High estrogens / SHBG

[Castaneda]

This will be my first post here.

I have suffered symptoms of low T for quite some time, and I have been consulting with various hormone experts trying to understand my steroid hormone metabolism more deeply. I won't name names, but I keep hearing "there is nothing you can do about this, and you need TRT". I haven't jumped to that conclusion yet. Let me explain why:

I have done several tests, with and without precursors like DHEA and Pregnenolone. Without them, Life Extension labs show the following values (we'll call this my baseline):

Testosterone, Serum 672 ng/dL (264-916)
Free Testosterone (Direct) 9.9 pg/mL (6.8-21.5)

DHT 55 ng/DL (30-85)
LH 3.0 mIU/mL (1.7-8.6)
FSH 2.5 mIU/mL (1.5-12.4)
DHEA-S 186.6 ug/dL (102.6-416.3)

Estradiol 9.5 pg/mL (7.6-42.6)
Estrogens, Total 115 pg/mL (40-115)
SHBG 88.6 nmol/L (16.5-55.9)

I read this to mean my testosterone and especially E2 are low because of insufficient DHEA (possible adrenal stress). What has me puzzled are the total estrogens (top of range) and extremely high SHBG. We know that SHBG goes up, generally, under two circumstances: high estrogen and high thyroid hormones. The latter is not a problem (with high RT3 and lower than optimal T3, 25.2 and 2.9, respectively). TSH is 3.1 (I know). So that leaves me to believe SHBG is going up because of high estrone.

I have tried to fix this problem by taking extra DHEA, but it just exacerbates the problem. The more DHEA, the more estrone goes up and T and E2 remain more or less the same. I have also tried Pregnenolone and DHEA together, and while this does seem to raise T and E2, E1 continues to overflow like a waterfall. DIM just lowers E2 further, creating symptoms.

Not long ago, I decided to try Pregnenolone only at ~10mg, 3x a day and then did a 24-hour urine Rhein Lab metabolite panel (attached). You will see moderately low T and E2 (as espected), in range E1, extremely high 2OH/16OH ratio (also not surprising) and DHEA totally off the charts at 2260. Pregnanediol is also extraordinarily high, but that's typical with Preg.

No matter what I do, my body just wants to take DHEA and aromatize it to E1 (via Androstenedione), with T and E2 suffering. I keep coming back to poor 17-beta HSD expression. The other thought I had, and my reason for posting here, is... could it be that because DHEA is aromatizing to heavily ot E1 that it is bringing up SHBG and, in turn, binding to T and E2, pushing them down? In other words --- E1 is going out of control, liver pumps out SHBG to handle it, and it ends up taking otherwise good T / E2 levels with it.

That last idea was behind my last experiment inspired from a few posts over on the Ray Peat forum. I decided to try putting a 5mg/5mg solution of Pregnenolone and DHEA directly on the scrotum two times a day in combination with 5mg of Androsterone (which is supposedly able to inhibit aromatase with 90% efficiency). That's a total of 10mg Preg, 10mg DHEA and 10mg Androsterone per day. Initially, I felt quite well, but about a week into it, I started getting tendonitis and muscle aches to the point of feeling like an old man. Just a guess: androsterone was probably bringing down estrone but, again ... E2 coming too low as well. That's nearly as dangerous as high E2.

Regardless, libido, motivation, and energy are in the toilet, no matter what I do.

The last doc I spoke to said the only way to overcome that high SHBG is directly with testosterone gel. I'm not opposed to the idea, but I want to get some additional input from the forum here to see if anyone else has seen this pattern (before I go off and shrink my testicles to peanuts). When you inhibit aromatase, it's rather indiscriminate (as far as I understand). You are pulling back the reigns on both Androstenedione > Estrone and Testosterone > E2. The former is the problem, me probably needing more of the latter.

If I were to take just straight HCG, that would bypass the whole DHEA conversion problem, but my DHEA without any precursors was low, as shown on the LE lab above. It's a real Catch 22 and I can't help but think I'm missing something here.

Any ideas?

 

[Gman86]

Does the DHEA range really go up to 2486? That’s an extremely odd range if that’s true. What dose of DHEA were you taking when it came back high? It seems impossible that your DHEA was actually 2260. I’m pretty sure that’s the wrong test for DHEA anyways. The gold standard, as far as I know, is to test for DHEA-S. Looks like you just had the regular DHEA test done. You did, however, have the correct test done when your DHEA was 186.6.

And I’m not sure that those are the only two reasons SHBG can be high. Mine has always been high, and pre TRT my E2 always sat around low to mid 20’s. My thyroid is also not very high. I have a low TSH, low reverse T3, low total T4 and T3, and a free T3 of 3.4 (2.3-4.2).

