I Feel Like I'm Dying After 12 Months of TRT. Something Else Isn't Right

Pharma TRT
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I sincerely don’t think our discussion are really useful for the guy that has started the conversation, but just to clarify: if you are referring about brain serotonin levels, the relation is not so clear, and a lot of the time (depending on the methods used in the study) it can be mediated by conversion to estradiol. The only thing of we can be sure, is that estrogen increase serotonin levels and serotonin 5-ht2a. Studies of pure androgens on brain chemistry are less clear, mixed and sometimes contradictory, they suggested a more responsive serotonin system by upregulating some type of receptors (like 5-ht1a) or the response to releasing agents, increasing synthesis and degradation. But the net result is another story, given the effect on other neurotransmitters with opposing effects. Here the effects of testosterone (without manipulation on the natural aromatization) is well predictable, and translate in an opposing effect between testosterone and serotonin. You can read some references here, but there are a lot more

Moreover, it doesn’t require to cite these studies to know the opposing effects of testosterone and serotonin: I fly over the pro-anxiety and pro-depressive effect of having high serotonin levels via SERT dysfunction, given that it is a too big argument to treat in a discussion like this, but all the other effects of high serotonin, like low sexual drive and low impulsivity, are clearly the opposite of those of testosterone.

Regarding aerobic training, the argument seems a nonsense for me: I imagine that he even drinks water daily, and the fact the this has not helped with his condition, does not mean that he should stop drinking water. A little aerobic is a must for all people, especially for depressed ones or for people that like him need to have healthy balanced routines.

Same for coffee: what are you talking about with this attempt at irony? He has clearly stated having a huge problem with insomnia, that in itself brings a lot of trouble: how can you recommend drinking more coffee, only for an alleged lack of catecholamines which, if so, should be treated differently?

I too often find myself at odds with the dominant thinking, and I appreciate this side of your arguments, but try to be cautious in suggestions

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Because he felt his worst at the highest free T. That’s why. His E2 is not coming up in ratio when he raises the dose.

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Serotonin and dopamine live on opposite sides of a level. If one goes up, the other goes down, that’s how they exist. I will read the studies as I get some time, I’m always interested in them. As someone with dopamine issues, I can tell you that the idea that caffeine = insomnia is a ridiculous statement when made in blanket fashion. I absolutely does not operate that way in everyone, and especially in people why dopamine problems. His general lack of estrogen is an obvious direct cause and effect relationship with serotonin and catecholamine issues, and estrogen is dependent on have the free testosterone available to make it, so they really can’t be considered independently. And while aerobic health is generally good just like a consumption of water, it does not have any great impact on catecholmines when done in greater quantity or if the person is in reasonable cardiovascular shape. Heavy lifting has an impact like stimulants, it directly stimulates your catecholamine production and availability. I can run all day and not get that, or I can do a couple of sets of squats or deadlifts and be a new man.

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Tell that to my extremely adhd wife. She can take caffeine or Sudafed for that matter and go right to sleep, so weird. I’d be up all night

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Exactly. It’s a ridiculous generalization people make, because that’s how it affects them.

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OP: i looked over some of your bloods and we shares similar issues. I too haven’t found much libido or anthing else from TRT.

I’ve been there, done that, in terms of protocols. SO, right now, i’m trying a larger than normal “cycle” if you will, just to see if i can locate libido or a positive benefit from TRT. I"m on a 250mg/week E3.5D protocol right now. (125mg e3.5d)

I’ll post back and let you know results. Maybe you just need a much larger dose. I know you stated you felt off with higher FT, but maybe you just need to break through where you were at.

Just a thought.

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Yes I think there is a neurotransmitter imbalance which has lead to an over-production of acetylcholine (triggering hyperhidrosis) and a deficiency in something else. I do not know what is upregulatory/downregulatory to acetylcholine.

All I know is that the past 2-3 weeks I’ve been feeling at my worst, I started drinking this Branched Chain Amino Acid and Recovery mix, which are effectively just a boatload of amino acids.

