Agetron
#101
Agreed Jay, I am pulsing TRT at halfway point of rapamycin - 3 days post dosing.
Been doing almost 4.5 years… great results.
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Makes sense as the lean muscle gains made on rapamycin are in recovery, so giving something to stimulate that recovery, such as testosterone seems like a reasonable plan mechanistically.
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If you’re going to the aggravation of injecting yourself every week, you might as well aim for the higher end of normal or just above normal - maybe 1,000 to 1,200 ng/dl. Why do this just to feel “ok” - do it in order to feel GREAT. Just my $0.02 from being on TRT for a while.
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Agetron
#104
Exactly… lol.
Weekly injection of 200 mg or 1 ml… cypionate puts me at 1380 ng/mL. Amazing!!
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The justification I have for going for middle of the range (assuming you get symptom relief) rather than the high end/over the high end is reducing the risk of long term side effects. Eg. high blood pressure, high red count, CVD risk, hormone dependent cancers etc. Pushing your testosterone to 1000+ ng/dl (and depending on when you test it may peak substantially higher than that) is like souping up your car. Short to medium term it drives better but the wear and tear can be greater.
I’m coming from a lifespan perspective though.
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Was this your baseline when you were younger? Is the idea to supplement T back to youthful levels but not higher? That seems like a big number but maybe you were very high in your youth.
I didn’t get a T test until late so I don’t know my baseline. My total T has varied between 200-450 over the last 5 years. This is too low and has been impervious to improvement efforts. Oddly my estrogen is high so I’m converting too much T—>E despite low body fat and vigorous resistance training. I’ve recently added DIM to my stack to address. Perhaps I’m chronically over-trained.
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Agetron
#107
My youthful testosterone up to late 30’s was 900 to 1100.
So higher… normal. Feel great.
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Agetron
#108
Have you considered anastrazole? I take 1 mg with each shot… past 5 years.
TRT can increase testosterone levels, which can also lead to increased estrogen production. Anastrozole inhibits the conversion of testosterone to estrogen, helping to maintain a balanced hormonal profile.
I started TRT at age 61 years… began 1st year without anastrazole. Have used anastrazole for past 5 years… It has been 6 full years now.
No issues.
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I’ve heard of it. I’ll have to stick with OTC solutions for now but I’ll see if I can import it. Thanks
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Before I went on TRT, I discussed exactly those concerns with my doc, and he assured me that the 1000-1200 would not trigger those adverse side effects. In addition, I monitor my BP and my red count. It’s the guys on anabolic steroids who are souping up their car not the guys doing TRT.
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Is this a longevity or otherwise well informed doctor? I don’t have any well informed doctors helping me (cardiologist, urologist, GP, dermatologist). I value their advice in a narrow band but have given up trying to discuss options or cross domain issues. Partly they do not know, and partly they do not value my opinion, and partly they do not have time to “discuss”….is what I have concluded. Oh well, it is what it is.
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Agetron
#112
Exactly… I work at a medical school… great dedicated… smart physicians I have known for decades.
I am very surprised how little they know about longevity… TRT…HGH… osteoporosi … rapamycin… many eat well, excercise some and figure aging and functional declines are the normal process.
As a visual exception to my age… typically 5 to
10 years older then they are… but looking better and stronger… a number of them ask me about rapamyacin, taurine and my health protocols.
Once they get the nudge… they figure it out quickly. Doesn’t take them long to get a prescription of rapamycin.
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PBJ
#113
Testosterone Levels, Androgen Receptors, and the Role of Estrogen
Testosterone levels vary widely due to genetics. Your 450 ng/dL could be functionally equivalent to someone else’s 800 ng/dL, depending on androgen receptor (AR) density and sensitivity.
Using an aromatase inhibitor (AI) is generally a bad idea unless medically necessary. Studies suggest that testosterone replacement therapy (TRT) at normal physiological levels (≤1000 ng/dL) is safe, but higher levels—or the addition of an AI—can be neurotoxic. High androgens combined with low estrogen are toxic to multiple organs, which may help explain why men suffer from heart and kidney disease more than women.
If estrogen management is necessary, DIM and Calcium D-Glucarate are over-the-counter options that can help mildly lower estrogen. However, if you’re on finasteride, be aware that it can increase estrogen levels by reducing DHT.
Do Men with Lower Testosterone Have More Androgen Receptors?
Men with lower normal testosterone levels may have more androgen receptors (ARs) or increased receptor sensitivity as a compensatory mechanism. This is supported by several key principles of endocrinology and androgen physiology:
1. Androgen Receptor Density & Sensitivity Adjust to Hormone Levels
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Upregulation: When testosterone is low or on the lower end of normal, the body may increase AR expression to maintain androgenic effects.
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Downregulation: When testosterone is high (supraphysiological), AR expression often decreases to prevent excessive androgen signaling.
Example:
- A man with 400 ng/dL testosterone but high AR density could experience similar androgenic effects as someone with 800 ng/dL but fewer receptors.
- This explains why some men with “low-normal” testosterone levels feel great, while others with mid-range or even high testosterone experience symptoms of low androgens.
2. Genetic Differences in AR Sensitivity (CAG Repeat Length in the AR Gene)
- The AR gene contains CAG repeats, which influence androgen sensitivity:
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Shorter CAG repeats → Higher AR sensitivity (stronger androgenic effects at lower testosterone levels).
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Longer CAG repeats → Lower AR sensitivity (requires more testosterone to achieve the same effects).
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European men tend to have shorter CAG repeats than men of African or Asian descent, contributing to population differences in testosterone requirements.
3. Free Testosterone vs. Total Testosterone
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Total testosterone alone doesn’t tell the whole story—what matters is how much free testosterone is available to bind to receptors.
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SHBG (Sex Hormone-Binding Globulin) plays a role:
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High SHBG → Less free T, less receptor activation.
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Low SHBG → More free T, more receptor activation.
4. Why Some Men with High Testosterone Still Feel “Low T” Symptoms
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AR Downregulation: Extremely high testosterone (e.g., 2,500 ng/dL from exogenous sources) can downregulate ARs, making the body less responsive to androgens.
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Poor AR Function: Some men with high T but long CAG repeats may still experience low testosterone symptoms despite their high blood levels.
Conclusion
- Men with lower normal testosterone levels may compensate with increased receptor density or sensitivity.
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Genetics (CAG repeat length) plays a major role in how individuals respond to testosterone.
- Total testosterone alone does not determine androgenic effects—receptor density, SHBG, and free testosterone also matter.
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PBJ
#114
There are zero studies showing that TRT at 1000-1200 is safe.
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Urologist. Haven’t discussed rapa with him though.
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Tim
#117
Individual responses vary greatly, as do medical opinions. I recently turned 77. At 5’9 and 140 pounds, I have determined that a daily application of gel is too much for me, with such side-effects as acne and higher levels of BP. I have started to dial it down to once or twice a week. All I need is a little boost, not a big push.
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