What’s your hesitation with starting TRT? If I were you, I would personally get on TRT. Even with supplementing with DHEA and pregnenolone, it’s hard to believe that you’re going to overcome that very high SHBG and ever have a decent free testosterone from just those two supplements alone. I would also address your thyroid and low DHEA level.

 

[Vince]

If it was me, I would first take care of my thyroid issues. Can you post your TSH, free T4, free T3, reverse T3, and both antibodies along with the ranges. I wonder if low dose clomid would be of any help. You could try 12.5 mg of clomid twice a week or every other day.

 

[Vince Carter]

This will be my first post here.

I have suffered symptoms of low T for quite some time, and I have been consulting with various hormone experts trying to understand my steroid hormone metabolism more deeply. I won't name names, but I keep hearing "there is nothing you can do about this, and you need TRT". I haven't jumped to that conclusion yet. Let me explain why:

I have done several tests, with and without precursors like DHEA and Pregnenolone. Without them, Life Extension labs show the following values (we'll call this my baseline):

Testosterone, Serum 672 ng/dL (264-916)
Free Testosterone (Direct) 9.9 pg/mL (6.8-21.5)

DHT 55 ng/DL (30-85)
LH 3.0 mIU/mL (1.7-8.6)
FSH 2.5 mIU/mL (1.5-12.4)
DHEA-S 186.6 ug/dL (102.6-416.3)

Estradiol 9.5 pg/mL (7.6-42.6)
Estrogens, Total 115 pg/mL (40-115)
SHBG 88.6 nmol/L (16.5-55.9)

I read this to mean my testosterone and especially E2 are low because of insufficient DHEA (possible adrenal stress). What has me puzzled are the total estrogens (top of range) and extremely high SHBG. We know that SHBG goes up, generally, under two circumstances: high estrogen and high thyroid hormones. The latter is not a problem (with high RT3 and lower than optimal T3, 25.2 and 2.9, respectively). TSH is 3.1 (I know). So that leaves me to believe SHBG is going up because of high estrone.

I have tried to fix this problem by taking extra DHEA, but it just exacerbates the problem. The more DHEA, the more estrone goes up and T and E2 remain more or less the same. I have also tried Pregnenolone and DHEA together, and while this does seem to raise T and E2, E1 continues to overflow like a waterfall. DIM just lowers E2 further, creating symptoms.

Not long ago, I decided to try Pregnenolone only at ~10mg, 3x a day and then did a 24-hour urine Rhein Lab metabolite panel (attached). You will see moderately low T and E2 (as espected), in range E1, extremely high 2OH/16OH ratio (also not surprising) and DHEA totally off the charts at 2260. Pregnanediol is also extraordinarily high, but that's typical with Preg.

No matter what I do, my body just wants to take DHEA and aromatize it to E1 (via Androstenedione), with T and E2 suffering. I keep coming back to poor 17-beta HSD expression. The other thought I had, and my reason for posting here, is... could it be that because DHEA is aromatizing to heavily ot E1 that it is bringing up SHBG and, in turn, binding to T and E2, pushing them down? In other words --- E1 is going out of control, liver pumps out SHBG to handle it, and it ends up taking otherwise good T / E2 levels with it.

That last idea was behind my last experiment inspired from a few posts over on the Ray Peat forum. I decided to try putting a 5mg/5mg solution of Pregnenolone and DHEA directly on the scrotum two times a day in combination with 5mg of Androsterone (which is supposedly able to inhibit aromatase with 90% efficiency). That's a total of 10mg Preg, 10mg DHEA and 10mg Androsterone per day. Initially, I felt quite well, but about a week into it, I started getting tendonitis and muscle aches to the point of feeling like an old man. Just a guess: androsterone was probably bringing down estrone but, again ... E2 coming too low as well. That's nearly as dangerous as high E2.

Regardless, libido, motivation, and energy are in the toilet, no matter what I do.

The last doc I spoke to said the only way to overcome that high SHBG is directly with testosterone gel. I'm not opposed to the idea, but I want to get some additional input from the forum here to see if anyone else has seen this pattern (before I go off and shrink my testicles to peanuts). When you inhibit aromatase, it's rather indiscriminate (as far as I understand). You are pulling back the reigns on both Androstenedione > Estrone and Testosterone > E2. The former is the problem, me probably needing more of the latter.

If I were to take just straight HCG, that would bypass the whole DHEA conversion problem, but my DHEA without any precursors was low, as shown on the LE lab above. It's a real Catch 22 and I can't help but think I'm missing something here.


Any ideas?

I really don't see that you're on this like you think you are, you try to sound smart but you're just so far off base on all of it that I don't know where to start but will say you're using the wrong Estrogen testing. Given how you've typed that all out I doubt any one is going to convince you otherwise.

