Done with TRT and recovered within two weeks

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readalot

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Defy Medical TRT clinic doctor

Mastodont

Active Member


That's good news, as i want more shbg :D
 

FunkOdyssey

Well-Known Member
You are right about the caffeine study. It shows correlation which can be explained in exactly the way you said, not necessarily that caffeine intake reduces testosterone.

That's why in statistics they say "correlation is not causation".
That's a good thing to keep in mind when thinking about caffeine. While caffeine and coffee consumption are associated with many health benefits in observational studies, these relationships don't appear to be causal:

Nutrients. 2018 Sep 20;10(10):1343.
doi: 10.3390/nu10101343.

Mendelian Randomization Studies of Coffee and Caffeine Consumption​

Marilyn C Cornelis 1, Marcus R Munafo 2

Abstract​

Habitual coffee and caffeine consumption has been reported to be associated with numerous health outcomes. This perspective focuses on Mendelian Randomization (MR) approaches for determining whether such associations are causal. Genetic instruments for coffee and caffeine consumption are described, along with key concepts of MR and particular challenges when applying this approach to studies of coffee and caffeine. To date, at least fifteen MR studies have investigated the causal role of coffee or caffeine use on risk of type 2 diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease, gout, osteoarthritis, cancers, sleep disturbances and other substance use. Most studies provide no consistent support for a causal role of coffee or caffeine on these health outcomes. Common study limitations include low statistical power, potential pleiotropy, and risk of collider bias. As a result, in many cases a causal role cannot confidently be ruled out. Conceptual challenges also arise from the different aspects of coffee and caffeine use captured by current genetic instruments. Nevertheless, with continued genome-wide searches for coffee and caffeine related loci along with advanced statistical methods and MR designs, MR promises to be a valuable approach to understanding the causal impact that coffee and caffeine have in human health.

Personally, I think it is likely that people who are able to tolerate caffeinated beverages at advanced ages are in better health than those who cannot. It may just be a stress test that identifies the weak.

With regard to testosterone, the authors of the NHANES 2013-2014 caffeine & testosterone study lay out many possible mechanisms in the discussion section:

There are several potential biological mechanisms underlying the associations observed between caffeine and testosterone. After ingestion, caffeine is known to exert various pharmacological effects at the cellular level [5]. Caffeine’s primary mechanism of action is antagonism of adenosine receptors, and acts on all four adenosine receptor subtypes in the brain (A1, A2a, A2b, A3) [34, 35]. In addition to those found in the brain, adenosine receptors have also been described in the testes [36]. Adenosine receptors observed in the testes are mainly localized within the Leydig and Sertoli cells of the seminiferous tubules, and these receptors are associated with an inhibition of cellular responses following activation. Following activation of these receptors, cAMP/protein kinase pathways, which are usually activated in mediation of testosterone production, are downregulated and may lead to lower testosterone production [3739]. It is possible that caffeine affects testosterone production through these adenosine-dependent pathways.

The findings of this study may also be relevant for early life exposure to caffeine, and long-term effects exposure may have on reproductive outcomes. Reproductive studies have begun to investigate the association between caffeine exposure and parameters of reproduction such as sperm quality, semen volume, and egg maturation. A previous by Dlugosz et. al found that doses of caffeine higher than 400 mg/day might decrease sperm motility and/or increase the percentage of dead spermatozoa, but not sufficiently to affect the male fertility in an adverse manner [40].Rats exposed to high doses of caffeine in utero developed smaller testes compared to controls [41]. This study also found that stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the high-dose caffeine rats. A Danish pregnancy cohort study found that men who were born to mothers drinking 4–7 cups/day of coffee had lower testosterone levels than sons of mothers drinking 0–3 cups/day [42, 43]. Furthermore, there was a significant, positive association between high caffeine intake and testosterone levels in the adult males. In addition to direct effects on the testes, caffeine has been shown in vitro to induce aberrant DNA methylation and histone acetylation of the steroidogenic factor-1 (SF-1) promoter in the rat fetal adrenals, which acts to reduce transcription of the SF-1 gene. SF-1 is a key transcription factor involved in transcription of genes related to steroidogenesis and testosterone biosynthesis in males, and reduced expression of SF-1 may be a mechanism of low testosterone related to caffeine.

In addition to caffeine, the metabolically active products of caffeine metabolism including theophylline and theobromine of the xanthine class have been shown to have direct effects on gonadotropin-induced steroidogenesis [44]. Mechanistically, theophylline and theobromine act as a phosphodiesterase inhibitors, adenosine receptor blockers, and histone deacetylase activators [45, 46]. In one study, various concentrations of theophylline and 1-methyl 3-isobutyl xanthine (MIX) significantly inhibited steroidogenesis. Additionally, higher concentrations of MIX and theophylline also significantly inhibited precursor incorporation into RNA and protein. In another study, Osborne-Mendel rats who were fed varying doses of caffeine, theophylline, and theobromine exhibited significant testicular atrophy and impaired steroidogenesis [47].Thus, in addition to direct effects of the parent compound caffeine, caffeine’s biologically active metabolites may also act through various pathways to affect testosterone production and half-life.

I do have two copies of the CYP1A2 "slow metabolizer" gene which would cause caffeine to have a longer half-life and would make me more susceptible to adverse effects as a result.
 

