Estrogen Metabolism
Estrogen: 'Bad Girl' or 'Good Girl'? Estrogen and its implication on our health has been a subject on women's minds ever since the news came out a few years ago about the risks of hormone (estrogen) replacement therapy (HRT). Large studies showed increases in heart disease, cancers, overall mortality, and now even dementia in HRT users. But how can that be? Estrogen has beneficial effects on our health including protecting us from heart disease. The answer probably is multifactorial, but more and more interest is being shown in the effects of the active metabolites of estrogen.
The term 'estrogen' is used collectively for a group of female hormones constructed on a cholesterol molecule base. In the non-pregnant human these are mainly Estrone (E-1) and Estradiol (E-2). During pregnancy the placenta makes Estriol (E-3). But in nature, there are many different estrogens, over 100 of which are found in the equine (horse) estrogens found in HRT and other medications.
Hormones are chemical messengers that cause profound changes within their target cells. The way the endocrine system broadcasts its hormonal messages is like a radio broadcast. It is sent out to all cells, but only the cells with the specific receptors (radios) get the message. The receptor is where the hormone docks and once docked it manifests its effect on the cell.
Excess circulating hormone is cleared from the body via metabolism to a disposable form, the metabolite. The first step with estrogens is hydroxylation, followed by methylation, then excretion into the urine or bile and elimination. The importance of this is that the hydroxylation can occur at three different sites on the estrogen molecule, and since these hydroxylated estrogens (estrogen metabolites) also have biologic activity, it is important at which site it occurs. Studies have shown that women who hydroxylate their estrogens on the 2nd carbon have less cancer than those who do so on carbon No. 4 or No.16. The 2-hydroxyl to 16- hydroxyl ratio (2-H/16-H) is how this is expressed; and the higher the ratio, the better for the lady.
What determines how the estrogen will be metabolized? That's what isn't known. Of course a good bet is: your genes. But why would genes that metabolize it in a way that is detrimental to longevity be selected for? Therefore environment, nutrition, and lifestyle are suspected to play a major role.
Cruciferous vegetables (and undoubtedly others as well) contain phytonutrients that increase the 2-H/16-H ratio. Steps further down the metabolic pathway are also nutrition-dependent and these steps effect the make up of the metabolic profile that includes quinones (carcinogenic) and neurotransmitters (catecholamines & serotonins) that have an effect on mood and personality. Lycopenes, flavonoids, isoflavones, lignans, and catechins have also been shown to influence estrogen metabolic pathways.
Sound empiric advice then, since you can't change your genes, is to have as varied and nutritious a diet as possible to maximize your 2-H/16-H ratio AND when you reach that age where you may need to supplement your naturally produced estrogen, consider doing so with those estrogens (E-1 and E-2) that your body naturally produces.
The term 'estrogen' is used collectively for a group of female hormones constructed on a cholesterol molecule base. In the non-pregnant human these are mainly Estrone (E-1) and Estradiol (E-2). During pregnancy the placenta makes Estriol (E-3). But in nature, there are many different estrogens, over 100 of which are found in the equine (horse) estrogens found in HRT and other medications.
Hormones are chemical messengers that cause profound changes within their target cells. The way the endocrine system broadcasts its hormonal messages is like a radio broadcast. It is sent out to all cells, but only the cells with the specific receptors (radios) get the message. The receptor is where the hormone docks and once docked it manifests its effect on the cell.
Excess circulating hormone is cleared from the body via metabolism to a disposable form, the metabolite. The first step with estrogens is hydroxylation, followed by methylation, then excretion into the urine or bile and elimination. The importance of this is that the hydroxylation can occur at three different sites on the estrogen molecule, and since these hydroxylated estrogens (estrogen metabolites) also have biologic activity, it is important at which site it occurs. Studies have shown that women who hydroxylate their estrogens on the 2nd carbon have less cancer than those who do so on carbon No. 4 or No.16. The 2-hydroxyl to 16- hydroxyl ratio (2-H/16-H) is how this is expressed; and the higher the ratio, the better for the lady.
What determines how the estrogen will be metabolized? That's what isn't known. Of course a good bet is: your genes. But why would genes that metabolize it in a way that is detrimental to longevity be selected for? Therefore environment, nutrition, and lifestyle are suspected to play a major role.
Cruciferous vegetables (and undoubtedly others as well) contain phytonutrients that increase the 2-H/16-H ratio. Steps further down the metabolic pathway are also nutrition-dependent and these steps effect the make up of the metabolic profile that includes quinones (carcinogenic) and neurotransmitters (catecholamines & serotonins) that have an effect on mood and personality. Lycopenes, flavonoids, isoflavones, lignans, and catechins have also been shown to influence estrogen metabolic pathways.
Sound empiric advice then, since you can't change your genes, is to have as varied and nutritious a diet as possible to maximize your 2-H/16-H ratio AND when you reach that age where you may need to supplement your naturally produced estrogen, consider doing so with those estrogens (E-1 and E-2) that your body naturally produces.
posted by Dr. Lorna's Coaching Blog at Friday, February 16, 2007
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