High estrogens / SHBG

[Castaneda]

I wanted to wait a few days before posting an update, to assess things more thoughtfully.

I had a consult with Defy last week. I didn't have an opportunity to speak to a doctor, just a knowledgeable PA, but he seemed to have a few more "angles" on the matter than my current practitioner. He also concurred with me that the current provider is way off the mark, in multiple ways.

The summary is:

1. Some autoimmune or similar condition is kicking in and causing RT3 to spike. The labs show inconsistent numbers. T4 is coming down as a result of the Cytomel I've been taking, but RT3 is rising. My feeling is this is viral, because the high RT3 is often accompanied by cold sores. He thought a course of Acyclovir would be useful, but that's just a band-aid.
   
   I'm going to maximize sun exposure as the temps are now rising. That seems to correct RT3 problems, at least in the summer. In the meantime, the plan is to gradually increase Cytomel. I've been taking 5mcg 5x a day ... a total of 25mcg / day. He said I could go as high as 50 if I had to until RT3 was in the single digits. This makes sense.
   
   
2. Testosterone, estrogen, and DHT have all shot up since the last labs. This is because the last lab was taken before I was advised to apply T-cream trans-scrotally. DHT is high enough to cause libido issues (so the PA believes). He says it shot up because of putting so much T-cream on the scrotum. As a matter of fact, SHBG going higher is likely a sign that the body is trying to deal with excess steroid hormones, in general.
   
   The advice here was to stop applying 400mg / day to the scrotum (which was really ill-conceived to begin with) and take the dose down to 100mg, 2x a day, applied elsewhere.

So I have halved my dose and was putting it on the inner thigh and stopped Prog / DHEA completely. 2 days later I slipped into one of the worst depressions of my life. Soul-crushing anhedonia. Absolutely no motivation to do anything, suicidal ideations, the works.

In desperation, last night, I took 5mg of Prog and DHEA again, and literally within 20 minutes, everything came back online. Libido, desire, motivation, well-being. This is not placebo, trust me. Given my symptoms, I can't figure out whether I have low E from high SHBG or high E from excessive conversion of T (from over-dosing). I'm leaning toward the latter because Progesterone blocks estrogen's effects at low levels (3-5 mg). As a matter of fact, I'm very inclined to start recommending it as a natural "estrogen control" mechanism.. as soon as I can confirm that's actually what it's doing.

Long-term, the advice was to get off the cream altogether and start using sub-Q T-cypionate. But we're going to test levels first in 4 weeks to see where halving the dose has landed me. He did recommend taking 25mg of DHEA before bed along with the 5mg of Progesterone, but the thought of that unnerves me. DHEA at levels over 5mg pushes my estrogen up.

The problem at hand is figuring out what Progesterone (combined with DHEA) is doing. It has such a pronounced effect on libido and going without it causes huge problems .... I'm going to need to vet it out thoroughly. I will be ordering some straight Prog and trying that without DHEA. Then DHEA alone, both in the same amounts (5mg). Intuition says it's the combination here, but let's see where things go.

I expressed a concern that sub-Q T injections would aromatize more heavily due to higher enzymatic activity in adipocytes, but the PA didn't seem to agree that would happen. I still have enough body fat that it's a concern, nonetheless.

One thing is for certain -- something is having its way with my immune system, and it's dragging my metabolism into the dirt. It could be I need to be much more aggressive with the Cytomel in these "troughs", but I don't want to flip over to hyper-thyroid.

 

[Castaneda]

For anyone that's interested in following this research with me, here is the article I came across before deciding to start Prog + DHEA:

6-Ketoprogesterone and its biological actions

The results are summarized in Table 6.

The extracts of the samples, in which progesterone and dehydroepiandrosterone were used as substrate resulted in the strongest hypertrophy of the preputial gland and had the strongest myotrophic action of all. Both of the actions of the products which come from the incubation of the villus with 17(a)-hydroxyprogesterone were much weaker."