Mastodont

Active Member
My thinking on this would be biased due to my 70 year old dad being a hardcore coffee drinker and still having total t above midrange in the 700s, i guess old guys were built better, or were less exposed to chemicals and plastics in the womb and growing up
 

FunkOdyssey

Well-Known Member
My thinking on this would be biased due to my 70 year old dad being a hardcore coffee drinker and still having total t above midrange in the 700s, i guess old guys were built better, or were less exposed to chemicals and plastics in the womb and growing up
I would be suspicious with the age and coffee consumption that it's an SHBG-driven 700s total. Any SHBG or free T values for him? My total T is about the same off the coffee but my free T is 66% higher.
 

Mastodont

Active Member
I would be suspicious with the age and coffee consumption that it's an SHBG-driven 700s total. Any SHBG or free T values for him? My total T is about the same off the coffee but my free T is 66% higher.
So high shbg can actually increase testosterone production? I checked and yes the shbg was high(67).
Would also be interesting to have data on shbg and caffeine consumption in older males. Pretty sure there are elderly men with high shbg that don't drink coffee.
 
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Cataceous

Super Moderator
So high shbg can actually increase testosterone production? ...
Current thinking is that rising SHBG pushes up total testosterone without having much effect on free testosterone. The latter is tied to the production rate. SHBG might be thought of as a reservoir for testosterone. Increase the size of the reservoir and more total testosterone can be held, but this is pretty independent of the flow into and out of the reservoir—the flow rate being analogous to the production rate.
 

Mastodont

Active Member
My personal observations indicate that a high shbg male with decent total t is overall coping better with life than a low shbg low total t male such as myself.
 

Cataceous

Super Moderator
My personal observations indicate that a high shbg male with decent total t is overall coping better with life than a low shbg low total t male such as myself.
We'd want to ensure the two populations have comparable levels of free testosterone before going further. It does seem as though there are more complaints from guys with low SHBG. However, low SHBG correlates with some bad things, e.g. metabolic syndrome. It would be a job to separate out the confounding factors and show definitively that low SHBG by itself is causing significant issues. There is this one interesting case study concerning a man with undetectable SHBG. He was said to have "muscle weakness, fatigue, and a low libido", but "normal gonadal development and spermatogenesis".
 

GreenMachineX

Active Member
That's a good thing to keep in mind when thinking about caffeine. While caffeine and coffee consumption are associated with many health benefits in observational studies, these relationships don't appear to be causal:



Personally, I think it is likely that people who are able to tolerate caffeinated beverages at advanced ages are in better health than those who cannot. It may just be a stress test that identifies the weak.

With regard to testosterone, the authors of the NHANES 2013-2014 caffeine & testosterone study lay out many possible mechanisms in the discussion section:



I do have two copies of the CYP1A2 "slow metabolizer" gene which would cause caffeine to have a longer half-life and would make me more susceptible to adverse effects as a result.
Maybe those that need caffeine are the weak :)
 

Fortunate

Well-Known Member
I repeated my labs at 2.5 months since final test cypionate dose, 1.5 months since final test propionate dose, and 1 month since final enclomiphene dose:

Test

Pre-TRT Baseline

1 Month Post-PCT

Normal Range

LH

3.8 mIU/mL

3.9 mIU/mL

1.5 - 9.3 mIU/mL

FSH

10.5 mIU/mL

8.0 mIU/mL

1.6 - 8.0 mIU/mL

Total Testosterone

612 ng/dL

603 ng/dL

250 - 1100 ng/dL

SHBG

56 nmol/L

36 nmol/L

10 - 50 nmol/L

Free Testosterone (EqD)

66.7 pg/mL

111.0 pg/mL

35.0 - 155.0 pg/mL

Free Testosterone (calc)

8.7 ng/dL

12.5 ng/dL

4.6 - 22.4 ng/dL


My SHBG is normal now and my free T is much higher than before I started. The only thing different about my lifestyle is that I no longer consume caffeine after I was forced to give it up to tolerate TRT. Some research supports the idea that caffeine consumption can significantly reduce testosterone levels.


Thank you TRT, for overstimulating me to the point that I couldn't tolerate the caffeine anymore that was suppressing my testosterone production and making me think I needed TRT. I even found a use for my old vials of testosterone cypionate: I'm giving my wife roughly 5 mg a week now (3 mg every 4 days). I have a couple years supply at that dose. I'll talk about that more in the other thread.

My libido is still mediocre but otherwise I'm doing pretty well. I just read this book that I would recommend to everyone:

Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health—and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More

I'm focused on strategies to improve mitochondrial function now and trying some different things like doing more cardio, meditating more regularly, supplementing alpha lipoic acid and some b-vitamins, etc. I'll report back on how that goes.
Meditation has been really useful for me. Keep us up to date on how you are doing.
 

Cooper

Member
I'm about to go cold turkey off TRT. I've been on for 6 years or so, but no hcg. You didn't use clomid or anything? I might not use anything to come off except healthy diet. Why did you stop?
Interested to see your results as I am considering same thing after about 6 years and many different protocols. I have developed several issues I believe are related to my trt including sleep apnea.

Therefore thinking of stopping cold turkey or potentially trying testosterone cream first as I have heard that cream may be less likely to cause apnea than injections.
 

GreenMachineX

Active Member
Interested to see your results as I am considering same thing after about 6 years and many different protocols. I have developed several issues I believe are related to my trt including sleep apnea.

Therefore thinking of stopping cold turkey or potentially trying testosterone cream first as I have heard that cream may be less likely to cause apnea than injections.
Well, I haven't done it yet. I've been trying 5mg daily one more time, but looking at other reasons for my issues. Increasing my niacin and adjusting a couple other things for my sleep and other issues has actually been helping. I just find it hard to believe in my case that midrange testosterone and only 5mg per day was causing issues so I've looked at other things.
 
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