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Ask patients

I have breast cancer and have heard that you can test what are known as estrogen metabolites. What is it exactly and how do you feel about this test?

Estrogens, the female sex hormones, are important clocks for the menstrual cycle and pregnancies during a woman's fertile years. With the menopause, the production of estrogen continues to decrease in order to be at a low level in the postmenopause (after the menopause). Even if the level of estrogen drops and the hormonal pattern changes, estrogen remains growth-promoting even through menopause. Increasing age is still one of the main risk factors for cancer, especially breast cancer. Early menarche (onset of menstrual bleeding), late menopause and post-menopausal obesity, as well as hormone replacement therapy over a period of more than five years, also significantly increase the likelihood of breast cancer (Colditz 1998, Jefcoate et al. 2000, Reid et al. 1996, Collaborative group on hormonal factors in breast cancer 1997). Many breast tumors have estrogen receptors on their surface. This means that they can grow under the influence of estrogens. Since hormone replacement therapy increases the risk of breast cancer, there is increasing debate as to whether it is better to take a closer look at the natural hormone situation in women. A look at the biosynthesis of estrogens can be helpful here. So let's take a look at which estrogens exist, what their respective effects are and which substances influence the formation and breakdown of these hormones. In addition, it gets a bit scientific: The most important estrogens in humans are estrone (E1), estradiol (E2) and estriol (E3). Estrone can be viewed as a storage form of all estrogens. It has a very mild estrogenic effect as it binds only weakly to the estrogen receptor. Estradiol has the strongest estrogenic effectiveness. Estriol is the main estrogen during pregnancy. Like estrone, estriol also has only a very mild estrogenic effect. Aromatase.

Overweight as a risk factor. The enzyme aromatase is responsible for the synthesis of estrone from androstenedione and estradiol from testosterone. It is a variant of the cytochrome P450 (CYP19A1). The enzyme is located in the ovaries, placenta, brain, bones, skin and subcutaneous fatty tissue. This CYP19A1 enzyme is of particular importance in very overweight women: aromatase can be present in extensive adipose tissue in such large quantities that it significantly influences the hormone levels of those affected in younger years and can lead to fertility disorders. During the menopause, a body weight that is too high can initially have a weakening or delaying effect on the menopausal symptoms. The risk of breast cancer, on the other hand, can increase significantly. While the enzyme aromatase is only found in small quantities in the liver, the further conversion of the estrogens in the liver to breakdown products (the so-called estrogen metabolites) plays an important role in the effect of the estrogens. Because the resulting estrogen metabolites can have protective or cancer-promoting properties. The ratio of protective and damaging breakdown products to one another therefore provides an indication of the risk of breast cancer. Hydrolyzed estrogens. In the liver, various breakdown products, so-called hydroxylated oestrogens, are produced in two conversion steps: 2-hydroxy-, 4-hydroxy- or 16α-hydroxy-oestrone. The 2-OH metabolites protect against cancer, while the 4-hydroxy-estrone and 16-hydroxy-estrone have a strong estrogen and thus carcinogenic effect.

Complex interrelationships. Conversely, we know from studies that with a high rate of hydroxylation to 2-hydroxy-estrone, estrogen-dependent tumors occur less frequently. The relationships in hormone metabolism are really complex. 2-Hydroxy- and 4-Hydroxyestrones can be metabolized to quinones, which under certain circumstances react directly with the DNA. COMT. The two-stage degradation (first hydroxylation, then methylation) is mediated by the enzyme catechol-O-methyltransferase (COMT). COMT requires magnesium, potassium and S-adenosylmethionine (SAM) as cofactors. The enzyme COMT is also required for the breakdown of stress hormones. This explains the relationship between stress, hormonal balance and cancer risk: the more stress hormones that have to be detoxified by COMT-mediated methylation, the less COMT is left for estrogen conversion. The methylation activity of COMT also decreases in obese women. The intermediate products can then accumulate up to critical concentrations. Diet and Lifestyle. By determining the metabolites and the 2- / 16α-estrogen ratio, statements can be made about changes in the estrogen metabolism.

Influence of lifestyle. However, the individual 2- / 16α-estrogen ratio of a woman is not exclusively genetically predetermined. A variety of dietary measures and lifestyle factors can influence the 2-hydroxylation of estrogens and thus cause an increase in the 2- / 16α-OH-E1 ratio. The activity of the enzyme CYP1A1, which degrades to 2-OH, can be improved by the natural substance indole-3-carbinol (I3C). Flax seeds and omega-3 fatty acids have a positive effect on the 2- / 16α-OH-E1 ratio. In addition, we generally recommend breast cancer patients to exercise regularly, to lose weight in a sensible way if they are overweight and to limit their alcohol consumption. Because alcohol hinders the breakdown of estrogens in the liver. If a poor methylation activity of the COMT is detected in the laboratory, an improvement can be achieved through the use of certain micronutrients. The main focus is on the cofactor magnesium, but also on vitamins B2 and B3. Resveratrols (e.g. from blue grapes and raspberries) block the oxidation of catechol estrogens to quinones and can thus have an indirect cancer-inhibiting effect.

Prevention. Estrogens and their breakdown products are excreted via the kidneys and the biliary tract. This results in further prevention options: The patients need sufficient fluids. Furthermore, the diet should contain an appropriate amount of fats (and possibly bitter substances) in order to stimulate the flow of bile. Fiber is also important. They bind the hormones and their breakdown products in the intestine. Women whose first-degree relatives (mother, sister) have been diagnosed with breast cancer, who have been taking the pill or hormone replacement supplements for a long period of time, or who are overweight, benefit most from these recommendations. Either way, the measures mentioned have a preventive effect even without additional examinations. Good to know. Incidentally, the costs for determining the estrogen metabolites (Estronex) in the urine are manageable. They are between 50 and 70 euros. Please note before performing this test: The assessment of breast cancer risk using the Estrogen-Metamomentum Bolite is only useful in postmenopausal women. There are a few reports in the literature that a connection can also be established before the menopause. However, the data situation is not clear. In larger studies, no association was found in premenopausal study participants.