Ancedotes of feeling better when taking time off injections.. Science behind this?

[Tylurnt]

Ive experienced and have seen others who have had trouble dialing in, that take days or a week of their protocol and feel so much better.. Ive felt this myself and cant figure it out. Its not as simple as the dose being to high, because I took some days off then adjusted my dose down 25% and the good feeling slowly faded. Does anyone know the science behind this and whats actually going on? I just want to feel like i did when I took that time off

 

[Vince]

When you stop injections, your testosterone and estrogen levels may drop at a different percent. The ratio between testosterone and estrogen might reach an optimal balance that makes you feel great, as neither hormone is excessively high or low.

 

[Tylurnt]

When you stop injections, your testosterone and estrogen levels may drop at a different percent. The ratio between testosterone and estrogen might reach an optimal balance that makes you feel great, as neither hormone is excessively high or low.

Would testosterone drop first?

 

[Vince]

Would testosterone drop first?

That would make sense because estrogen follows testosterone.

 

[Phil Goodman]

Decided to see what ChatGPT would say in this topic… seems like reasonable hypothesis(and Vince already touched on one of them).

What’s likely happening (not just “dose too high”)​

1.​

When you stop injections for several days, serum testosterone drops faster than downstream neurosteroids (like allopregnanolone).

• Allopregnanolone strongly modulates GABA-A receptors
• This can temporarily:
  
  • Reduce anxiety
  • Improve sleep
  • Improve mood
  • Increase sense of calm / well-being

When TRT is restarted—even at a lower dose—neurosteroid balance shifts again and the effect fades.

Key point:
The “good feeling” is often a temporary CNS state, not a sustainable hormonal level.

---

2.​

Chronic steady exposure to exogenous testosterone may lead to:

• Reduced androgen receptor sensitivity in certain tissues (including CNS)
• Altered receptor signaling efficiency

A short break can temporarily:

• Increase receptor responsiveness
• Improve perceived effects even at lower serum levels

Once injections resume, receptors re-adapt and the effect disappears.

This explains why:

• A lower dose doesn’t recreate the feeling
• The benefit fades despite “better numbers”

---

3.​

Estradiol does not track testosterone in real time.

When you stop TRT:

• Testosterone drops quickly
• Estradiol often declines more slowly
• The T:E ratio temporarily improves

This can reduce:

• CNS overstimulation
• Water retention
• Mood volatility

When TRT restarts:

• Aromatization ramps back up
• The ratio normalizes (or overshoots), and symptoms return

This can happen even if estradiol labs look “normal.”

---

4.​

Some men on TRT experience:

• Elevated sympathetic nervous system tone
• Increased cortisol variability
• Poor stress tolerance

A short break can:

• Reduce adrenergic drive
• Improve sleep quality
• Lower resting cortisol output

This feels like:

“Calm, clear, energized, but not wired”

Restarting TRT restores the prior neuroendocrine environment.

---

5.​

Even with “reasonable” doses:

• Peaks may be higher than the person tolerates neurologically
• Troughs may still be high enough to suppress natural rhythm

Taking time off flattens peaks completely.
Lowering dose alone does not recreate that flat profile.

This is why some people improve with:

• Smaller, more frequent injections
• Or even transdermal delivery

---

Why lowering the dose didn’t recreate the feeling​

This is the key frustration point—and the answer matters.

Lowering the dose:

• Changes quantity
• Does not change:
  
  • Receptor signaling pattern
  • Neurosteroid timing
  • Estradiol kinetics
  • CNS adaptation

The “time off” effect is state-dependent, not dose-dependent.

 

[Phil Goodman]

@Tylurnt have you ever tried other delivery methods like cream or oral? If those are options it might be worth exploring to see if you have better luck. Also, do you take DHEA or pregnenolone? Lots of guys here include DHEA in their protocols, and it’s hit or miss with regard to pregnenolone… and I’ve seen people who can’t tolerate preg say that topical made large positive benefits in many areas. But as you can imagine from the difficulty of sustaining an optimal state from testosterone, adding in more hormones and/or supplements can often make it even more difficult to balance. But if you find something that works you can usually stick with it long term once your body settles in. I’ve been on 100-120 mg test/week, 750 ius HCG/week, and 12.5 mg DHEA daily from a hormonal perspective and that’s been my protocol for over 2 years with practically no issues and lots of good results.

 

[Tylurnt]

Decided to see what ChatGPT would say in this topic… seems like reasonable hypothesis(and Vince already touched on one of them).

What’s likely happening (not just “dose too high”)​

1.​

When you stop injections for several days, serum testosterone drops faster than downstream neurosteroids (like allopregnanolone).

• Allopregnanolone strongly modulates GABA-A receptors
• This can temporarily:
  • Reduce anxiety
  • Improve sleep
  • Improve mood
  • Increase sense of calm / well-being

When TRT is restarted—even at a lower dose—neurosteroid balance shifts again and the effect fades.

Key point:
The “good feeling” is often a temporary CNS state, not a sustainable hormonal level.

---

​

so the ration of T/E to neuro steroids matter? Even if you have the same level of pregnenolone, its more felt the lower the T/E is?