If you go far enough down this rabbit hole, you'll find that this combo has multiple biological effects, including anti-cortisol, anti-viral, anti-mutagenic, anti-inflammatory, anti-endotoxin, antimicrobial, anti-cancer, and more. I have a feeling it's a piece of the puzzle that is missing in a lot of men that suppress their endogenous steroid hormone production with T therapy.

The other clue for me has been my consistently high Pregnenolone levels (when tested). While I do consume a diet higher in fat / cholesterol, Pregnenolone levels should not be high if it is converting properly to Progesterone and DHEA. I remember always having bad effects when taking Pregnenolone. It (subjectively) feels like it is causing a rise in cortisol.

 

[fifty]

Glad you are feeling better. Can you order and couple E2 sensitive tests then get the blood draws when you’re feeling good and then when you’re feeling bad? Seems like a pain but might be good info?

 

[Cataceous]

...
I expressed a concern that sub-Q T injections would aromatize more heavily due to higher enzymatic activity in adipocytes, but the PA didn't seem to agree that would happen. I still have enough body fat that it's a concern, nonetheless.
...

Transdermal testosterone is more of a concern for aromatization, as the pure testosterone may encounter aromatase during absorption. Injected testosterone esters, however, do not aromatize. When they finally enter the bloodstream they encounter esterase, which cleaves the ester and frees the testosterone. Only then may aromatization to estradiol occur.

 

[Castaneda]

Transdermal testosterone is more of a concern for aromatization, as the pure testosterone may encounter aromatase during absorption. Injected testosterone esters, however, do not aromatize. When they finally enter the bloodstream they encounter esterase, which cleaves the ester and frees the testosterone. Only then may aromatization to estradiol occur.

Which begs the question: why isn't sub-Q administration advocated more if it is just as effective as IM? Or is there an issue with absorption?

 

[Castaneda]

Glad you are feeling better. Can you order and couple E2 sensitive tests then get the blood draws when you’re feeling good and then when you’re feeling bad? Seems like a pain but might be good info?

I wish I could say it's E2, but that SHBG is a huge problem. It was the main reason I was started out on such a high dose (supposedly to overcome binding and get better free T). The last lab shows a high free T, but SHBG shot up again (along with RT3).

Doing two ultra-sensitive E2 tests would be over $200. Rather expensive for just a hunch, but I will keep it in the back of my mind if I can't get any traction. I am feeling quite a bit better today. I think SHBG is likely starting to come down again now that T and E2 levels aren't exploding.

 

[fifty]

E2 sensitive is $43 on discounted labs

 

[Cataceous]

Which begs the question: why isn't sub-Q administration advocated more if it is just as effective as IM? Or is there an issue with absorption?

No problems with absorption. There's a good clinical trial showing it's the same. The half-life is longer with subQ. It's not advocated more due to inertia and conservatism: doctors have been hesitant to do other than what the manufacturers recommended.

 

[Castaneda]

I feel obligated to post an update here, even though it's not a positive one.

Over the past three weeks, I've followed Defy Medical's advice and cut my T Cypionate dose in half and switched out the Liothyronine drops I had been using for Sustained Release capsules from "Empower" Pharmacy. Everything has fallen apart. Within a week of getting on the Liothyronine capsules from Empower, my temps took a sharp drop from 98.2 to 97.9. As soon as I phased the drops out completely and went full-time on the capsules, the temps continued to decline. Now I am at a new low of 97.5 with even less energy and stamina than before. I can honestly say I have never felt this terrible in my entire life.

So I'm coming to a few conclusions at this point:

1. It's possible that Empower is not a 100% legitimate pharmacy. I don't have time or resources at the moment to test their product, but I am now on 15mcg of SR Liothryonine, 2x a day (that's a total of 30mcg / day), and I feel absolutely nothing. I've gone full-blown hypothyroid, with low temps and zero energy. I have no issues digesting other SR type products, so it's not the substrate they are using.
   
   I would imagine other people would complain if they were getting sugar pills, but then it's also possible that a lot of people are suffering out there without knowing for sure what it is, believing that the medicine is real. All I can say is I will have to soon go back on the drops, since they were at least keep my energy and temps stably high.
   