 

[Castaneda]

Does the DHEA range really go up to 2486? That’s an extremely odd range if that’s true. What dose of DHEA were you taking when it came back high? It seems impossible that your DHEA was actually 2260. I’m pretty sure that’s the wrong test for DHEA anyways. The gold standard, as far as I know, is to test for DHEA-S. Looks like you just had the regular DHEA test done. You did, however, have the correct test done when your DHEA was 186.6.

And I’m not sure that those are the only two reasons SHBG can be high. Mine has always been high, and pre TRT my E2 always sat around low to mid 20’s. My thyroid is also not very high. I have a low TSH, low reverse T3, low total T4 and T3, and a free T3 of 3.4 (2.3-4.2).

What’s your hesitation with starting TRT? If I were you, I would personally get on TRT. Even with supplementing with DHEA and pregnenolone, it’s hard to believe that you’re going to overcome that very high SHBG and ever have a decent free testosterone from just those two supplements alone. I would also address your thyroid and low DHEA level.

Thank you for the input.

My apologies if I wasn't clear about it, but I did measure DHEA-S (blood serum) while taking absolutely nothing, and it came out to 186.6 ug/dL (102.6-416.3), near the bottom of the range. The 2486 shown in the graphic is from a 24-hour urine metabolite test (Rhein labs). It has different ranges than blood serum. While doing the Rhein, I was on 30mg of Pregnenolone and **no DHEA**, so my interpretation was that Pregnenolone was converting to DHEA. This makes sense, seeing that the cortisol / cortisone were low end of range. If cortisol were high, then there would be less 17-OH-Pregnenolone available for DHEA production.

My hesitation with starting TRT is because my total testosterone still appears to be salvageable. I don't want to shut-down endogenous production if there is the possibility that I can resolve the estrogen imbalance problem. As a matter of fact, I have had windows of high libido and drive using the DHEA / Pregnenolone / Androsterone combination on the scrotum, but this estrone problem is always stepping in.

Silently, I know there is no way around this without targeted gene therapy or other medications which haven't been developed yet. The majority of interventions out there are still quite primitive. I actually work with a lab that performs peptide research, so I can say there are a lot of people looking at this problem. But until that goes primetime, I have to pull all the shots before jumping off a cliff with TRT. I am not comfortable with the vulnerability of being in a situation where, if ever the androgen source dries up (via FDA regulations or God knows what else), I don't want to be left with the T levels of 13-year old girl. Call me paranoid.

 

[Castaneda]

I really don't see that you're on this like you think you are, you try to sound smart but you're just so far off base on all of it that I don't know where to start but will say you're using the wrong Estrogen testing. Given how you've typed that all out I doubt any one is going to convince you otherwise.

Please help me understand where I am off base. I happen to be a clinician, so while my understanding may not be optimal, I've looked at enough labs (both my own and others) to see patterns.

The estradiol listed above is the (inaccurate) Roche ECLIA method that Life Extension uses. I have followed up with "sensitive assays" (LabCorp and Quest), and they all show numbers below 10. Tendonitis and muscle pain are some of the symptoms of low estradiol -- not to go off on a tangent, but here's a good introduction to this subject:

https://www.sciencedirect.com/science/article/pii/S0960076017301590

I have gotten into this problem by using DIM, aromatase inhibitors, and lately -- androsterone. It lowers my already low estradiol, causing the aforementioned issues.

So let's make this conversation useful, if possible, and guide each other. I'm not holding onto any dogma here. I just haven't found anyone that understands these pathways very well and is able to navigate this problem. Yes, I get it: using TRT is going to overcome the high SHBG and resolve the problems of functionally low T. It's low hanging fruit. As I have mentioned above, I want to explore other options before making that leap.

If none are available, simply state so. I'm open to ideas one way or the other.

 

[Castaneda]

If it was me, I would first take care of my thyroid issues. Can you post your TSH, free T4, free T3, reverse T3, and both antibodies along with the ranges. I wonder if low dose clomid would be of any help. You could try 12.5 mg of clomid twice a week or every other day.

The thyroid problem is rather complicated. I have some unique immunological issues and multiple viral infections that I'm constantly suppressing with diet and lifestyle. There is the problem of inadequate secretory IgA levels (confirmed on labs), which is easy to fix in the gut, but not so much on other surfaces like the lungs (I am prone to asthma).

So I get some relief with thyroid when viruses are quiet and diet is clean, but in winter-time, NDT doesn't cut it because there tends to be too much T4 in it and it ends up converting too heavily to RT3. I have turned to liothyronine, sublingual drops, as needed.

