Hey guys, I have a fascinating update for you. Please read through this carefully and offer your insights and thoughts below.
Short recap: stopped Letrazole for a few months. Felt fantastic for most of that period, then in the final few weeks could feel the key markers of my condition start to return, namely acute lethargy and unprovoked general anxiety, followed by serious flaccid shrinkage. All for no apparent reason. Usual caveats apply: work stress seems to emphasise this, so does lack of sleep, and for me, sadly, even the smallest amounts of caffeine. I did before and after tests as below:
Total T: 33
Free T: 951 (H)
New test (3-4 months without Let):
Total T: 8.4
Free T: 177 (L)
What struck me here, was that usually my E seemed to inversely correlate with the T i.e. crushing my E lead to raised T and vice versa, which formed the basis of my and my doctor's hypothesis that finasteride has triggered overactivity of my aromatase enzyme. But these results showed very similar estradial levels with very different T levels. I asked me doc about this and he agreed it is very unusual. So I went to go see him, here's a transcript of that meeting (any errors are mine, he talks quickly):
Doc: Based on the mail you've sent, the results are quite interesting, in your case, as you correctly mentioned, the estradial is pretty much the same, yet the T differs substantially. I think in your case, it's not necessarily just about what's happening with the estradial itself, it may about what the body is actually doing to it. So one if the reasons why you might be noticing a better increase (in T) while on an aromatase inhibitor, is because an AI has a dual mechanism of action.
Let me show you (turns to steroid hormone chat) what in your case could be a long-term maintenance therapy. So remember that we discussed, in your case aromatase activity in your body is high and that you super-convert testosterone into estrogen. Aromatase effectively blocks testosterone from estradiol but aromatase also blocks androstenedione which is a precursor to testosterone, into estrone .
Interestingly enough, estrone has been shown to have a very big affinity for binding to the hypothalamic and pituitary tissue in men, as opposed to in women. So the affinity at the bone level, for estrone, remember low estrogen is no good as well, the affinity at the bone level is higher for estradial, the affinity at the brain level is higher for estrone. So what I suspect in your case is that perhaps, when you come off this (AI) you're super-converting it this way (shows androstenedione <> estrone pathway. So 17 beta hydroxysteroid dehydrogenase is an enzyme, but this is not the full picture because there are three different metabolites 2, 4, 16 hydroxyestrone and what the body does to these determines what happens to estrone.
So what I would recommend in your case rather, restart Letrazole, I'll give you a new scritp now, get the estrogen flat first, then once the testosterone increases, reduce the dosage until the estradiol is sitting and 50, 60 odd. When you're sitting at that level, then add something that modulates this (points to androstenedione ndione <> estrone pathway. Then we repeat tests a couple of months later if it's still holding then we ween you off the AI and continue this (the modulator) as maintenance therapy.
Me: Okay, what is the thing that modulates that?
Doc: Indole 3 Carbinol and Diindolylmethane, I3C and something called DIM. This is not a prescription medication, it's a supplement. Now, it's to be used in women.
Me: That seems to be the trend here.
Doc: (laughs) I think in your case it may be a very useful thing. It's made by Solal technologies or Metagenix makes one. The Solal one contains both I3C and DIMM built into it, I'd recommend that one rather. It's called I3Complex. Your estradiol will be lower than females, so just start with one per day. The idea is, I can't measure this. You can't measure it (estrone) like you can estrdial, so they idea is to see what happens with the test when you ween off the AI and you have this (I3C/DIM) as monotherapy, so that we do more frequently. So then what happens is that we effectively update / check the dosage to see what happens with the testosterone. Makes sense?
Me: Makes sense, new insights. That's why I was continuing to do tests, keep a diary and monitor what's happening. Suspected there was more going on behind the scenes.
Doc: I must say, from that perspective its unusual. I've only got two other men that have this type of issue. Fortunately, both have responded well to this type of intervention.
Me: The other guys do they have similar history to me in terms of...
Doc: (Starts nodding)
Doc: Yup, absolutely. Well, let's have a look and see from that perspective. We'll start with the new prescription for the letrozole, see how that goes. The other thing is, Vitamin D, what are you doing there?
Me: I was going to ask you if should get back on that (prescription strength VD), I haven't checked my levels in a while, the tests are getting expensive.
Doc: So remember post winter (winter just ended here) It's not going to be normal, coupled with the fact that your testosterone is low, bone mass is going to be at risk, so it's not a good idea (to stay low). What I would suggest is that I prescribe it for you. Do the pill twice a week (50 000UI twice weekly), do the Letrozole once daily, then in a month's time repeat the estradial test. If its flat then start fiddling around (with the dose + IC3 / DIMM modulation.) there's no point in adding the IC3 now, you want to flatten the estrogen.
