Long Term Users- Does Exogenous T Lose Its Efficacy?

BBaller

New Member
A concern some have voiced is that long term HRT may lose its efficacy. That users may have a honeymoon period, maybe lasting years, but over time, responsiveness to T or other hormones may diminish, and that a "tolerance" of sorts builds up, and that dosages may need to be continually increased to maintain the same effect. And then consequently, these increased dosages may present further complications for patients.

My questions are:
- Is there any evidence that this is the case?
- If these is such evidence, could that be attributable just to natural age related decline, and the need for increasing exogenous quantities to compensate? Or is that not really the case, as endogenous production basically halts anyway whenever supplemental T is utilized?
- Long term users: do you find that your treatment is less effective, or has it been possible to find a stable protocol that keeps you at baseline?
- I remember hearing of a report recently released about long term improvement in health outcomes for TRT users. Can anyone provide more information or links to that? Are there any other studies that show long term results for average TRT patients?

Aside from reduced fertility, perhaps my main hesitation is about becoming a 'guinea pig' and subjecting myself to possible unknown side effects down the line. I know some of the men here, including Nelson, have been using TRT for decades, and would love input from anyone in that position, especially since I am considering a more or less lifelong commitment.

Thanks in advance.
 
I've never seen anything that says a man would be tolerant to long term androgen use.

There may be need to adjust dosages over time to maintain the same serum levels...things like that...but I don't ever recall any scientific study that supports a tolerance to the drug under long term use.

Does the body in the natural state become tolerant to endogenous testosterone?
 
My questions are:
- Is there any evidence that this is the case?
- If these is such evidence, could that be attributable just to natural age related decline, and the need for increasing exogenous quantities to compensate? Or is that not really the case, as endogenous production basically halts anyway whenever supplemental T is utilized?
- Long term users: do you find that your treatment is less effective, or has it been possible to find a stable protocol that keeps you at baseline?
- I remember hearing of a report recently released about long term improvement in health outcomes for TRT users. Can anyone provide more information or links to that? Are there any other studies that show long term results for average TRT patients?

Aside from reduced fertility, perhaps my main hesitation is about becoming a 'guinea pig' and subjecting myself to possible unknown side effects down the line. I know some of the men here, including Nelson, have been using TRT for decades, and would love input from anyone in that position, especially since I am considering a more or less lifelong commitment.

Thanks in advance.


I have been on testosterone since 1992. I have taken every single form available in the US and abroad.

My libido was through the roof for the first few years, but I was also in my 20's.

I have attempted to stop TRT with clomiphene, hcg, etc but felt like crap. No use to get off since I still feel mental focus and all the other beenfits. I brought in hCG 5 years ago and it boosted my libido to this day.
 

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TRT Hormone Predictor

Predict estradiol, DHT, and free testosterone levels based on total testosterone

⚠️ Medical Disclaimer

This tool provides predictions based on statistical models and should NOT replace professional medical advice. Always consult with your healthcare provider before making any changes to your TRT protocol.

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Understanding Your Hormones

Estradiol (E2)

A form of estrogen produced from testosterone. Important for bone health, mood, and libido. Too high can cause side effects; too low can affect well-being.

DHT

Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth, prostate health, and masculinization effects.

Free Testosterone

The biologically active form of testosterone not bound to proteins. Directly available for cellular uptake and biological effects.

Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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