Why did TRT work ... and then stop?

Therapeutic Efforts Pharmaceutical
#86

RecentQuitter : This is a good question.

I had this same experience.

I have been on trt 3 times.

1st time I started HCG before TRT. I felt not much at all when i started injecting TRT.

2rd time I started TRT alone. First week felt much better in terms of mood, appetite, outlook, vitality, energy, strength but no improvements in libido. It lasted 8 days then started feeling worse and had to lower dose.
I changed to test prop a few months later and was getting erections within 30 mins of injecting. For the first 3 injections. They were getting weaker every time. After the first 3 i felt nothing. Also after the first dose I felt VERY hungry within 1 hour. Probably due to insulin sensitivity improving.

3rd time. My pfs has got worse since the second time and felt not much.

I used to think this was all due to estrogens but then I did a lot of blood work on AIs and found that even when my e went down I felt no better.

So my current theory is this. When you first inject the T is released and your free T goes up but your shbg has not had time to change so suddenly you feel the T hitting your cells. Then as time goes on SHBG is decreased as it was in me now there must be a reason why SHBG is high in some of us in the first place, perhaps it is attempting to bind up some metabolite which is being produced in excess. So once we force the SHBG down whatever it was binding up becomes free and then acts strongly on our cells. This is my current theory.

FOr me DHT cream was similar. I took DHT cream felt improved mood and outlook and the next day I felt a lot worse. This was while on TRT so it was not simply T reducing T.

It is that or perhaps some T or DHT metabolite but I doubt that.

My saliva progesterone is way over range so perhaps that explain this. As SHBG decreases free progesterone or progesterone metabolites increase.

So I would question you, why is your SHBG high in the first place? For me my free T is low because of SHBG is it there trying to bind up something causing our problems?

Take a look at my saliva prog in the attached image. Saliva is only a measure of unbound hormones? Perhaps TRT further increased this problem?

Capture.JPG926×424 56.1 KB

#87

This is why I think TRT only works for a short time and some may even get worse.

J Steroid Biochem. 1985 Jul;23(1):33-8.
Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man.
Ruokonen A, Alén M, Bolton N, Vihko R.
Abstract

The influence of high doses of testosterone and anabolic steroids on testicular endocrine function and on circulating steroid binding proteins, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG), were investigated in power athletes for 26 weeks of steroid self-administration and for the following 16 weeks after drug withdrawal. Serum testosterone and androstenedione concentrations increased (P less than 0.05) but pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol, progesterone and 17-hydroxyprogesterone concentrations strongly decreased (P less than 0.001) during steroid administration. Serum pregnenolone, 17-hydroxypregnenolone and dehydroepiandrosterone sulphate concentrations followed the changes of the corresponding unconjugated steroids but 5-androstene-3 beta, 17 beta-diol and testosterone sulphate concentrations remained unchanged during the follow-up time. During drug administration SHBG concentrations decreased by about 80 to 90% and remained low even for the 16 weeks following steroid withdrawal. Steroid administration had no influence on serum CBG concentrations. In conclusion, self-administration of testosterone and anabolic steroids soon led to impairment of testicular endocrine function which was characterized by low concentrations of testosterone precursors, high ratios of testosterone to its precursor steroids and low SHBG concentrations. Decreased concentrations of SHBG and testicular steroids were still partly evident during the 16 weeks after drug withdrawal. The depressed circulating levels of dehydroepiandrosterone and its sulphate may indicate that the androgenic-anabolic steroids also suppress adrenal androgen production.

#88

Interesting, but I don’t think this meshes with my experience. My SHBG dropped when I started TRT – but this corresponded with feeling better. SHBG started to rise again as I stopped feeling the T. It’s very striking in my lab work over the last 3 years. The only time my SHBG dropped to a normal level was when I was feeling the T. So in my case, a drop in SHBG level was a good thing.

#89

My SHBG has remained pretty low/normal over my decade or so of PFS.

#90

That is strange. TRT is known to low SHBG. So how could it climb?

For me I have some blood work on TRT and it does lower my SHBG. That test was done when I lost the positive effects.

I feel the positive effect of trt for the first week. Starting the first day of first shot. I would have thought SHBG would not change that much in this time.

Have you tried just DHT cream? For me I got the same pattern. Felt somewhat better in terms of mood with the cream on the same day. The next day I was worse. And this is WHILE on TRT so T levels are stable.