This has lead to extreme feelings of stress at night and staying up until 3-4 am.

I stopped drinking it and going to the gym the past few days and I’ve felt remarkably more calm, and can get to bed by 10:30-11pm as of late.

There is a lot of tyrosine and tryptophan and other amino acids in there, and a strong link between mania/Schitzophrenia/catecholamines and tyrosine metabolism pathways. I need to read more, but it may be a clue. I have a genetic marker for increased risk of Schitzophrenia but I’m not reading too much into that as I’m sure23andme tells everyone they’re going to die of something.

But my neurotransmitters definitely been off my entire life, and a life of stress/depression could induce hypogonadism in the first place.

I may start taking isolated amino acid supplements and tracking their effect.

EDIT: Catecholamines cause general physiological changes that prepare the body for physical activity like the fight or flight response. Pasting from wikipedia sucks. Ok, so excess catecholamines in my body would lead to stress/sweating/high blood pressure all of which I have.

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A genetic defect in MAOA activity would mean my body cannot degrade catecholamines quickly enough. Drinking amino acid blends with precursors to catecholamines would lead to a build-up, and exagerated response of elevated catecholamine levels, like mania/psychosis/insomnia that I’ve been experiencing.

With chronic elevation in catecholamine levels, my receptors would down-regulate? Leading me to have constant impulsive behavior to get boosts of dopamine.

Starting TRT, my dopamine levels rose, impulsivity vanished overnight, and I felt happy for the first time in my life just existing. This was of course, short lived, as my receptors down-regulated even more?

I’ve been reading too much about hormones I need to read about some neurotransmitters.

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Hi Oppenheimer

Very interesting reading your thread.
I am now 45 and have had a lot of issues similar to yours and have done a vast amount of research over the last 20+ years.

My advice to you would be to look at 2 things immediately -

1/ ACROMEGALY

Get your IGF-1 tested and get an Oral Glucose Tolerance Test.

2/ Get full Thyroid bloodwork done.
TSH, T3, T4, RT3

I was first tested for Acromegaly at 22 but it was dismissed (I am 6ft6 with massive hands and feet). 22 years later I was tested and again IGF-1 was elevated and GH was not properly suppressed. (I am awaiting MRI etc)

I currently take 40mcg T3 daily and am on 125mg of Test once per week. It has taken about 2 years for my sexual function to come back to something like normal, running the same dose.

A couple of differences from you - I don’t sweat any more than average. I had no sexual dysfunction at all until late 30’s. I knew something was suddenly wrong and got an SHBG test done (95 odd). Obviously I am very high SHBG as opposed to you being low.

As an aside, I have had no hand or foot growth whatsoever in the last 30 years.

Don’t research everything, go through everything in stages, then rule out as you go.
You will get there in the end, but don’t expect the help of doctors - use your brain and your wallet.

Hope this helps and best of luck

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Appreciate it. One time my IGF-1 was low, one time it was high. The thing is there are cases of pseudoacromegaly or acromegaly where IGF-1 can be normal because insulin resistance can drop it down. I was definitely insulin resistance when I got that test done. So an OGTT to measure GH woulda been better. I’m in masscahusettes and I think we’re one of the states that doesn’t allow private bloodwork, or we weren’t last year when I checked.

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I am in MA as well and we DO allow private blood work and have for at least the last 3 years. Check health-tests-direct.com or ultalabtests.com. I usually find ulta to be slightly cheaper but it depends on the tests.

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Awesome thanks. I swore I checked one or two years ago and we were on the list with NY and NH as places they don’t allow personal testing. Happy to know I am wrong. Time to go nutty on lab work.

Ever know anyone that used https://www.menshealthboston.com/about-mhb/meet-our-team Dr. Morgentaler? I’ve watched a few talks of his and while I’m sure he makes a shitload of money, he seems to be personally interested in TRT and men’s health from a scientific perspective.

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I dont know anyone that uses him but for years he was the leader in progressive TRT. I do not think he is cheap. I researched him briefly before I got my PCP to agree to prescribe Test.

