I wrote more extensively on finding and treating root causes for PCOS and estrogen dominance in the linked articles above. For this week’s article, I’m just going to focus on how to support elimination once the excess is there.
Like last week, this one will also be a little heavy on the biochemistry — you are forewarned. ?
First, let’s look at how the body first makes sex hormones, and then how it breaks them down.
The parent of all the sex hormones is cholesterol (so side note: your whole pathway will be suppressed if you’re on statins, which block the production of cholesterol in the first place.) Let’s follow that all the way down to estrogen (estrone: E1, and estradiol: E2).
I wrote here on phase 1 and phase 2 of liver detoxification. Estrogen uses several cytochromes for phase 1 elimination. Phase 2 takes over primarily with COMT, the enzyme in red in the picture there. If you’re familiar with genetic testing, the gene that encodes for this enzyme is one of the famous ones. It’s a methyltransferase, which means it takes a methyl group (a -CH3) from one compound and transfers it to another.
You don’t have to have adequate methyl groups for COMT to do its job; all it’s doing is taking a methyl group that’s already on one compound and moving it to another. But COMT has other jobs besides breaking down estrogen: it’s also the main enzyme responsible for dismantling the catecholamines (dopamine, norepinephrine, and epinephrine) that got their methyl groups from the methylation cycle in the first place (as we discussed here).
So if your COMT enzymes are faster than most, it’ll do a great job at eliminating everything (but you might end up with estrogen and catecholamine deficiency if it’s TOO fast—so depression, probably—if you don’t have a correspondingly quick MTHFR to compensate for it.) If it’s slower than most, you might be more prone to anxiety (especially if your MTHFR is fast) and estrogen dominance.
COMT requires vitamin B6 and magnesium as cofactors to help it to work as efficiently as possible.
Testosterone can either get eliminated via the estrogen pathway (aromitase is the enzyme that converts testosterone into estrogen, and we discussed it in more depth here), or it can go down two different Phase 2 detoxification pathways so that its breakdown products can ultimately be excreted in the urine. In this case, those pathways are sulfation (adding a sulfate group, SO2-4) and glucuronidation (adding glucuronic acid, derived from glucose). The latter also shares some of the estrogen detoxification burden as well.
The sulfur in the sulfate group comes from amino acids that contain sulfur (methionine and cysteine), and also requires molybdenum, B12, folate, magnesium, B6, SAMe, and taurine. Those with sulfur intolerance will have to be careful about consuming too many sulfur-containing amino acids, though. (And if you have a homozygous–two bad copies–COMT gene, you’ll want to be careful with SAMe, as that can speed up the whole methylation cycle and overwhelm an already sluggish COMT!)
Glucuronidation needs magnesium also, and B vitamins. (Calcium D-glucarate provides the precursor to glucuronic acid, and therefore speeds up the process. So it’s quite helpful here.)
In cases of estrogen dominance, it’s helpful to support COMT in addition to finding and dealing with the root issue. That means Vitamin B6 and magnesium.
If testosterone (or androgen) levels are too high, supporting the sulfation and glucuronidation pathways can likewise help. That means sulfur donors (methionine and cysteine, or NAC), methylation support (B6, B12, and folate), magnesium again (it does everything!), and Calcium D-glucarate.
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