DHT lowers SHBG to a greater degree and binds much more stronly with SHBG.

Have you tried quiting trt waiting a couple months and going on again?

#91

I only have 2 tests

SHBG on TRT
32(15 - 50) nmol/L

SHBG long time after quiting TRT.
44(15-50)nmol/l

My saliva hormones are messed up so for me I guess it does make sense as for others, I am not sure.

#92

In my case, my SHBG has consistently been at the top of the range or above. It was 47 (on a scale of 50) two weeks after I quit Propecia and it was 60 the last time I measured it. But when that first T shot actually worked for me at the end of 2012, it plummeted to 21. Then the T stopped working and within weeks it was back into the 40s, and it’s never come down sense. So I’ve always thought that for me, something about the T working lowered my SHBG. That said, when I talked about this with Dr. Goldstein in San Diego, he mostly shrugged and didn’t have much to say.

#93

I would question why shbg is so high to begin with at least in my case for some reason my saliva progesterone is very high. My shbg is probably binding some of this up. Hence if SHBG falls free progesterone would increase assuming it was being produced at the same rate when on TRT.

When I was on TRT i switched from test e to test p and again i got a boost. Within 30 minutes of injecting I would get a random errection. This never happens to me without TRT. But those effects only happened for the first T shot.

My guess is when T first entered the body it was free to bind to cell and cause a positive change but then after about a week some kind of secondary change was brought about by the TRT ie SHBG lowering which caused the effects of the T to be wiped out.

We do not all have the same hormone levels here so that could be why we react differently.

I found some more SHBG results

SHBG nmol/L (15-50)
32 TRT
46 No TRT
44 No TRT
45 No TRT

As you can see my SHBG was lower on shbg and is consistently higher without.

I would question how long it takes for the SHBG to fall. I have no blood tests on this matter.

How long after your first shot did you test your shbg?

Are you on TRT now? Did you try and quit for 6 months, go back on and see if the same thing happened?

#94

The test that showed my SHBG plummeting was taken about 3 weeks after the first shot. And I felt the effects of that shot on and off for about two weeks – so this blood test is the closest I’ve ever come to having a blood test while feeling normal, although it doesn’t sync up perfectly. I took another blood test two weeks later and SHBG was all the way back up into the 40s. It remained in the 40s for the next nine months while I stayed on T. I was then off T for about a year, and my SHBH remained high. I took another T shot last fall and SHBG clocked in at 60. We don’t seem to have the same thing going on.

#95

How long after your first shot did you feel the benefits of TRT? And how many days did those benefits last?

#96

I felt a clear libido boost about 36 hours in. It was unmistakable. I had this almost animalistic urge to get off and had no problem getting and keeping a real hard-on. A second wave hit me the next day, when the connection between my brain and dick came back completely. I didn’t have to concentrate or try hard or anything. A simple sexual thought or image triggered an immediate raging hard-on – just like the old days. I ended up jerking off a bunch of times that day. (This was a useful experience, because it reminded me exactly what it means to get my libido and sexual function back. I’ve had some better days and some worse days in the years since, but none of the good days have even begun to approach what I was able to do effortlessly when the T was working. I try to keep this in mind when gauging perceived “improvements.”)

After those first few days, it was a roller-coaster for two weeks. One day it would disappear completely and I’d be devastated…then the next day it would come roaring back, full force. It got to a point where I thought this might be my new normal – a few days on, a few days off. And given what I’d been through, I would have been OK with this. Full, normal sex function 50% of the time? Sign me up. Unfortunately, it stopped coming back after a little more than two weeks. It faded out one afternoon and I fully expected it to be back the next day…but it never returned. This was in November 2012.

I should add that a year later – December 2013 – I tried natural T-boosters and iodine. At the time, I’d been off T for months. It wasn’t as dramatic, but there was a very clear and vivid increase in desire/ability. But it vanished after about 36 hours and never came back, no matter how much I tried with natural T-boosters. And then in the last few weeks, I tried a combination of hydrocortisone and ERFA (thyroid medicine) based on some positive anecdotal reports on here. Again, I seemed to respond at first, but this time even less dramatically…and it’s also stopped working completely now, even after I upped the dosage.

Overall, it’s a pattern of diminishing returns. It’s like the more time that passes and the more I try, the less my body can handle or detect or whatever.