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Well, for anyone that cares, I do not have a pheochromocytoma based on 24 hour urine tests. Rapid heart rate, panic attacks, excessive sweating, high blood pressure, are I guess being caused by something else. This makes 0 sense. I took my injection yesterday, went to bed at 11pm, woke up at 6 am awake, laid down for 30 minutes while my laundry was drying, and woke up at 12 noon. I don’t understand why I have to sleep 14-15 hours every night. Something aint right.

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I’m sure you’ve researched narcolepsy.

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You haven’t really talked about thyroid. That tells me your doctor is not very well versed if he’s talking TSH. Anyone in the thyroid world knows TSH is a horrible marker to follow and trust …

Why don’t you think about a trial of armor thyroid . If you haven’t tested free t3 and reverse t3 you better. You don’t want it in range. You want free t3 top of range at your age. You want reverse t3 below 5. You don’t want to use TSH as a gauge.

Low thyroid caused me serious fatigue. Metabolism issues. Depression and so much more . I wouldn’t start thinking of serious disorders until this hormone has been optimized. Sounds like it could be the reason behind your aches and pains.

Trust me on this and go get tested. Find a doctor who actually understands this hormone and won’t give you synthetic crap or under dose you.

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Sounds like a thyroid problem man. Don’t over think it.

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I agree. I will try to find all the thyroid workups I had. My mother, grandmother, other grandmother, great grandmother, and 2 great-aunts, all have hypothyroid/had hypothyroid. Mother and grandmother are still on thyroid meds to bring their TSH down. I told my endo and doctor this but they said if my TSH is normal thyroid isn’t an issue.

Highest mine ever was 4.23 but on a range of 0.3-4.2 that’s a wide range. I don’t know if it’s telling that it dropped to 2.7 while on TRT, because I’ve lost about 80 pounds now. These are the only tests where T3, T4, and TSH were measured at the same time, back in 2016.

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I could have some wild ass viral inflammation caused by chicken pox when I was 5 which is when I started sweating. Going to Urologist to check on inflamed epidydimis. Bitten by dear tick 3 times, only given doxycycline once. I have Heberden’s Nodes on my fingers, which points to Rheumatoid Arthritis. Fuck if I know. No doctor actually takes a scientific method to rule things out besides basic cheap blood tests, then says here take testosterone for the rest of your life.

TRT has reduced inflammation a shit-load, I went from feeling puffy and swollen 24/7 to fine. I was missing doses past few weeks because I was anxious and kept stabbing myself and pulling the needle out. Once I took my dose yesterday I’m back to feeling great. Still can’t maintain erections but w/e for now.

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That’s textbook “sub clinical” hypothyroidism IMO. It’s worth a trial or thyroid meds to see what happens.

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Indeed, but plenty of other TSH levels that are normal. I think there is a congenital condition that caused something to go wrong with my hypothalamus. Crazy sleep patterns, sweating, thermal dysregulation, mood disorders, hypothalamus is the master regulator and I’ve never been in homeostatis my entire life.

My sister had early closure of the skull when she was a baby, a protruded lower jaw, widely spaced teeth, bicornuate uterus…and I have widley spaced teeth, prodtruded lower jaw, large nose, endocrine issues.

Something is F’ed with the way my face formed and my hypothalamus is shrekt which caused endocrine issues. Kallmann syndrome and normosmic congenital hypogonadotropic hypogonadism are usually associated with midline facial defects. My sisters condition is associated with FGFR2 mutations, FGFR1 mutations in men produce Kallmann syndrome or ncHH. The fact we both have issues indicative of an FGFR mutation is pretty telling I think.

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And I guess I’ve been looking for answers to remove the idiopathic, but my endocrinologist did diagnose me with normosmic idiopathic hypogonadotropic hypogonadism which according to literature, is a rare disease.

" Idiopathic hypogonadotropic hypogonadism (IHH) is a rare clinical disorder characterized by delayed or absent pubertal development (1). IHH has an incidence of 1-10 cases per 100,000 births and it is more common in males"

What a shitty genetic lottery hand to win.