Me: Great thanks, have you heard anything else from the matrix, any new insights into this condition?
Doc: There's something called G protein-coupled receptor-type 54, it's seems to be that in those patients that have a predisposition to develop low testosterone, theres seems to be an inactivating mutation where the pituitary and the hypothalamus is very sensitive to tissue estrogen. Now thats the other thing, a lot of these pesticides, plastic bottles etc, work like xenostrogens, we can't actually pick them up on blood tests, disphenalaline (sic??), works like a xenostrogens that we know, that s why women get breast cancer, so we know. And your meats need to be free range, because the other thing is that they inject animals with RDST (?) which is also synthetic estrogen. Drinking water, what do you do there?
Me: I have a filtering system.
Doc: Reverse osmosis or gravity based?
Doc: (shakes head) No good. Gravity based are very good for taking things up to 50 microns out, average hormone is about 2 or 3 microns. The one we use here is a 7 stage RO filter. In your case I'd say be more fussy about the water you drink.
Me: Interesting, I'd done the research but wasn't sure if it was just a lot of fear-mongering or not.
Doc: We did some analysis done with Johannesburg water, which is another thing to remember, the blue drop status we enjoy is purely based on infectivity, so if you see less the 4 ecoli per (x field?) on your tap water you get blue drop status, because you don't develop cholera, it has nothing to do with the purity of the water. Point 2 is that we are a mining town which means that heavy metals are a huge problem. I treat some of the people that work for the mines, and I can tell you that as of the end of this year we will officially have contaminated mine wastage in our drinking supply. We're very fussy about water.
Me: I'm on a forum where guys are asking about flying out here to see you because so few people are taking this seriously overseas.
Doc: Really? That's strange. I thought we (South Africa) would be at the bottom of the list.
Me: What should they do to prepare?
Doc: Do the full set of tests, get a full history together so we can see the timelines etc. (NB!) We had two other guys came to see me thinking it was finasteride and we found prolactin-inducing tumours in the brain. So they did the tests but nobody bothered checking the prolactin. (My note: remember I mentioned at the beginning of all this that the first thing I did after diagnosing Secondary Hypo was the prolactin test, check your prolactin levels guys.)
Me: It's interesting, my best friend also has low T, but is wary of conventional medicine. So he took his results to his homeopath and she never even mentioned the prolactin test, I made him do it as due diligence.
Doc: This is the issue, if it's purely related to that (finasteride) and you find normal prolactin, thats fine. But if your prolactin is sitting at 200, you really can't be entertaining the finasteride as the cause of low testosterone. Then we don't even think about blocking the estrogen or doing anything, we have to get the prolactin down, scan the brain, because there's something growing there. So we've have that sort of experience (making assumptions / treating results alone) and thats what I want to guard against, one has to do this responsibly.
Recaps the treatment, plan of action moving forward:
Let 2.5 daily + VD replacement (50 000UI x2 per week)
In 4-6 weeks time do bloods, see that the E is completely flat and T has recovered.
If so, then we start reducing the Let doses, keep E mid 40-60. If it settles there, then see what the T is sitting at. That's your baseline. Then we add this to it (the I3C / DIM complex). Then every 4 weeks we test the estradiol and testosterone, if its holding then you progressively starting lowering the let dosage and we'll see then what happens.
There are natural alternatives to prescription options as well, Chrysin is a natural AI (My note, have tried this sporadically before). If we can the estradiol stable, then you may not need the letrozole, you can use a combination of chrysin and I3Complex.
Me: I stopped the let and felt great for almost two months afterwards, but the last couple weeks could feel there was a problem, so it seemed to have some kind of protracted effected.
Doc: Remember it will have a tissue benefit because it takes some time to get it in and it takes some time to wash out (My note: this is very, very true, guys that don't experience immediate benefits with let need to wait a month or more in my experience. Medium term usage, i.e. several months, has what has gotten me to the best point). Remember the effect in terms of blocking the estrogen, happens at the tissue level, what you measure is the circulating blood level, but the problem with low T is not circulating, its tissue estrogen and so forth. For obvious reasons I can't get into your tissues to see whats happening there.
So lets start there. In your case, your 17 beta ACD - you probably have that mutation in terms of converting estradiol into estrone (Ed's note: you may remember Doc's previous hypothesis that finasteride can trigger gene mutations that are lying dormant, different people have different potential mutations that may or may not be activated by food, lifestyle, medicine etc)