Post TRT - Libido is DEAD :(

[Phil Goodman]

Your choice of what to focus on says it all. You are willfully ignoring the bigger picture about which approach to dosing benefits the most men with the least harm. Instead of providing actual evidence that being out-of-range is better you'd rather we debate minutia over the interpretation of the guidelines of one association, which still contradict you with their call for in-range levels.

I’ve already provided evidence that being out of range is better as shown by the studies that directly compared various doses. The group on the dose of 100-125 saw more benefits. Their risk was minimal. The risk would be even lower if they split the dose further (into 2-3 injections per week).


You have not provided any evidence that contradicts that. You’ve simply provided general guidelines of a range to land in…. guidelines that the medical association themselves label as being low priority as well as admitting there is weak evidence for the guideline provided. And even then they (a very conservative organization with regard to trt) suggest not falling below around 400. Which your recommended dose of 25 mg twice per week leaves patients under 400 for lots of time.

Secondly, the response can vary widely between patients. You are basing your entire argument on general (weak I might add) guidelines about where patients should fall without any supporting evidence. But since you refuse to provide studies, I went ahead and asked Grok. Let’s see where patients land on various doses, then let’s see if we can find a common ground to put this to bed. We both agree (I think) that 75 mg/week is ok for a starting dose. I tend to think many (perhaps most) patients would probably titrate up slightly from that dose whereas you may think they would probably go down. Either way, let’s just say 75 is a reasonable starting dose if we can agree on that.


AI warning below (Grok)… feel free to highlight any inaccuracies if you see any.


Here is a clear, evidence-based summary of serum testosterone levels achieved at various TRT doses, drawn from multiple peer-reviewed dose-response and pharmacokinetic (PK) studies. I analyzed key papers (Bhasin 2001 & 2006, Kaminetsky 2015, Xyosted phase 3 data/FDA label, and pharmacology reviews) plus supporting data on traditional IM injections and gels for context.


Important caveats before the data:


• Measurement timing matters: “Nadir” or “trough” = lowest level just before next dose (most relevant for weekly dosing). “Cavg” = time-averaged over the week. Peaks occur 1–2 days post-injection.


• Population differences: Fully suppressed young men (GnRH agonist + exogenous T) achieve lower levels than real hypogonadal TRT patients (partial endogenous production remains). Older men achieve higher levels at the same dose due to slower clearance.


• Route/frequency: Weekly split or SC injections produce flatter curves (less fluctuation) than biweekly IM. Individual factors (SHBG, body weight, metabolism, injection site) cause wide variability (±100–300 ng/dL common).


• Normal reference range: ~300–1,100 ng/dL (most labs). Guidelines (AUA/Endocrine Society) target mid-normal (~450–600 or 400–700 ng/dL) via titration.


• 50 mg/week is often borderline low; 75–100 mg/week reliably hits the target for most men; higher doses frequently exceed it.


Summary Table: Typical Serum Total Testosterone Levels by Weekly Dose





| Weekly Dose (TE or TC) | Study / Population | Typical Serum Total T (ng/dL) | Type | Notes |


|------------------------|-------------------------------------|----------------------------------------|---------------|-------|


| 50 mg | Bhasin 2001 (young suppressed men) | 306 (nadir) | IM weekly | Borderline low; often insufficient |


| 50 mg | Kaminetsky 2015 (hypogonadal men) | 422 (steady-state average) | SC weekly | Low-normal; many need titration up |


| 50 mg | Xyosted PK data | 458–598 (Cavg); trough ~458 | SC weekly | On low end for many men |


| 75 mg | Xyosted (starting dose) | 431–538 (Cavg); trough target 350–650 | SC weekly | Designed for physiologic range |


| 75–100 mg | General IM/SC reviews + real-world | 500–800 (trough/avg) | Weekly (split preferred) | Reliably mid-normal for most |


| 100 mg | Kaminetsky 2015 | 895 (steady-state average) | SC weekly | Solid mid-to-high normal |


| 100 mg | Xyosted pooled data | 553 (Cavg); trough ~436 | SC weekly | Within normal range |


| 125 mg | Bhasin 2001 (young) | 542 (nadir) | IM weekly | Mid-normal; anabolic benefits begin |


| 125 mg | Bhasin 2006 (older) | 852 (nadir) | IM weekly | High-normal in older men |


| 150–200 mg (or 200 mg every 2 weeks) | Traditional IM reviews | Peaks >1



Gel examples (for completeness, daily topical):


• 50 mg/day (≈5 g 1% gel): Cavg often 400–600 ng/dL (variable absorption).


• 100 mg/day: Cavg up to ~800–1,000+ ng/dL in some studies.