#97

Thank you for that. For my experience was a bit different. I had improved mood, appetite, vitality within 24 hours and that lasted about 8 days and then it was totally gone. I only ever improved my libido by anti estrogens. Which was like you describe.

You said your low SHBG was recorded after 3 weeks. Does this mean that when that test was done you had lost the benefits of TRT? Ie you have no SHBG test from when you were feeling recovered?

#98

That’s right. The benefits faded out on November 29 and the test was taken on December 4. It’s not ironclad, but it does suggest strongly that the fall in SHBG correlated with feeling better and the subsequent spike correlated with the end of T’s effectiveness.

I’d also add that in my case, mood and energy are not separate from libido and sex function. Yes, I have good and bad days mentally. But the good are never as good as a normal day used to be. For me, it’s a depression brought on by the fact that I have the sex drive/function of an 80-year-old, along with the physical changes to my body that has produced. When my sex drive returned in November '12, so did my mental state. I was ecstatic because I felt like I had my life back. I made a list of all the people I’d been putting off during what then had been six months of Propecia hell and began making plans to reconnect with them – to tell them about this bizarre, nightmare journey I’d been on and to get back to normal relationships with them. I remember that feeling. It’s what life felt like before Propecia, with an added sense of euphoric gratitude for getting a second chance. I have no doubt that all of that would return instantly if my sex function were to return.

#99

I agree that all symptoms are related. Fix one and you fix all. I have felt this. It makes PFS frustrating.

But I am not sure I agree about your assumption with SHBG. The fact is that you tested SHBG when you lost all benefits from TRT. If lowering SHBG was responsible for making you feel better on TRT you should have felt great when you did that test 3 weeks after, but you did not. So therefore lowering SHBG does not fix your problem.

As for what your shbg was for the first week or so on TRT we do not know at all. My assumption is shbg does not react instantly and takes a while to adjust. For me this is why I think it is implicated in the short term affects of TRT because when you start on T your T levels go up and your SHBG level do not change instantly. So there is an overlap as your shbg levels start to change TRT loses its effects.

First I thought it was estrogens but now I have done blood tests I do not think it is. Apart from shbg I do not know what it could be. Perhaps the build up of some kind of T metabolite which is not simply e2.
The question is why is SHBG high in the first place. Perhaps in our cause we have some kind of metabolite which is too high that the body is attempting to bind up.

#100

Not necessarily. What I know is that my SHBG level was much lower 3 weeks after I started taking T and that for 2 of those weeks I felt great (on and off). It had been 47 before the T shot and it was 21 after. Yes, the effectiveness had worn off by the time that test was taken putting it at 21…but who’s to say it wasn’t lower a week earlier, when the T was working? Again, I have tested my SHBG level about 15 times over the last 3+ years. It has been high every single time except for once – a test taken only a few days after I had felt a real impact from the T.

#101

Yeah also my two recoveries (full recoveries without TRT) with hCG + anastrozole and insulin lispro lasted about 8 days.
It seems not directly correlated with the 5 alpha reductase activity because half-life type 1 is 14 days and half-life type 2 is 30 days.

#102

It’s been a long time since anyone said something on this thread, I read the whole thread and basically it comes down to a big argument… well fine but it’s 4 years later and the original question still isn’t answered.

So for anyone who has a new theory on why TRT works for a short period of time pls share it.

#103

Perhaps you can summarise the main points of the topic so people can build on what’s come before, this place is full of repetition.

#104

Is it possible that your first T shot worked because your estrogen levels were high and the T stopped working because you were blocking estrogen with Arimidex? Check out this paper, the author is theorizing that our symptoms are actually caused by estrogen levels being too low. Lots of evidence in the paper to back up the theory.

[https://osf.io/jxnbu/] (PSSD,PFS,PRSD: A perspective for aetiology and treatment)

#105

This theory is written by a narcissistic (his nickame on reddit is sweaty_literature_69) person who claims to have cured PSSD by injecting estrogen levels higher than a transsexual wouldbe injected with. There was recently a thread on reddit of people who ended up badly for following this theory (in hospital).
It has 0 scientific basis. Later on there were people saying that sweaty charged €100 for coaching. Just another guru profiting.
As with everything else, if you have an oestrogen deficiency you will be better off if you fix it, but this theory is nonsense. Look up the scientific relevance of this “author”.

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