   After this experience, it is not likely I will use Empower again. I looked them up on the BBB site, and they have an A+ rating with zero complaints. If anyone on this forum would like to collect funds together and test medication content with a 3rd party, PM me. It could be no one has spoken out yet.
   
   
2. Cutting the T dose in half has taken libido from low to non-existent. Without wanting to pay $700 again for tests (which is what Defy charged me), I will go out on a limb and say that I'm likely not getting enough T to overcome SHBG and with the now elevated RT3 from taking T3 of questionable strength / quality, the effect is even more pronounced (i.e. feelings of low estrogen and anhedonia).

Doing my best to keep a positive outlook, but every area of life has been affected. At this point, I wish I had never touched TRT and could go back to my low-energy life with good mood and decent libido. Defy has no follow-up. They basically rip your wallet for a load of tests, give the Empower Pharmacy meds and send you on your way. There is no one to turn to to discuss side effects or problems. I suppose that's par for the course with tele-medicine these days. Answering questions would be time-consuming.

That's it for now. Not sure what to do at this point. Maintaining my client load and getting things done has become an enormous task. I spent 3 hours yesterday (during the middle of the day) sleeping. My energy has gone from manageable to non-existent, for the most part. Just a few months ago, before I started this ridiculous experiment, I was running laps around my neighborhood, unable to tire myself out. And that was without T, without sugar pills, and without people pretending to know biology, guessing what the problem is.

Once you get on this train, there is no reasonable exit strategy. You are chained to it, like it or not.

 

[fifty]

Sorry to hear that. So many substances tried it’s hard to tell what’s doing what. I understand to some minor degree as I can’t even figure out test hcg dhea and anastrozole. I didn’t know what anxiety was until I started all this stuff.

You are yet another member of the T 600 plus club pre trt that has had struggles. @JayLay777

 

[fifty]

It might help to post what you’re currently taking. It’s hard to determine from your posts. Last I could determine you were still on topical T.

You can get generic liothyronine from walgreens pharmacy for $40 90tabs 25mcg. Hell brand name cytomel is in a similar price range as your compounded stuff. Cytomel is $80 for 30tabs 25mcg or $125 for 30tabs 50mcg. Cytomel is scored for easy splitting in half.

If it were me on liothyronine I’d have them call in a prescription for cytomel so I could stop worrying about that. Not the cheapest solution but I’ll gladly pay for peace of mind any day if I’m feeling way off.

 

[MarcoFL]

I feel obligated to post an update here, even though it's not a positive one.

Over the past three weeks, I've followed Defy Medical's advice and cut my T Cypionate dose in half and switched out the Liothyronine drops I had been using for Sustained Release capsules from "Empower" Pharmacy. Everything has fallen apart. Within a week of getting on the Liothyronine capsules from Empower, my temps took a sharp drop from 98.2 to 97.9. As soon as I phased the drops out completely and went full-time on the capsules, the temps continued to decline. Now I am at a new low of 97.5 with even less energy and stamina than before. I can honestly say I have never felt this terrible in my entire life.

So I'm coming to a few conclusions at this point:

1. It's possible that Empower is not a 100% legitimate pharmacy. I don't have time or resources at the moment to test their product, but I am now on 15mcg of SR Liothryonine, 2x a day (that's a total of 30mcg / day), and I feel absolutely nothing. I've gone full-blown hypothyroid, with low temps and zero energy. I have no issues digesting other SR type products, so it's not the substrate they are using.
   
   I would imagine other people would complain if they were getting sugar pills, but then it's also possible that a lot of people are suffering out there without knowing for sure what it is, believing that the medicine is real. All I can say is I will have to soon go back on the drops, since they were at least keep my energy and temps stably high.
   
   After this experience, it is not likely I will use Empower again. I looked them up on the BBB site, and they have an A+ rating with zero complaints. If anyone on this forum would like to collect funds together and test medication content with a 3rd party, PM me. It could be no one has spoken out yet.
   