 

[Tylurnt]

@Tylurnt have you ever tried other delivery methods like cream or oral? If those are options it might be worth exploring to see if you have better luck. Also, do you take DHEA or pregnenolone? Lots of guys here include DHEA in their protocols, and it’s hit or miss with regard to pregnenolone… and I’ve seen people who can’t tolerate preg say that topical made large positive benefits in many areas. But as you can imagine from the difficulty of sustaining an optimal state from testosterone, adding in more hormones and/or supplements can often make it even more difficult to balance. But if you find something that works you can usually stick with it long term once your body settles in. I’ve been on 100-120 mg test/week, 750 ius HCG/week, and 12.5 mg DHEA daily from a hormonal perspective and that’s been my protocol for over 2 years with practically no issues and lots of good results.

Did troche for 5 months, thats what led me to injections. Shitty nurse practicioner and shitty protocol...troche once in morning.

Have not tried cream, just kinda scared to rapidly change my protocol and severly destabilize me... because I have no idea on how to convert injection dosage to cream to even be in the ball park of where to start.

Im not quite ready to give up on shots yet. Im doing 8mg daily IM now... 8 days now. Dont feel any better but I need to stick it out and see. If this doesnt work...last resort is to try less frequent injections.. like once or twice only. Ive only ever done 3x a week and EOD

 

[Tylurnt]

@Tylurnt have you ever tried other delivery methods like cream or oral? If those are options it might be worth exploring to see if you have better luck. Also, do you take DHEA or pregnenolone? Lots of guys here include DHEA in their protocols, and it’s hit or miss with regard to pregnenolone… and I’ve seen people who can’t tolerate preg say that topical made large positive benefits in many areas. But as you can imagine from the difficulty of sustaining an optimal state from testosterone, adding in more hormones and/or supplements can often make it even more difficult to balance. But if you find something that works you can usually stick with it long term once your body settles in. I’ve been on 100-120 mg test/week, 750 ius HCG/week, and 12.5 mg DHEA daily from a hormonal perspective and that’s been my protocol for over 2 years with practically no issues and lots of good results.

Did troche for 5 months, thats what led me to injections. Shitty nurse practicioner and shitty protocol...troche once in morning.

Have not tried cream, just kinda scared to rapidly change my protocol and severly destabilize me... because I have no idea on how to convert injection dosage to cream to even be in the ball park of where to start.

Im not quite ready to give up on shots yet. Im doing 8mg daily IM now... 8 days now. Dont feel any better but I need to stick it out and see. If this doesnt work...last resort is to try less frequent injections.. like once or twice only. Ive only ever done 3x a week and

Decided to see what ChatGPT would say in this topic… seems like reasonable hypothesis(and Vince already touched on one of them).

What’s likely happening (not just “dose too high”)​

1.​

When you stop injections for several days, serum testosterone drops faster than downstream neurosteroids (like allopregnanolone).

• Allopregnanolone strongly modulates GABA-A receptors
• This can temporarily:
  • Reduce anxiety
  • Improve sleep
  • Improve mood
  • Increase sense of calm / well-being

When TRT is restarted—even at a lower dose—neurosteroid balance shifts again and the effect fades.

Key point:
The “good feeling” is often a temporary CNS state, not a sustainable hormonal level.

---

2.​

Chronic steady exposure to exogenous testosterone may lead to:

• Reduced androgen receptor sensitivity in certain tissues (including CNS)
• Altered receptor signaling efficiency

A short break can temporarily:

• Increase receptor responsiveness
• Improve perceived effects even at lower serum levels

Once injections resume, receptors re-adapt and the effect disappears.

This explains why:

• A lower dose doesn’t recreate the feeling
• The benefit fades despite “better numbers”

---

3.​

Estradiol does not track testosterone in real time.

When you stop TRT:

• Testosterone drops quickly
• Estradiol often declines more slowly
• The T:E ratio temporarily improves

This can reduce:

• CNS overstimulation
• Water retention
• Mood volatility

When TRT restarts:

• Aromatization ramps back up
• The ratio normalizes (or overshoots), and symptoms return

This can happen even if estradiol labs look “normal.”

---

4.​

Some men on TRT experience:

• Elevated sympathetic nervous system tone
• Increased cortisol variability
• Poor stress tolerance

A short break can:

• Reduce adrenergic drive
• Improve sleep quality
• Lower resting cortisol output

This feels like:


Restarting TRT restores the prior neuroendocrine environment.

---

5.​

Even with “reasonable” doses:

• Peaks may be higher than the person tolerates neurologically
• Troughs may still be high enough to suppress natural rhythm

Taking time off flattens peaks completely.
Lowering dose alone does not recreate that flat profile.

This is why some people improve with:

• Smaller, more frequent injections
• Or even transdermal delivery

---

Why lowering the dose didn’t recreate the feeling​

This is the key frustration point—and the answer matters.

Lowering the dose:

• Changes quantity
• Does not change:
  • Receptor signaling pattern
  • Neurosteroid timing
  • Estradiol kinetics
  • CNS adaptation

The “time off” effect is state-dependent, not dose-dependent.

Its also saying that I must feel better with a higher E2 to T ratio? Thats interesting