BioChem 101

I had a long phone consult with Dr. Veltmann, the biochemist, in New Mexico yesterday. The results of my UEM test are in, and he spent about an hour explaining everything to me. My brain was seriously taxed, but I want to be well-versed before I see my oncologist, Dr. DaSilva, on November 11.

The bottom line (for those who have no desire for the long science story) is that my estrogen profile looks really, really good. All those pills (25 per day--GULP), have had the desired result. Estrogens are like cholesterol numbers--there are good guys and bad guys. My "bad" estrogens are being converted to the "good" protective estrogens at a more efficient rate. By comparing my test results of 2 years ago, when my bad guys were off the chart and my good guys were low and struggling to keep up, we can see that the Sam-E, DIM-PRO, and B-vitamins are facilitating the metabolism of bad to good. Almost all of my good estrogens are now at high levels and my bad ones at low levels.

Since my cancers were ER-positive, fueled by the bad estrogens, this is presumptively great news.

So here's how it works: The body produces Glucocorticoids, which are converted to Androgens.
The primary ones we are concerned with are DHEA which is converted from 17-OH-Pregnenolone to Androstenedione, and the Androstenedione that is converted directly from 17-OH-Progesterone. This is then converted to Estrone (E1) by the enzyme Aromatase.

The oncologist is talking about putting me on an Aromatase Inhibitor, which will disrupt this conversion, effectively wiping out all estrogen production in the body--the good guys along with the bad guys.

But that's not the whole story of estrogen. Estrone (E1) is converted back and forth to Estradiol (E2), (meaning that if the body has an excess of one, it converts some to the other, to keep the two in balance). But E1 also converts in a one-way direction to three other compounds, using the liver's Cytochrome p450 pathways. Two of these three E1 metabolites by themselves are bad guys, 16-alpha-OHE1 and 4-OHE1. The other, 2-OHE1, is a powerful anti-cancer protectant. But the two bad guys can also be converted to good guys: 16-alpha can be transformed to Estriol (E3) and 4-OHE can be changed to 4-MeOE1, if you don't have a mutation on the COMT gene. I have this mutation, a SNIP (single-nucleotide polymorphism) on the COMT and another one on the CYP 1B1 pathway from E1 to 4-OHE1 (which gets converted to the good 4-MeOE1). These mutations are probably what caused or contributed to my estrogens going crazy and fueling my cancers.

According to this latest test, I am close to where I need to be, except for production of E3 from 16-alpha. I have a little too much of bad 16-alpha, and a low level of good E3. The idea that my oncologist understands this biochemistry and will prescribe Estriol to a cancer patient is, shall we say, not bloody likely. So, Dr. Veltmann and I have decided to up my dose of Sam-E, to assist the COMT conversion pathway instead.

The bigger issue is the Aromatase Inhibitor that Dr. DaSilva has mentioned he wants to switch me to. This shuts off the conversion of Androstenedione to Estrone (E1), effectively robbing the body of all the good guys while shutting off all the bad guys. It also leads to a complete and dramatic menopause, more effectively than surgically removing the ovaries. This drug blocks all estrogen production, from all over the body--from fat cells, adrenal glands, etc. After superficially understanding the complicated biochemistry of this system, I fear this drug.

First, I find this explanation of good estrogens versus bad estrogens extremely plausible, given what we know about the delicate balance between LDL/HDL/Triglycerides in regulating cholesterol in the body. Hormonal systems are extremely complex, and I'm pretty sure being in balance is more important than just turning off the estrogen spigot.

Second, I am wimpishly afraid of even more dramatic menopausal symptoms. I'm barely tolerating the truly awful hot flashes, the loss of short-term memory, the insomnia, the night sweats, due to the tamoxifen now. Tamoxifen works in a different way--it sits on the estrogen receptor site of every cell in the body and blocks the entrance gate, but it doesn't interfere with the production or metabolism of estrogens throughout the body.

We are still awaiting the results of the full-month cycle spit test, but the results will be in before my appointment with Dr. DaSilva. Hopefully, I will be able to digest all this information enough to talk to him coherently, and convince him that I'd be better off staying on the tamoxifen.