   
2. Cutting the T dose in half has taken libido from low to non-existent. Without wanting to pay $700 again for tests (which is what Defy charged me), I will go out on a limb and say that I'm likely not getting enough T to overcome SHBG and with the now elevated RT3 from taking T3 of questionable strength / quality, the effect is even more pronounced (i.e. feelings of low estrogen and anhedonia).

Doing my best to keep a positive outlook, but every area of life has been affected. At this point, I wish I had never touched TRT and could go back to my low-energy life with good mood and decent libido. Defy has no follow-up. They basically rip your wallet for a load of tests, give the Empower Pharmacy meds and send you on your way. There is no one to turn to to discuss side effects or problems. I suppose that's par for the course with tele-medicine these days. Answering questions would be time-consuming.

That's it for now. Not sure what to do at this point. Maintaining my client load and getting things done has become an enormous task. I spent 3 hours yesterday (during the middle of the day) sleeping. My energy has gone from manageable to non-existent, for the most part. Just a few months ago, before I started this ridiculous experiment, I was running laps around my neighborhood, unable to tire myself out. And that was without T, without sugar pills, and without people pretending to know biology, guessing what the problem is.

Once you get on this train, there is no reasonable exit strategy. You are chained to it, like it or not.

I have tried SR T3 and regular T3 and found the SR was inconsistent.

 

[Gman86]

I wouldn’t stress too much. I agree with fifty, I would just get on some cytomel. I personally wouldn’t touch the generic stuff. According to the FDA, generics are allowed to have a broad variance in efficacy, compared to brand names. Here’s the exact excerpt.

The FDA’s rules effectively acknowledge that. The agency’s definition of bioequivalence is surprisingly broad: A generic’s maximum concentration of active ingredient in the blood must not fall more than 20% below or 25% above that of the brand name. This means a potential range of 45%, by that measure, among generics labeled as being the same

As far as Empower not being legit, or improperly dosing their sustained release T3, I think we can easily disregard that type of thinking. They’re one of the top compounding pharmacies for a reason. I think they know how to make sustained release T3. No offense to you or anything. I can understand why you could come to the conclusion that they might not be legit, or might not know what they’re doing. Clearly you’re becoming more symptomatic and your temps are dropping. But I think it would be more likely that the dosing for sustained release T3 might be different than quick release T3. You may just need way more SR T3. But if I was you, I would personally just hop on some quick acting T3. Either from Empower, or get on Cytomel. Whatever you do, stay away from the generics. They obv work for some people, but I wouldn’t subject myself to a medication that may not be consistent, when you can take a consistent brand name version for around the same price. Even if it was double the price, I’d still take brand name. When it comes to your health, why mess around.

And if I were you I would probably increase your test cyp dose. How much? That you would know better than us.

Oh, the last thing, only T4 containing medications can increase RT3. I think you mentioned something about your RT3 going up on the SR T3. That’s impossible, from my understanding. If anything, just taking straight T3 usually always lowers RT3.

 

[Castaneda]

No time for a prolonged update now, but the problem was SR Liothyronine, as I had suspected. I skipped the second dose right after the last post and went straight for 5mcg of the Liothyronine drops I had been using before. Within just 15 minutes, all symptoms disappeared and I was back to baseline. Within 30 minutes, temps were at 98.2 again. Next morning, I was completely back to normal.

As far as Empower not being legit, or improperly dosing their sustained release T3, I think we can easily disregard that type of thinking. They’re one of the top compounding pharmacies for a reason. I think they know how to make sustained release T3. No offense to you or anything. I can understand why you could come to the conclusion that they might not be legit, or might not know what they’re doing. Clearly you’re becoming more symptomatic and your temps are dropping. But I think it would be more likely that the dosing for sustained release T3 might be different than quick release T3. You may just need way more SR T3. But if I was you, I would personally just hop on some quick acting T3. Either from Empower, or get on Cytomel. Whatever you do, stay away from the generics. They obv work for some people, but I wouldn’t subject myself to a medication that may not be consistent, when you can take a consistent brand name version for around the same price. Even if it was double the price, I’d still take brand name. When it comes to your health, why mess around.