On another note, you might find it interesting that I was able to table the T3 drops when I started applying androsterone to the scrotum. At first, I couldn't figure out why, then I discovered it's a thyroid mimetic:

THE EFFECT OF ATROMID, AN ORALLY ACTIVE ANDROSTERONE ON SERUM LIPIDS IN NORMAL, HYPERCHOLESTEROLAEMIC AND HYPERLIPAEMIC SUBJECTS. - PubMed - NCBI

The androsterone-etiocholanolone excretion ratio in hyper- and hypothyroidism. - PubMed - NCBI

As I stated above, it helps thyroid but ends up lowering my estradiol even further (and it's already low according to several sensitive assays). I would be concerned about using Clomid or any other estrogen receptor blocker, as that would just aggravate the low estradiol problem, which as of right now, continues to be an issue.

 

[Castaneda]

I failed to mention that I have been looking at HCG monotherapy. I have heard that it may not be as effective at overcoming the high SHBG, but I am still sticking to the idea that estrone is pushing that up.

 

[Sean Mosher]

I don't know how you are going to overcome that super high SHBG without exogenous testosterone.
Based on your labs you could always give Clomid a run as well, but will need a solid doc who understands how to prescribe/use it.

They are doing some very interesting things with peptides.
Will be great to see what the future has in store there no doubt.

I can understand your fears on Testosterone being heavily monitored but it isn't going anywhere.
We will always have access to it.

 

[Castaneda]

I don't know how you are going to overcome that super high SHBG without exogenous testosterone.
Based on your labs you could always give Clomid a run as well, but will need a solid doc who understands how to prescribe/use it.

They are doing some very interesting things with peptides.
Will be great to see what the future has in store there no doubt.

I can understand your fears on Testosterone being heavily monitored but it isn't going anywhere.
We will always have access to it.

The anti-aging community puts optimal male estrogen at 20-30, though it's very individual. Some men feel awful with 20 while others thrive at that level. Mine is at 9 (using the sensitive assay), and I am concerned that Clomid could cause issues from blocking the effects of what little estrogen I have. And while estrone has lower binding affinity for estrogen receptors, just having a shit-load of it around would be enough to increase SHBG and take some T and E2 along with it. At least that's the theory I've been playing with.

Interesting side note --- I have been able to get transient surges of T (and libido) by putting an 850nm red LED light array on the testes. Nobody knows the long-term affects of this approach, but it's apparently stimulating mitochondria in Leydig cells. My concern would be potential for testicular cancer. Anyway, the reason I mention LLLT is because it looks like it functionally has the same effect as LH on Leydig cells, which is what HCG monotherapy would induce.

I could care less about spermatogenesis, as I have three kids. My baby-making days are done and over. This study would seem to indicate HCG could potentially lower SHBG (and raise free T and E2 which is what I need):

Sex hormone-binding globulin changes with androgen replacement. - PubMed - NCBI

 

[PhilM7]

The anti-aging community puts optimal male estrogen at 20-30, though it's very individual. Some men feel awful with 20 while others thrive at that level. Mine is at 9 (using the sensitive assay), and I am concerned that Clomid could cause issues from blocking the effects of what little estrogen I have. And while estrone has lower binding affinity for estrogen receptors, just having a shit-load of it around would be enough to increase SHBG and take some T and E2 along with it. At least that's the theory I've been playing with.

Interesting side note --- I have been able to get transient surges of T (and libido) by putting an 850nm red LED light array on the testes. Nobody knows the long-term affects of this approach, but it's apparently stimulating mitochondria in Leydig cells. My concern would be potential for testicular cancer. Anyway, the reason I mention LLLT is because it looks like it functionally has the same effect as LH on Leydig cells, which is what HCG monotherapy would induce.

I could care less about spermatogenesis, as I have three kids. My baby-making days are done and over. This study would seem to indicate HCG could potentially lower SHBG (and raise free T and E2 which is what I need):

Sex hormone-binding globulin changes with androgen replacement. - PubMed - NCBI

Castaneda, how long do you expose your testes to the red light? I had never heard of that before, but I just googled it and see that they recommend at 670 nm red light wavelength. That is very interesting.

 

[Castaneda]

Castaneda, how long do you expose your testes to the red light? I had never heard of that before, but I just googled it and see that they recommend at 670 nm red light wavelength. That is very interesting.

Back while I was doing that, I was going for about 5 minutes, 3x a week, never two days in a row. That seemed to be enough to stimulate T production. These days, my SHBG is so high, it no longer works.

 

[Castaneda]

I've been away for a while researching options. Ultimately, I decided to start testosterone therapy, but it has only made matters worse. Let me explain:

I started with IM injections of cypionate, 100mg 2x a week. After frequently hitting nerves in all the recommended injection sites and generally feeling much worse post-injection (lower energy, brain fog, low mood, etc.), I decided to switch to a 200mg liposomal cream.

The first few days on the liposomal cream, my dopamine and libido just shot up. I felt great again (finally). That tapered out after a week and gradually changed to lower energy, a complete obliteration of libido, and fairly severe depression. The first 3 weeks, I was using a TopiClick (3 clicks, twice a day on the inner thigh). I discussed the symptoms with the doctor, and his comment was "that's not typical -- but let's give it another 2-3 weeks and test to see where things are at". At that point, he suggested switching from inner thigh application to directly on the scrotum.

