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Oestrogen metabolism in men and women

Our exposure to oestrogen begins in foetal development and too much oestrogen, or the wrong ratios of oestrogen, can lead to hormonal imbalances in both men and women. Supporting phase I and phase II liver detoxification processes can help support healthy metabolic pathways of oestrogen in the liver.

3 types of oestrogen
Oestrogen is a steroidal hormone produced from the building blocks of cholesterol and testosterone and is an umbrella term used to describe three different types of oestrogen made by the body known as:

  • Oestrone (E1) - produced in the ovaries/testes and peripheral tissues
  • Oestradiol (E2) - produced in the ovaries/testes
  • Oestriol (E3) - produced via the metabolism of E1 and E2 in extra-ovarian/testicular tissues, where testosterone is converted into E1 by an enzyme known as aromatase.

E2 is the most potent form of oestrogen, while E1 and E3 only provide weak oestrogenic activity. Oestrogen accelerates and stimulates cell growth in all oestrogen sensitive tissues and, while the majority of oestrogen is produced in the ovaries/testes, fat cells, adrenal glands, the liver and breast tissue can also produce oestrogen.

Xeno-oestrogens found in the environment
Xeno-oestrogens, also known as ‘endocrine disrupters’, are profound hormonal disruptors structurally similar to oestrogen that mimic the activity of oestrogen in the body. Xeno-oestrogens can be found in our environment in pesticides, herbicides, drugs, fuels and plastics e.g. dioxins and polychlorinated biphenyls (PCBs).

Controlling oestrogen
Healthy oestrogen levels are controlled and finely balanced by positive and negative feedback loops between the brain (hypothalamus and pituitary gland) and the ovaries/testes. Excess oestrogen occurs when either too much oestrogen is produced, excess oestrogen is not cleared effectively from the body, or through exposure to xeno-oestrogens.

Phase I and phase II liver detoxification
Circulating oestrogens are metabolised in two stages: phase I and phase II liver detoxification. E1 and E2 are converted to three ‘hydroxy’ metabolites by the liver during phase I detoxification:

  • The good: 2-hydroxyoestrone (2-OH)
  • The bad: 16-hydroxyoestrone (16α-OH)
  • The ugly: 4-hydroxyoestrone (4-OH)

2-OH is considered favourable with a protective effect against cellular proliferation and other oestrogen related conditions while 4-OH and 16α-OH are considered unfavourable with proliferative effects and are responsible for many oestrogen related conditions.

Ratios between 2-OH, 4-OH and 16α-OH are important too. A healthy ratio between 2-OH:16α-OH is considered to be two or more whereas a high ratio of 16α-OH:2-OH is associated with unhealthy proliferation of oestrogen sensitive tissues including breast and ovarian tissue.

Supporting phase I liver detoxification promotes the production of 2-OH and decreases the production of 4-OH and 16α-OH. 2-OH and 4-OH may also be oxidised to highly damaging free radicals known as quinones, considered to be the largest health risk associated with oestrogens.

Phase II liver detoxification utilises COMT (catechol O-methyltransferase) to add a methyl group and glutathione S-transferase (GST) to add glutathione (GSH) to the hydroxyoestrone metabolites produced in phase I. Oestrogen may also skip phase I and proceed directly to phase II via glucuronidation or sulfation pathways.

Health hazards of excess oestrogen or unhealthy oestrogen ratios
High levels of circulating oestrogens or unhealthy oestrogen ratios can increase the risk of cellular proliferation, so it’s important that oestrogens are broken down efficiently and effectively for elimination. Certain herbs and nutrients, including Broccoli sprouts, Rosemary, St Mary’s thistle, quercetin and glutathione can all help to support phase I and phase II liver detoxification processes for healthy metabolism of oestrogen in the liver. See Hormone MetabolAid here. 

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