I will say this --- between 5mcg, 10mcg, and 15mcg Liothyronine SR from Empower, none of them produced any noticeable result. If I take, for example, just 1-2 drops of my Liothyronine solution sublingually, it is tangible. Heart-rate goes up slightly and temps respond. Nonetheless, 5mcg is the minimum dose for me to feel "normal". So if, for example, the 15mcg T3 SR were bound to a medium that was releasing liothyronine over, say, a 12 hour period, then we would see only ~1-2mg per hour over that period. To get 5mcg levels sustained, I'd have to take 5x that dose in SR format. That would be 75mcg SR, and the highest dose most pharmacies consider for SR is 35mcg. Then there is the question of the potential for severe spikes as a result of inconsistent release. At that level, it would be risky business. Hell, it's risky business taking more than 5mcg instant release at a time, IMHO. Double that risk for sublingual route.

I have samples of all three of the Empower SR capsules (5,10,15) and will be sending them off for analysis later this week (simply to satisfy my curiosity about them). As for a compounding pharmacy "knowing how to make SR T3", there is no way to know without testing their output. In my own experience (with the labs where we run experiments), the only consistent results were seen with liposomes and drug-polymer conjugates (e.g. hydrogels). The powdered excipients, as @Mark Saur mentioned, are not consistent. This is a question of how they are being broken down along the digestive tract. My GI system is relatively clean, according to recent testing, but there could conceivably be some fermentation of foods or other issues that prevent proper degradation. That would be the only explanation -- apart from a lack of medication bound to the excipient.

I have no desire at this point to go after prescription Cytomel, brand name or generic. The drops I am using are working perfectly fine. The big challenge for me now is titrating up to the desired 50mcg total / day, since over 5mcg instant release I get palpitations. I have considered mixing it with short-chain fatty acids and ethanol and using topically. I have done that with other substances in the past and get fairly good results.

Also, I failed to mention that I also ordered Cialis SR through Empower and got no result from that as well, so chances are high that I'm not breaking down the SR excipient properly. I can't imagine other people aren't encountering similar issues.

It might help to post what you’re currently taking. It’s hard to determine from your posts. Last I could determine you were still on topical T.

Apologies this was not clear. This is the line-up right at this moment:

• Testosterone Cypionate liposomal cream transcrotally (100mg BID)
• Liothyronine USP, 5mcg, 5x / day sublingually
• Progesterone / DHEA in tocopherols, 5mg/5mg, QD before bed

Nothing else.

Frankly, to me, it seems like you are fixated on some arbitrary set of numbers, and thinking yourself in circles. The obsession of how you are feeling minute to minute and moment to moment indicates the problem isn’t between your legs, but between your ears. I’d spend some time with a mental health professional to get to the underlying cause of your dissatisfaction with your life.

But I’m just a recovering addict, so what do I know? *shrug*

Odd, how did you come to the conclusion I am measuring progress in minutes or hours? My methodology looks at subjective results once weekly with labs monthly or bimonthly. That's it. My updates here on the forum are few and far between. I am a mental health professional (with a focus in neurobiology). The majority of people in that particular field have their head stuffed halfway up their rear ends, prescribing Xanax and SSRIs to unsuspecting people with anxiety / depression. If you want to talk about the biology of anhedonia, please, that's in my wheelhouse. I'm all ears. I presume you will also tell my patients with Parkinson's and Alzheimer's that their neurodegeneration is also in their heads, yes?

Neuroendocrine dysregulation is neither exclusively in the head nor between the legs. It's both. Treating one or the other in isolation only leads to trouble. Sometimes, we don't lay all of our cards on the table, so as not to confuse matters. There are holes in my knowledge of endocrinology. I am here to connect dots.

Oh, the last thing, only T4 containing medications can increase RT3. I think you mentioned something about your RT3 going up on the SR T3. That’s impossible, from my understanding. If anything, just taking straight T3 usually always lowers RT3.