Fast forward to a week ago, when I had been putting 1 gram of 200mg liposomal cypionate cream on the testes twice a day. I went in for a blood lab about 4-5 hours post morning application. Here is what came out of that:

Hemoglobin: 16.2 g/dl (13-17)
Hematocrit: 45.9% (37-49)
Platelets: 182 (130-400)
CBC: Normal except for slightly elevated eosinophils
Estradiol 39.1 pg/ml (<=60.7)
Testosterone: 1082 ng/dl (300-890)
SHBG: 50.4 nmol/l (16.5-55.9)
Calc Free T: 204.5 pg/ml (47-244)

So from a free T point of view, I'm in the zone. SHBG has come down since the last lab (it was 66), and estradiol has come up, over the "optimal" range of 20-30. Before starting therapy, it showed 26.

So my symptoms are telling me I am still low T. I feel no energy, limited ability to get an erection or keep it, low libido, and generally depressed. The doc reviewed these labs and responded, "perhaps T therapy is not for you". I'll reserve my lack of enthusiasm for this statement.

Where to go from here? The doc keeps pressing me saying this is a high cortisol problem and that cortisol is blocking the androgen receptors-- but if I take one of the cortisol modulating substances (Seriphos, Ashwagandha, Rhodiola, etc.) it makes my energy deficit worse.

Has anyone else seen labs like this with subjective feelings of low T? SHBG does seem to be coming down, but isn't that estradiol level a problem? I mentioned it to the doc and he said "estradiol protects against atherosclerosis and cardiovascular disease, similar to women". Terrific. And we now have Jay Cambell et. al. jumping on that bandwagon saying aromatase inhibitors are dangerous and to work on improving insulin sensitivity, reducing adipose tissue, etc. All good recommendations --- as I do have more adipose fat than I need (which is likely the culprit in higher estradiol levels). But I'm in a Catch 22. In order to lose that fat, I need to exercise, and I have hardly enough energy to walk around the block, let alone lift some weights. It's that bad. I feel just awful.

The doc ended up giving me .5mg Arimidex, 2x a week as an experiment (for 1 month) to see if the high SHBG could be increasing estrogen's effects. I don't have puffy nipples or emotional ups / downs --- just feeling flat, no energy, and no libido, which (in my opinion, at least), is just as bad, if not worse.

The question in my mind is --- how much estrogen is too much estrogen? I have low tolerance for these blanket statements. We can all agree that too little estrogen is bad, but there are ample studies showing too much can lead to prostate cancer and clotting issues. Dr. Crisler recently had a heart attack not a week after he suddenly stopped using Arimidex. I'm not jumping to any conclusions here, but it makes you think --- his first heart attack was due to a blood clot. What did his E2 levels look like? Last I spoke with him, he didn't feel it was necessary to look at PT / PTT in men with stroke risk. This raised a red flag for me --- as does the newly popular rhetoric that we should all ditch the idea of inhibiting aromatase. Too much estrogen is a bad thing, regardless of how many studies prove it prevents atherosclerosis. Just an example:

Circulating estradiol and mortality in men with systolic chronic heart failure. - PubMed - NCBI

Yes, an observational study, but there are many others.

Consider this. 39.1 E2 may not be high enough to produce symptoms, but with high SHBG, we have a changed playing field. SHBG binds to androgens with higher affinity, and when you have a lot of it running around, it's going to hug onto T and DHT much tighter while letting E2 have a free ride. That 39.1 E2, in that circumstance, could behave like much higher E2. At least that's how I'm feeling. This is partly why going on subjective feelings is more important than a lab number.

So that's where I'm at. Thanks for listening. I'm going to trial the Arimidex and then test again in 1 month to see where E2 is sitting. Hopefully, during that time, I'll have some change in subjective well-being, similar to the way I felt the first few days of liposomal cream. Then I can get intermittent fasting in gear along with some light weight training --- to turn the tide.

In the meantime, if any of you have stories to share or tips, let me know. And yes, I'm looking after my thyroid. I have chronically high RT3 and cannot take NDT (because the T4 in the grains converts almost instantly to RT3). My free T4 and T3 levels look good on labs with a TSH over 3. So I've been flushing out RT3 with straight Cytomel (administered as sublingual drops in a tincture, 3mcg, 4x a day). Speaking of which, off to take my last liothyronine dose of the day.

Thanks again for reading.

 

[Systemlord]

Your Free T percentage is only 1.91 %, I can tell you my symptoms of low testosterone disappear when I reach 2.5% Free T, by then Free T is 20.8 (range 6.8-21.5). It is known normally men have a Free T percentage of 2-3 percent.

