![]() ![]() This is a key phase II pathway for detoxification of 16α-OH, 2-OH and 4-OH oestrogens. Functional urine testing can provide valuable information on this. 16α-OH and 4-OH are the primary oestrogen metabolites that have been associated with direct genotoxic effects and carcinogenicity. Evidence is accumulating that some oestrogen metabolites may be directly responsible for the initial genetic damage leading to tumours. It has been suggested that those who metabolise a larger proportion of their oestrogen via the 16µ-OH pathway may be at significantly elevated risk of breast cancer compared with those who metabolise proportionally more oestrogen via the 2-OH pathway. In contrast, the 4-OH and 16µ-OH metabolites show persistent oestrogenic activity and promote tissue proliferation. The 2-OH metabolite confers very weak oestrogenic activity and is generally termed the ‘good’ oestrogen. Hydroxylation takes place at different positions on the oestrogen molecule and yields 2-hydroxyoestrone (2-OH), 16µ-hydroxyoestrone (16µ-OH) or 4-hydroxyoestrone (4-OH). Once hydroxylated they can bind to oestrogen receptors and exert their biological activity. This involves the addition of an ‘OH’ group. Once produced, oestrogens are hydroxylated or ‘activated’ via phase I cytochrome P450 enzymes. After menopause, some oestrogen continues to be manufactured by aromatase in body fat. The aromatase enzyme is also found in tissues of endometriosis, fibroids, endometrial and breast cancer, with aromatase expression found highest in or near breast tumour sites. In addition to oestrogen production in ovaries (females) and testes (males) oestrogens are also produced by the aromatisation of androgens in fat cells, skin, bone, brain and other tissues. In very simple terms, this is because they have significant potential to promote the more beneficial routes.īefore we get into the nitty gritty of what each compound does, here’s some context on the aspects of oestrogen processing and metabolism that are relevant to these compounds: And this is where compounds such as sulforaphane, indole-3-carbinol (I3C), di-indolylmethane (DIM) and calcium-d-glucarate can be very useful. Many diet and lifestyle factors influence the way the body handles oestrogens. Some routes are considered more beneficial, and others more harmful to health. To further complicate the picture, there are multiple possible routes through these steps too. Oestrogen production, processing, metabolism and elimination is complex and involves lots of different steps. And once used, they must then be metabolised before they can be eliminated in urine or faeces. Once produced, oestrogens need to be processed or ‘activated’ before they can exert their biological effects. Both males and females produce and need oestrogens, in differing amounts. The term ‘oestrogen’ is used to collectively describe a group of hormones (oestrone (E1), oestradiol (E2) & oestriol (E3)) which have widespread actions throughout the body. In a bid to increase confidence and understanding in this area, here’s a bit of background and a simple overview of each compound, including information on when you might consider recommending in a clinical setting.įirst a bit of background. Unfortunately, confusion reigns supreme over the mechanism of action and potential clinical application of each. Several compounds, including DIM, I3C, sulforaphane and calcium-d-glucarate have the potential to impact this in a beneficial way. The way the body handles oestrogens is an important factor affecting both male and female health.
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