Yes, what I was referring to is the lack of T3 present to counteract already high RT3. I don't want to drag this thread into the deep research I've been doing with immunological pathways and autoimmunity. I'm quite sure I understand what's pushing my naturally normal-high T4 to RT3, but that's a separate affair. My RT3 was going up on SR T3 because of the absence of a sufficient concentration of T3 over time. That being said, 30mcg of my solution spread over ~16 hours, while stabilizing temperatures and getting heart-rate up, still does not bring down RT3 to the single digits, so I have some thinking to do regarding the proper approach. Topical route might be the answer, somewhat more predictable than GI tract. Increasing number of sublingual doses would also work to keep levels consistent, but a logistical nightmare.

I'm going to probably need to look into liposomal compounding. If there are enough people struggling with SR, then there may be a justification to secure funding for a more formal offering. As for what to do about my high SHBG, I haven't heard any plausible theories on that one yet. Why is the liver increasing SHBG output? I still say it does that in a Th2-skewed immune profile where histamine, mast cells, and estrogen are conspiring with each other.

Role of female sex hormones, estradiol and progesterone, in mast cell behavior

My pattern --- estradiol rises, mast cell destabilization, astroglial / microglial activation, induction of Herpes and EBV viral lytic cycle. HSV-2 fever blisters appear in various areas during this cycle combined with hypersensitivity to foods, allergens, etc. How do you capture that on a lab when SHBG is surging up to bind a great deal of it (estrogens)? The lab will show "normal-high" estradiol. Men need to start thinking about these things, especially if they have a history of asthma. None of the hormone docs get it. Do you think this profile could also cause oxidative stress to dopaminergic neurons and lower hedonistic tone / i.e. wreck the "reward pathway"? Yes. And consider this:

Effects of thyroid hormone on HSV-1 gene regulation: implications in the control of viral latency and reactivation

Consistent immune activation leads to high RT3 which leads to less inhibition of viruses which leads to.... you guessed it. This isn't overthinking. This is the key to understanding the neuroendocrine disruptions in a large number of men that aren't responding to T therapy. Problem is, none of it is clear when your RT3 is high. LOL.

 

[Gman86]

No time for a prolonged update now, but the problem was SR Liothyronine, as I had suspected. I skipped the second dose right after the last post and went straight for 5mcg of the Liothyronine drops I had been using before. Within just 15 minutes, all symptoms disappeared and I was back to baseline. Within 30 minutes, temps were at 98.2 again. Next morning, I was completely back to normal.



I will say this --- between 5mcg, 10mcg, and 15mcg Liothyronine SR from Empower, none of them produced any noticeable result. If I take, for example, just 1-2 drops of my Liothyronine solution sublingually, it is tangible. Heart-rate goes up slightly and temps respond. Nonetheless, 5mcg is the minimum dose for me to feel "normal". So if, for example, the 15mcg T3 SR were bound to a medium that was releasing liothyronine over, say, a 12 hour period, then we would see only ~1-2mg per hour over that period. To get 5mcg levels sustained, I'd have to take 5x that dose in SR format. That would be 75mcg SR, and the highest dose most pharmacies consider for SR is 35mcg. Then there is the question of the potential for severe spikes as a result of inconsistent release. At that level, it would be risky business. Hell, it's risky business taking more than 5mcg instant release at a time, IMHO. Double that risk for sublingual route.

I have samples of all three of the Empower SR capsules (5,10,15) and will be sending them off for analysis later this week (simply to satisfy my curiosity about them). As for a compounding pharmacy "knowing how to make SR T3", there is no way to know without testing their output. In my own experience (with the labs where we run experiments), the only consistent results were seen with liposomes and drug-polymer conjugates (e.g. hydrogels). The powdered excipients, as @Mark Saur mentioned, are not consistent. This is a question of how they are being broken down along the digestive tract. My GI system is relatively clean, according to recent testing, but there could conceivably be some fermentation of foods or other issues that prevent proper degradation. That would be the only explanation -- apart from a lack of medication bound to the excipient.