Key Analysis & Takeaways


• 50 mg/week consistently lands in the low-normal or borderline range (250–450 ng/dL average/trough) across studies — often too low for optimal symptom relief in real hypogonadal men (exactly as the fat-gain study referenced in prior discussion showed).


• 75–100 mg/week (the Endocrine Society/AUA practical starting range) reliably produces mid-normal levels (roughly 450–700 ng/dL trough or average) for the majority of men when dosed weekly or split 2–3×. This is the “sweet spot” for most: physiologic restoration without routine supraphysiologic exposure.


• Higher doses (125+ mg/week) push many men into high-normal or supra territory, especially older men or with frequent dosing. Benefits (muscle, IGF-1) continue dose-dependently, but so do risks (hematocrit rise, lipids, etc.).


• SC vs IM: SC (e.g., Xyosted) gives flatter curves and more predictable troughs in the 350–650 ng/dL target with less fluctuation than traditional biweekly IM.


• Variability is the rule: Some men need only 50–60 mg split; others need 120–150 mg to hit the same mid-normal bloodwork. Always measure trough (day 7 for weekly) at steady state (week 4–6), not random or peak levels.


This data strongly supports the guidelines: Start at 75–100 mg/week (split for stability), titrate based on actual bloodwork and symptoms to mid-normal range, and avoid blanket high dosing.

 

[Cataceous]

Let's just cut to the bottom line, shall we?

Query to Grok:
Regarding men starting testosterone replacement therapy, is there any scientific evidence to support the claim that it is better for overall health when initial doses lead to serum testosterone levels that are often or constantly above the normal range than when doses are selected to maintain serum testosterone around mid levels in the normal range?

Answer:
No, there is no scientific evidence supporting the claim that initial doses leading to serum testosterone levels often or constantly above the normal range (supraphysiological, e.g., median ~1,500+ ng/dL) provide better overall health outcomes than doses targeting mid-normal physiological levels (typically 450–600 ng/dL) in men starting TRT for hypogonadism.

Major clinical guidelines (Endocrine Society 2018; American Urological Association 2018/2024) explicitly recommend adjusting TRT to achieve and maintain mid-normal range levels, accompanied by symptom improvement. This is defined as the middle tertile of the reference range for most labs (~450–600 ng/dL). Success is not measured by exceeding the upper limit of normal.

Large trials and meta-analyses (e.g., the Testosterone Trials/TTrials in older hypogonadal men, TRAVERSE trial on CV safety) targeted and achieved mid-normal levels and demonstrated clear benefits in key health domains—sexual function, lean body mass, anemia correction, bone density (spine/hip volumetric), and modest mood/depressive symptom improvements—without excess risks when levels stayed physiological. No arm of these trials tested or showed superior outcomes from pushing levels supraphysiologically.

Direct or indirect comparisons of levels:

• A 2024 retrospective study (n=184 hypogonadal men on TRT) directly compared physiological (median 468 ng/dL) vs. supraphysiological (median 1,552 ng/dL) groups. The supra group had significantly higher polycythemia (35% vs. 7%), a known risk factor for thrombosis and cardiovascular events, but no differences in major adverse cardiovascular events (MACE), VTE, MI, stroke, or DVT. It reported no efficacy advantages for supra levels.
• Dose-response data (e.g., Bhasin et al.) in eugonadal men show greater muscle gains at supraphysiological doses short-term, but this is not TRT for hypogonadism, does not translate to overall health (e.g., no added long-term CV/mortality benefit), and increases side effects (lower HDL, higher hematocrit, potential cardiac remodeling).
• Meta-analyses of TRT (physiological dosing) confirm benefits vs. placebo in sexual function, lean mass, and some mood outcomes, with no additional proven health gains from higher dosing and clear dose-dependent rise in erythrocytosis.
• Endogenous testosterone observational data (e.g., Yeap et al.) link mid-range levels to the lowest all-cause and cardiovascular mortality in older men; both very low and very high levels carry higher risk.

Supraphysiological peaks (common with some injectable formulations) or sustained supra levels are associated with increased risks of erythrocytosis/polycythemia, potential estradiol elevation, and, in extreme cases (e.g., anabolic steroid misuse), adverse cardiac effects—without offsetting gains in hard health endpoints like mortality, CV events, bone fracture risk, or overall quality of life beyond what mid-normal achieves.

Subjective reports (e.g., some men feeling “better” at higher levels) exist but are not corroborated by objective health outcomes in controlled data and do not constitute evidence for better overall health. Guidelines and reviews emphasize that TRT corrects deficiency to physiological levels; it is not intended to create supraphysiological benefits.