Injectable cypionate testosterone produces spikes unlike creams, large spikes (excess androgens) lowers SHBG. Testosterone Creams rise and fall quickly, cypionate keeps levels elevated 24/7.

How much estrogen is too much will depend on the individual, lower SHBG men have more Free E2 to worry about.

 

[Gman86]

So a few things. High SHBG will bind to E2 just like it does testosterone and DHT. It won’t bind to test and dht only, and let E2 float around unbound. So you have a more likely chance of your E2 not being high enough, rather than too high. 0.5mg of Arimidex twice a week is a very high dose. That is going to tank your E2, I can guarantee it. That dose has made my E2 go from 71, to single digits. So whatever you do, don’t take that high of a dose. I wouldn’t recommend an ai with your E2 and SHBG level, but if you do want to try it, start off with 0.125mg once per week, twice per week max. I promise you 0.5mg 2x/ week is going to be a horrible experience for you. Not exaggerating.

I’m trying to figure out why you felt so great at the beginning of using the cream, and then things got worse. The first thing that comes to everyone’s mind is obv that E2 accumulated and ruined everything. That might still be a possibility, but I’m not sure if that’s the culprit. Could it be that at the beginning you had some natural levels still going? Probably not though. You had just come off using testosterone cypionate. So that’s probably not it. I would maybe try increasing the dose to see if that helps. Other than that, all I can think of is maybe your E2 might need to come down a tiny tiny bit. Or maybe it needs to go up slightly. It’s hard to tell. Sometimes guys do well with their E2 around where their SHBG is. But all I know, is that if you do try to lower E2, start off with around 0.125mg/ week, to 0.125mg 2x/ week, or things are going to get even worse.

Now with thyroid, you’re absolutely on the right track. You need just straight T3 to lower RT3. Anything with T4 is going to usually make things worse. So I’m just wondering about that T3 tincture. You sure that’s something that’s been known to be effective? Why not just use the standard pharmaceutical or compounded T3 that we know works most of the time? Maybe you need to up your T3 dose. I’ve heard that you need to continue upping your dose pretty frequently, until you reach your optimal dose. If you stay at one dose for too long, the positive effects can disappear. You’re taking 12mcg of T3 right now. I’ve heard the optimal dosage of dessicated thyroid is usually 1-3 grains. Each grain contains 9mcg of T3. So usually the optimal dose of T3 people end up getting is about 9-27mcg. You’re on 12mcg, so maybe you just need to up your dose.

 

[Cataceous]

A free estradiol calculator puts your most recent number at about 0.9 pg/mL. Normal range is roughly 0.5 to 1.5 pg/mL. This would say if you want to experiment then you do have a little leeway before going too low. However, do heed Gman's advice to start lower with the AI.

For comparison, your first set of numbers above gives a calculated free estradiol of about 0.15 pg/mL, very low.

 

[Castaneda]

So a few things. High SHBG will bind to E2 just like it does testosterone and DHT. It won’t bind to test and dht only, and let E2 float around unbound. So you have a more likely chance of your E2 not being high enough, rather than too high. 0.5mg of Arimidex twice a week is a very high dose. That is going to tank your E2, I can guarantee it. That dose has made my E2 go from 71, to single digits. So whatever you do, don’t take that high of a dose. I wouldn’t recommend an ai with your E2 and SHBG level, but if you do want to try it, start off with 0.125mg once per week, twice per week max. I promise you 0.5mg 2x/ week is going to be a horrible experience for you. Not exaggerating.

You know, I slept on this one and woke up this morning feeling that I would just forego AI for now. I intuitively feel that my primary issue is high adiposity and suboptimal thyroid. I did an InBody 230 measurement in the doc's office before starting therapy. It showed lean body mass at 172.9 with a total weight of 215. That puts fat % just north of 19%. Since starting T therapy, my weight has gone up to 220 without making any changes whatsoever to diet or exercise. The first thing that came to my mind was increased water weight from estrogen, but I don't want to draw conclusions in a void like that anymore. This morning, I basically just sucked it up and said to myself, "OK, just drag yourself to lose that extra weight, widen the fasting window, and put carbs around workouts... and things will come in line".

I’m trying to figure out why you felt so great at the beginning of using the cream, and then things got worse. The first thing that comes to everyone’s mind is obv that E2 accumulated and ruined everything. That might still be a possibility, but I’m not sure if that’s the culprit. Could it be that at the beginning you had some natural levels still going? Probably not though. You had just come off using testosterone cypionate. So that’s probably not it. I would maybe try increasing the dose to see if that helps. Other than that, all I can think of is maybe your E2 might need to come down a tiny tiny bit. Or maybe it needs to go up slightly. It’s hard to tell. Sometimes guys do well with their E2 around where their SHBG is. But all I know, is that if you do try to lower E2, start off with around 0.125mg/ week, to 0.125mg 2x/ week, or things are going to get even worse.