I have no desire at this point to go after prescription Cytomel, brand name or generic. The drops I am using are working perfectly fine. The big challenge for me now is titrating up to the desired 50mcg total / day, since over 5mcg instant release I get palpitations. I have considered mixing it with short-chain fatty acids and ethanol and using topically. I have done that with other substances in the past and get fairly good results.

Also, I failed to mention that I also ordered Cialis SR through Empower and got no result from that as well, so chances are high that I'm not breaking down the SR excipient properly. I can't imagine other people aren't encountering similar issues.



Apologies this was not clear. This is the line-up right at this moment:

• Testosterone Cypionate liposomal cream transcrotally (100mg BID)
• Liothyronine USP, 5mcg, 5x / day sublingually
• Progesterone / DHEA in tocopherols, 5mg/5mg, QD before bed

Nothing else.



Odd, how did you come to the conclusion I am measuring progress in minutes or hours? My methodology looks at subjective results once weekly with labs monthly or bimonthly. That's it. My updates here on the forum are few and far between. I am a mental health professional (with a focus in neurobiology). The majority of people in that particular field have their head stuffed halfway up their rear ends, prescribing Xanax and SSRIs to unsuspecting people with anxiety / depression. If you want to talk about the biology of anhedonia, please, that's in my wheelhouse. I'm all ears. I presume you will also tell my patients with Parkinson's and Alzheimer's that their neurodegeneration is also in their heads, yes?

Neuroendocrine dysregulation is neither exclusively in the head nor between the legs. It's both. Treating one or the other in isolation only leads to trouble. Sometimes, we don't lay all of our cards on the table, so as not to confuse matters. There are holes in my knowledge of endocrinology. I am here to connect dots.



Yes, what I was referring to is the lack of T3 present to counteract already high RT3. I don't want to drag this thread into the deep research I've been doing with immunological pathways and autoimmunity. I'm quite sure I understand what's pushing my naturally normal-high T4 to RT3, but that's a separate affair. My RT3 was going up on SR T3 because of the absence of a sufficient concentration of T3 over time. That being said, 30mcg of my solution spread over ~16 hours, while stabilizing temperatures and getting heart-rate up, still does not bring down RT3 to the single digits, so I have some thinking to do regarding the proper approach. Topical route might be the answer, somewhat more predictable than GI tract. Increasing number of sublingual doses would also work to keep levels consistent, but a logistical nightmare.

I'm going to probably need to look into liposomal compounding. If there are enough people struggling with SR, then there may be a justification to secure funding for a more formal offering. As for what to do about my high SHBG, I haven't heard any plausible theories on that one yet. Why is the liver increasing SHBG output? I still say it does that in a Th2-skewed immune profile where histamine, mast cells, and estrogen are conspiring with each other.

Role of female sex hormones, estradiol and progesterone, in mast cell behavior

My pattern --- estradiol rises, mast cell destabilization, astroglial / microglial activation, induction of Herpes and EBV viral lytic cycle. HSV-2 fever blisters appear in various areas during this cycle combined with hypersensitivity to foods, allergens, etc. How do you capture that on a lab when SHBG is surging up to bind a great deal of it (estrogens)? The lab will show "normal-high" estradiol. Men need to start thinking about these things, especially if they have a history of asthma. None of the hormone docs get it. Do you think this profile could also cause oxidative stress to dopaminergic neurons and lower hedonistic tone / i.e. wreck the "reward pathway"? Yes. And consider this:

Effects of thyroid hormone on HSV-1 gene regulation: implications in the control of viral latency and reactivation

Consistent immune activation leads to high RT3 which leads to less inhibition of viruses which leads to.... you guessed it. This isn't overthinking. This is the key to understanding the neuroendocrine disruptions in a large number of men that aren't responding to T therapy. Problem is, none of it is clear when your RT3 is high. LOL.

