T Nation

Does TRT Lose Effectiveness Over Time?


Long time lurker/first time poster here.

I started my TRT journey 3 years ago strictly abiding the “TRT Protocols” set forth by KSman. I personally wanted to say thank you. I was lucky enough to find a doctor who was willing to go about TRT the proper way, and things have been going smoothly ever since.

I did however have a question about long term TRT usage. I’m 29 years old and I do not foresee myself ever wanting to stop TRT simply due to the fact that my quality of life is exponentially better than when I first started. My question is this: over time, will you notice a decreased response to TRT? (I’m thinking along the lines of building up a “tolerance” or frying your receptors.)

I apologize for the newbie question, but I was looking for a similar thread but could not find one.

Any input/comments/insight would be greatly appreciated. Cheers.


No. Not going to happen.


I’m no expert but I’ve talked with my doctor multiple times about this same concern. He has assured me it won’t. Adjustments may be necessary (his words, not mine) but it won’t stop working. I want to ask, ‘yeah, but how about when I’m 90?’ Then I remember the damage I did to myself 18-35 and realize this is probably something I don’t need to worry about.

Edit: I’ll also add that I’ve been on for 5 years and I think it has become more effective the last two years. Almost the older I get, the more benefit. Not sure if this is in my head, but I honestly feel even better at 40 then 30.


Thanks for the reply. What your doctor said makes sense given the fact that natural aging processes will need to be counteracted with changes in TRT regiments.

I have an appointment with my doctor next month and I’ll be sure to pick their brain about this. I’ll repost in this thread if I find out anything useful.


Thanks for the reply. Cheers.


After 11 years of TRT, 68YO soon, it is impossible to separate things from the effects of aging. Do not expect things to be always steady. I have needed to increase T amounts to compensate, but that can only go so far. As you get older, the effects of non-optimal cortisol, thyroid and other things have a greater effect. A younger body can absorb non-optimal issues easier than an older one. All hormone systems need to be working well.

T and E2
thyroid - iodine - body temperatures
Vit-D3 and Vit-D25 labs. Vit_D25 is a critical hormone

Those are the big five. Keep those in good shape, and assuming one does not get other diseases of aging you will do well. Don’t abuse your body.

Please read the stickies found here: About the T Replacement Category

  • advice for new guys
  • things that damage your hormones
  • protocol for injections
  • finding a TRT doc

Evaluate your overall thyroid function by checking oral body temperatures as per the thyroid basics sticky. Thyroid hormone fT3 is what gets the job done and it regulates mitochondrial activity, the source of ATP which is the universal currency of cellular energy. This is part of the body’s temperature control loop. This can get messed up if you are iodine deficient. In many countries, you need to be using iodized salt. Other countries add iodine to dairy or bread.


I don’t “feel” like I did that first year on TRT, but I think its because I went from low to normal and it made me feel energized. I think I don’t have the same “bounce in my step” just because I’ve gotten used to having normal T.


How does a receptor get fried?


Probably a reference to things unknown. Cell wall permeability can be affected by diet and choice of fats, affecting all cell wall receptors. Cellular function that supports receptor cascades is subject to aging, cellular senility and inflammation. Other hormones are supportive: GH, fT3, Vit-D3, cortisol and CoQ10 etc. A classic receptor failure example is insulin resistance, aka type II diabetes. Vit-D25 and steroid hormones are effective in cell nuclei where DNA expression is affected. fT3 acts on mitochondria that make the cells energy ATP and that requires CoQ10 that is made in the liver and that can be decreased in some people by statin drugs. So many interconnected negative effects are possible.

And do not forget that energy levels, wellness, vitality, sexual function and libido are all perceptions in the brain. Brain rules or ruins everything.


KSman, thanks for the informative reply.

I think my biggest issue right now is battling cortisol levels. I’m due for blood work next week so I’ll be interested to see where I stand on that marker. I’m a chemist and have been putting in long hours at work lately - I think the added stress is causing my cortisol levels to increase. I guess I’ll find out soon here.



There is a pattern of stress response where one’s cortisol is increasing, but with progress into adrenal fatigue, cortisol levels are dropping. This creates a problem where you do not know what side of the hill your are one by looking at lab results, but if familiar with things, you would certainly feel what side of the hill you are on. But that is 20:20 hindsight as people have no idea what is happening, and to make matters worse, thyroid function gets messed up with T3, or iodine deficiency and/or low-T has been a contributing stress factor. Things get messy. Way too complex for most doctors who will reach for SSRI’s or diagnose fibromyalgia because they can claim that they do not know how to treat that so they can get you out of their office, because your labs are normal. <end of today’s rant>