groups and in how strongly they bind to the oestrogen receptors. Oestradiol is the most potent and predominates in women during the fertile years. Oestrone is weaker and becomes the main oestrogen after the menopause, when it is formed mainly in fat tissue from adrenal precursors. Oestriol is the weakest and is made in large amounts above all during pregnancy, in the placenta. Oestrone and oestradiol can be converted into each other via the enzyme 17β-hydroxysteroid dehydrogenase.

How oestrogen is transported in the blood and acts on the cell

In the blood, oestradiol is largely bound to proteins: tightly to sex hormone-binding globulin (SHBG) and loosely to albumin. Only a small free fraction can enter the cells; saliva mainly contains this free fraction. Inside the cell, oestrogen binds to two receptor types, ERα and ERβ, which act as switches for genes in the nucleus. ERα predominates in places such as the uterus, breast tissue and liver, and ERβ in the ovaries, gut, vessel walls and parts of the brain, among others – which is why the same hormone acts differently in different tissues. A third receptor in the cell membrane, GPER, mediates very rapid effects. Oestrogen itself makes the liver produce more SHBG, while insulin and testosterone lower it.

Oestrogen and progesterone – what happens when the balance tips?

Oestrogen and progesterone work in coordination during the cycle. In the first half of the cycle, oestrogen makes the uterine lining grow and forms receptors for progesterone there. After ovulation, progesterone reduces the number of oestrogen receptors and switches on an enzyme that converts oestradiol into the weaker oestrone; in this way it slows growth and transforms the lining into tissue that can accept implantation. If ovulation does not occur or too little progesterone is made – for example in the years before the menopause – this brake is missing, even if oestradiol itself is not raised. The lining can then grow more, the breasts can feel tender, and bleeding can become more irregular or heavier.

Oestrogen recirculation via the gut – what happens with a lot of β-glucuronidase?

The liver makes oestrogens ready for excretion by attaching glucuronic acid or sulphate to them; part of them thus passes with the bile into the gut. Certain gut bacteria make the enzyme β-glucuronidase, which splits the glucuronic acid off again. The released oestrogen can be reabsorbed into the blood through the gut wall – this cycle between liver and gut is called the enterohepatic circulation, and the gut bacteria involved in it are collectively known as the estrobolome. When β-glucuronidase activity is high, more oestrogen is recovered and less is excreted in the stool; when it is low, for example after antibiotic treatment, more is excreted. How strongly this affects the oestrogen level in the blood is still being investigated in studies.

The interpretation is given in your report.