***Hi, Aquariusgirl.
***My responses are at the asterisks below:
rich
wouldn't you have to show that these snps occur at a higher rate in women with cfs than women in general to prove yr argument?
***Yes, and it would also be helpful to show that they occur at a higher rate in women with CFS than in men with CFS. Since these things have not been shown (yet!), this is a hypothesis, not something that can be considered scientifically proven.
so many of the snps implicated in this disease are so common, that it makes me wonder.
***Right.
i know the argument is that it's the combination of all these snps...clustered around certain pathways. that add up to a genetic predisposition to the illness ..but in the absence of comparative genome-wide studies, it's kind of a hard sell isn't it?
***Yep.
how many of the panels you have mentioned have you seen from women that don't have cfs.
***Zero. People have to have a reason to plunk down the coins, and the Detoxigenomic profile isn't cheap. Also, I study cases only of people who either have CFS or think they might. Maybe as time goes on the cost of looking at polymorphisms, such as by the major providers like 23andme, will get low enough that more people will have them characterized. There's probably enough data out there now to evaluate the prevalence of this combination of SNPs, but I don't think I would have access to it.
Does genovations share that info? Probably not, right?
***No, they don't. I spoke to the lab director about that when I was writing the paper in 2006-2007.
Having said that, wld your hypothesis explain why so many women with cfs feel worse when they are premenstrual?
***I'm not sure. That's one of the two times in the cycle when the estradiol level is dropping (and the only time when both estradiol and progesterone levels are dropping simultaneously). But there is also a big drop in estradiol level at midcycle, just after ovulation (progesterone is rising at that time), and I don't think women with CFS feel worse at that time, do they? So I think progesterone comes into the picture here.
I know that progesterone has sometimes been called the "feel good" hormone for women.
***One question to which I have not been able to find the answer is whether the changes in estradiol level in the cycle are purely the result of changes in its rate of secretion by the ovaries, or are there also changes in the rate it is broken down (metabolized), such as by varying the gene expression of the detox enzymes that metabolize it? If the latter is true, and if the rate of metabolism of estrogen increases premenstrually, then I think I could make a case for this set of polymorphisms being responsible for many female PWCs feeling worse premenstrually, because there would be a higher contribution to oxidative stress at that time. Otherwise, I don't think this would explain feeling worse premenstrually.
***Not being a woman myself, I have no clue how this feels, of course. My impression is that PMS is an issue for many women who don't have CFS, but I don't know whether PMS in a woman who doesn't have CFS bears any resemblance to what goes on premenstrually in women who have CFS. Maybe you and/or some of the other women here can enlighten me a little about how it feels in these two situations
-)!
This is probably like trying to describe colors to a person who is colorblind!
***I've done a fair amount of digging in the literature about this, and have not found anything. It may not be known. There appear to be a few mysteries remaining about the menstrual cycle and what causes what there. I would actually like to understand this whole area better. I don't think the interactions of the HPA axis dysfunction and the reproductive steroid hormone cycling in women, especially when menopause starts coming into the picture, are very well understood in CFS. This is pretty complex even when CFS is not part of the picture.
***I think that the late Dr. John Lee made a big advance when he emphasized the prevalence and importance of estrogen dominance over progesterone in many women, and I think Sabre Sciences has the right idea when they emphasize working on the low cortisol problem before boosting progesterone, because it will be diverted to making cortisol, but I think a lot of this is still a "black box." (I guess I should explain that that is a term from textbook problems in electronic engineering. The idea is that you are given a "black box" with a couple of electrical terminals on it, and it is specified that certain types of measurements give certain types of results. The problem is then to explain from these data what is inside the "black box." I'm suggesting that there is still a lot unknown about the menstrual cycle and how it works at a fundamental level, let alone what goes awry.)
***Best regards,
***Rich
