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  4. What about 2-methoxy-E1 low but methylation activity is high? I also see the opposite, 2-methoxy-E1 high and methylation low. What do we want to see with these two markers?

What about 2-methoxy-E1 low but methylation activity is high? I also see the opposite, 2-methoxy-E1 high and methylation low. What do we want to see with these two markers?

Dr. Amy Nett: Okay. So again, what you’re looking for here is not so much the absolute numbers. What you want to see—and for those of who aren’t as familiar with the sex hormone portion of this exam, what we’re talking about here is how estrogens are metabolized and basically excreted. So in this case, you’re talking about estrogen going down the 2-hydroxy pathway, which is the most favorable pathway. So estrogen goes down the 2-hydroxy pathway, and a COMT-dependent enzyme converts to hydroxy-E1 to 2-methoxy-E1 and you get some information about COMT-dependent, that’s catechol-O-methyltransferase, COMT-dependent methylation based on the ratio of 2-hydroxy to 2-methoxy-E1.

So what you’re asking, Laura, is what to do with these, you know, 2-methoxy and 2-hydroxy-E1. It is to some extent the ratio that you want to look at. And remember, when estrogens are lower, you just have a lower amount of estrogens going down these various pathways, those ratios are going to be less useful. The higher the estrogens are, the more helpful those ratios are going to be. But it’s more about what’s the overall methylation activity as opposed to the absolute values of 2-hydroxy and 2-methoxy-E1. So hopefully, that answered some of those questions.

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