I couldn’t agree more with things being multifactorial. People love to take sides, or think the cause/ cure for something is one thing. But that’s not how the body works. It usually is always a combination of things. I laugh when I see people argue on here, and try to get the other person to see why they’re correct. It makes me laugh because it’s usually a case of both of them are correct, just arguing different points. Are things all in our heads? Nope. Are they all physiological? Nope. Are they a mix of both 99.9% of the time, yup.

And hopefully you can titrate up your T3 dose without getting any wanted side effects. The STTM FB group recommends titrating up 5mcg every 5-7 days. They say to avoid unwanted side effects, when taking thyroid medication, cortisol and iron levels have to be optimal.

 

[Tman]

I wanted to wait a few days before posting an update, to assess things more thoughtfully.

I had a consult with Defy last week. I didn't have an opportunity to speak to a doctor, just a knowledgeable PA, but he seemed to have a few more "angles" on the matter than my current practitioner. He also concurred with me that the current provider is way off the mark, in multiple ways.

The summary is:

1. Some autoimmune or similar condition is kicking in and causing RT3 to spike. The labs show inconsistent numbers. T4 is coming down as a result of the Cytomel I've been taking, but RT3 is rising. My feeling is this is viral, because the high RT3 is often accompanied by cold sores. He thought a course of Acyclovir would be useful, but that's just a band-aid.
   
   I'm going to maximize sun exposure as the temps are now rising. That seems to correct RT3 problems, at least in the summer. In the meantime, the plan is to gradually increase Cytomel. I've been taking 5mcg 5x a day ... a total of 25mcg / day. He said I could go as high as 50 if I had to until RT3 was in the single digits. This makes sense.
   
   
2. Testosterone, estrogen, and DHT have all shot up since the last labs. This is because the last lab was taken before I was advised to apply T-cream trans-scrotally. DHT is high enough to cause libido issues (so the PA believes). He says it shot up because of putting so much T-cream on the scrotum. As a matter of fact, SHBG going higher is likely a sign that the body is trying to deal with excess steroid hormones, in general.
   
   The advice here was to stop applying 400mg / day to the scrotum (which was really ill-conceived to begin with) and take the dose down to 100mg, 2x a day, applied elsewhere.

So I have halved my dose and was putting it on the inner thigh and stopped Prog / DHEA completely. 2 days later I slipped into one of the worst depressions of my life. Soul-crushing anhedonia. Absolutely no motivation to do anything, suicidal ideations, the works.

In desperation, last night, I took 5mg of Prog and DHEA again, and literally within 20 minutes, everything came back online. Libido, desire, motivation, well-being. This is not placebo, trust me. Given my symptoms, I can't figure out whether I have low E from high SHBG or high E from excessive conversion of T (from over-dosing). I'm leaning toward the latter because Progesterone blocks estrogen's effects at low levels (3-5 mg). As a matter of fact, I'm very inclined to start recommending it as a natural "estrogen control" mechanism.. as soon as I can confirm that's actually what it's doing.

Long-term, the advice was to get off the cream altogether and start using sub-Q T-cypionate. But we're going to test levels first in 4 weeks to see where halving the dose has landed me. He did recommend taking 25mg of DHEA before bed along with the 5mg of Progesterone, but the thought of that unnerves me. DHEA at levels over 5mg pushes my estrogen up.

The problem at hand is figuring out what Progesterone (combined with DHEA) is doing. It has such a pronounced effect on libido and going without it causes huge problems .... I'm going to need to vet it out thoroughly. I will be ordering some straight Prog and trying that without DHEA. Then DHEA alone, both in the same amounts (5mg). Intuition says it's the combination here, but let's see where things go.

I expressed a concern that sub-Q T injections would aromatize more heavily due to higher enzymatic activity in adipocytes, but the PA didn't seem to agree that would happen. I still have enough body fat that it's a concern, nonetheless.

One thing is for certain -- something is having its way with my immune system, and it's dragging my metabolism into the dirt. It could be I need to be much more aggressive with the Cytomel in these "troughs", but I don't want to flip over to hyper-thyroid.

I'm reading through your post saying slow down...stop making so many changes so quickly... you are chasing your tail. Make one change at a time and give your body time to adjust.