I think your statement about SHBG and potentially low calc'd E2 are right on the money. I don't want to play Russian roulette with biology here. I don't have gynecomastia and emotions are stable. Further, my wife (who has a great body even after 3 kids) used to walk around naked at night and I'd be lucky to feel "in the mood". Now, she steps out of the shower, and I have to restrain myself to all but throw her on the bed, so let's put things into context. I'm probably just being greedy about how I "want to feel". I keep expecting I'm going to feel 20-something again, but I'm in my mid 40's.... so the gains here are probably not going to be fully realized until I drop this excess fat. That alone, will decrease aromatase. Previous labs had my sensitive E2 at 9, so I'm probably on the right track. I'm going to just ditch the AI for now and keep an eye on high-E2 warning signs. Like you said, there's a possibility I don't have enough E2 with my SHBG..... which brings me to the question.... any tips and tricks to lower SHBG? Just 10-15 points, and I'd probably feel like a million bucks.

Now with thyroid, you’re absolutely on the right track. You need just straight T3 to lower RT3. Anything with T4 is going to usually make things worse. So I’m just wondering about that T3 tincture. You sure that’s something that’s been known to be effective? Why not just use the standard pharmaceutical or compounded T3 that we know works most of the time? Maybe you need to up your T3 dose. I’ve heard that you need to continue upping your dose pretty frequently, until you reach your optimal dose. If you stay at one dose for too long, the positive effects can disappear. You’re taking 12mcg of T3 right now. I’ve heard the optimal dosage of dessicated thyroid is usually 1-3 grains. Each grain contains 9mcg of T3. So usually the optimal dose of T3 people end up getting is about 9-27mcg. You’re on 12mcg, so maybe you just need to up your dose.

So... thyroid. Yes. I'm using a liothyronine solution mixed with SFAs and ethanol. It's meant to be used as a topical at 8mcg / drop, but that kind of dose of straight T3 all at once would probably send me through the roof. So what I did was take 25 drops of it and mixed it in a 1 ounce glass bottle with a dropper, so that I could titrate to 1mcg per drop.

The thing is... I want to be careful with straight T3. Taking too much too long will completely tank endogenous production and TSH will plummet to next to nothing. This feels good as long as you're taking it, but if you stop for any reason, then there's a huge, potentially deadly crisis, because the body is no longer making sufficient T4. So that's why I've been going slowly with it. I called a local compounding pharmacy, and they said the lowest dose they could compound for me is 100mcg and asked why I would want anything lower. People are just shit-stupid, sometimes. Really.

The other thing about T3 is it has a short half-life when not paired with T4 (as in NDT). T4 slows uptake, whereas with T3, you have to really dose every 3-4 hours to get the same effect. There's no "take it in the morning and at night" as with NDT. That would cause a slump in the middle of the day.

 

[Gman86]

You know, I slept on this one and woke up this morning feeling that I would just forego AI for now. I intuitively feel that my primary issue is high adiposity and suboptimal thyroid. I did an InBody 230 measurement in the doc's office before starting therapy. It showed lean body mass at 172.9 with a total weight of 215. That puts fat % just north of 19%. Since starting T therapy, my weight has gone up to 220 without making any changes whatsoever to diet or exercise. The first thing that came to my mind was increased water weight from estrogen, but I don't want to draw conclusions in a void like that anymore. This morning, I basically just sucked it up and said to myself, "OK, just drag yourself to lose that extra weight, widen the fasting window, and put carbs around workouts... and things will come in line".



I think your statement about SHBG and potentially low calc'd E2 are right on the money. I don't want to play Russian roulette with biology here. I don't have gynecomastia and emotions are stable. Further, my wife (who has a great body even after 3 kids) used to walk around naked at night and I'd be lucky to feel "in the mood". Now, she steps out of the shower, and I have to restrain myself to all but throw her on the bed, so let's put things into context. I'm probably just being greedy about how I "want to feel". I keep expecting I'm going to feel 20-something again, but I'm in my mid 40's.... so the gains here are probably not going to be fully realized until I drop this excess fat. That alone, will decrease aromatase. Previous labs had my sensitive E2 at 9, so I'm probably on the right track. I'm going to just ditch the AI for now and keep an eye on high-E2 warning signs. Like you said, there's a possibility I don't have enough E2 with my SHBG..... which brings me to the question.... any tips and tricks to lower SHBG? Just 10-15 points, and I'd probably feel like a million bucks.



So... thyroid. Yes. I'm using a liothyronine solution mixed with SFAs and ethanol. It's meant to be used as a topical at 8mcg / drop, but that kind of dose of straight T3 all at once would probably send me through the roof. So what I did was take 25 drops of it and mixed it in a 1 ounce glass bottle with a dropper, so that I could titrate to 1mcg per drop.

The thing is... I want to be careful with straight T3. Taking too much too long will completely tank endogenous production and TSH will plummet to next to nothing. This feels good as long as you're taking it, but if you stop for any reason, then there's a huge, potentially deadly crisis, because the body is no longer making sufficient T4. So that's why I've been going slowly with it. I called a local compounding pharmacy, and they said the lowest dose they could compound for me is 100mcg and asked why I would want anything lower. People are just shit-stupid, sometimes. Really.

The other thing about T3 is it has a short half-life when not paired with T4 (as in NDT). T4 slows uptake, whereas with T3, you have to really dose every 3-4 hours to get the same effect. There's no "take it in the morning and at night" as with NDT. That would cause a slump in the middle of the day.

Sounds like you’re thinking very logically about everything, and are on the right track. I would definitely try to go without the ai. I’m doing this currently. My SHBG is 44, and my last E2 came back at 29. I think I feel better with higher E2. My libido was better when it was higher. I have a consultation next Friday to get put on thyroid medication. I really think my issues are with thyroid, and I’ve just been continuing to tweak my TRT protocol to fix issues that are really thyroid related.

So remind me, why are you on just T3 again instead of NDT? You have high reverse T3? And I’ve literally never heard of this form of T3 that you’re on. Have you heard of people having good results with it? Or read about other people’s experience with it?

 

[Castaneda]

So remind me, why are you on just T3 again instead of NDT? You have high reverse T3? And I’ve literally never heard of this form of T3 that you’re on. Have you heard of people having good results with it? Or read about other people’s experience with it?

Docs never understand my thyroid numbers. I'm a clinician myself (non-MD category), and I look at things from the "functional" perspective, so when they say things look fine or that NDT is required to bring things in line, I always question their reasoning.

Back in the early days, I tried .5 grain of NDT on and off, and every time it made me feel worse. It wasn't until I put 2 and 2 together and realized that I had more than enough T4 and that NDT (with its typical 4:1 ratio T4:T3) was overloading the balance.

What does the body do when there is too much T4? It converts it to RT3. And too much RT3 leads to clogged T3 receptors, so even if free T3 looks good, the body feels hypothyroid. The way my labs look are like this:

Free T4: 1.67 ng/dL (0.82-1.77)
Free T3: 3.8 pg/mL (2.0-4.4)
TSH: 3.1 uIU/mL (0.45-4.5)
RT3: 25.2 ng/dL (9.2-24.1)

See what I mean? A good clinician will ask why RT3 is high. Most docs don't even test for it. The most common reason -- high cortisol is slowing down the conversion of T4 > T3 and RT3 is pooling.

The only situation where you want to take straight T3 (without T4) is when this is happening. It's literally the only approach that will clear out that excess RT3. If free T4 is trending with a TSH above 1, then NDT is useful. Be careful, though, if free T4 looks good (as in my case).

It's not a long term strategy if the original cortisol problem isn't fixed. In my case, cortisol was tending to go high because of estrogen. Higher estrogen results in higher reactivity to antigens (think allergies). Allergic reactions tend to raise cortisol. On my labs, eosinophils are always high.... They have finally been coming down because T is going up. As a matter of fact, this allergy season (after starting T therapy), I had no allergic symptoms. None. There is a reason women suffer more from asthma than men, especially during their cycle.

Estrogen effects in allergy and asthma

I have some good news to report, actually --- I think I've found a solution for my high SHBG and lack of response from testosterone. I had a flash of insight last night -- and it occurred to me that by raising testosterone, it's triggered a biofeedback look in the steroid hormone chain to slow down Pregnenolone / DHEA production --- they simply aren't needed when exogenous supply has increased. Then I remembered that my Progesterone has been low on previous labs. Just as an experiment last night, I rubbed a topical solution of Progesterone / DHEA onto my forearms (5mg / 5mg) and literally within a couple of hours, I felt completely different. The weak erections immediately disappeared.

So I need to dig a little more in this area. Progesterone and DHEA together synergistically bring down cortisol -- and that's ultimately what's interfering with both thyroid and testosterone.

It makes you think ... how many men out there have optimal hormone levels but aren't getting the benefits because cortisol is too high? I think it should be mandatory for guys to do a 4-point salivary test before fooling around with other options, especially those that "overtrain". Everyone knows that too much training is catabolic, primarily through excess cortisol.

Bit by bit, this will all become clearer.

If you are curious about the T3 drops I have been using, a lot of the "peptide shops" sell it. You can also do some hunting around the Ray Peat forum, as that crowd seems to be very pro-thyroid (a more is better mentality). But again, don't touch straight T3 if your T4 is going low. You can benefit from NDT instead.

 

[fifty]

You talked about topical dhea/preg in your first post back in November. Round and round we go?