In summary, the scientific consensus—based on guidelines, RCTs (TTrials, etc.), meta-analyses, and safety data—supports targeting mid-normal range for the optimal balance of benefits and minimized risks. There are no robust head-to-head trials showing superior overall health with supraphysiological levels; available evidence either shows equivalence (with added side-effect burden) or favors physiological targeting. Individualized monitoring (symptoms + labs every 3–6 months initially) remains key, but exceeding the normal range is not evidence-based for better health. Consult an endocrinologist or urologist for personalized advice.

 

[Phil Goodman]

@Cataceous …. As usual you provide exactly ZERO evidence to discredit the things I posted. I laid it out as plainly as I could, provided extensive hard evidence based on numerous studies, and even tried to find a common ground we could agree on.


Your response?? To blatantly lead a LLM with a vague question about whether it’s better to have levels constantly above the normal range or to have them in the normal range. To which it replied it’s worse to have them over 1500 then it is to have them between 450-600.



Not a single dose was mentioned in the response… just concerns with running excessively high levels. Sure, I agree that running levels over 1500 isn’t the best approach, so congratulations on that I guess?? Not sure what you expect me to say about that. I’m also not sure how that has anything to do with my post right above that one.

 

[Phil Goodman]

Also… @Cataceous i decided to go ahead and ask the same question to see the response and then follow it up with a question about dose. I used the exact same prompt you used above. The output was extremely similar and even identical in some areas. Then I followed up with this prompt.


What is a good starting dose for trt to achieve the desired levels?



A good starting dose for testosterone replacement therapy (TRT) is one that aims for mid-normal serum testosterone levels (roughly the middle tertile of the lab reference range, often ~450–700 ng/dL or 15–24 nmol/L, depending on the assay), individualized based on the formulation, patient factors (age, SHBG, metabolism, symptoms), and close monitoring.


Guidelines from the American Urological Association (AUA) and Endocrine Society emphasize starting conservatively and titrating to symptoms plus blood levels in the mid-normal range—not supra-physiological peaks. There is no universal “one-size-fits-all” dose, as absorption, clearance, and response vary. Always confirm hypogonadism diagnosis (two morning total T <300 ng/dL plus symptoms) before starting, and work with a clinician for labs, hematocrit, PSA, and symptom tracking.


Common Starting Doses by Formulation


These are typical evidence-based starting points (drawn from guidelines, FDA labeling, and trials like TRAVERSE). Titrate after 3–6 weeks (gels) or one injection cycle (injectables) based on trough or timed levels.


• Transdermal Gels (preferred for steady levels, easier titration, lower peak/trough swings):


• AndroGel 1%: 50 mg (one packet or equivalent) once daily (shoulders/upper arms).


• AndroGel 1.62%: 40.5 mg (two pump actuations) once daily.


• Testim/Vogelxo 1%: 50 mg (one tube) once daily.


• Fortesta 2%: 40 mg (four pump actuations) to thighs once daily.


• Others (Tostran/Testavan): ~40–60 mg testosterone equivalent daily.


• Measure levels 2–8 hours after application (after ≥1 week steady use); adjust up/down by one pump/packet as needed. In TRAVERSE, 1.62% gel was titrated to 350–750 ng/dL.


• Injectable Testosterone (Cypionate or Enanthate, most common and cost-effective):


• 75–100 mg intramuscular (IM) or subcutaneous (SC) weekly (preferred over larger less-frequent doses to minimize peaks/troughs and side effects like polycythemia).


• Alternative: 150–200 mg every 2 weeks (older approach, less ideal).


• AUA example: Start with 100 mg weekly rather than 200 mg every 2 weeks.


• Measure levels ~1 week after injection (mid-cycle or trough); target 400–700 ng/dL and adjust frequency/dose. Smaller, more frequent doses (e.g., 80–120 mg/week split) often yield more stable levels.


• Long-Acting Injectable (Testosterone Undecanoate, e.g., Aveed):


• 750 mg IM at weeks 0 and 4, then every 10 weeks (clinic-administered). Not for initial self-start due to loading schedule







Each time you double down you’re just making it harder for yourself to admit you might be wrong on this one… but the sooner you do you’ll probably feel a little lighter with this off your shoulders. It’s ok to be wrong, everyone is wrong from time to time.

 

[Cataceous]

How sad that you cannot acknowledge basic logic:

There's no evidence that above-range dosing is beneficial to overall health. There is evidence that above-range dosing is harmful to overall health. Dosing with 100 mg TC/week results in above-range levels in most men. Therefore do not start TRT with >= 100 mg TC/week.

So now you're at least down to 100 mg TC/week starting dose, which is still inappropriate, but at least not 120 mg?

We could do this AI thing all day.

Query to grok:
It is asserted that doses of testosterone cypionate averaging 100-120 mg per week result in above-physiological levels of serum testosterone in a large majority of men, whether average, peak or both. This is based in part on the normal production range for testosterone in men being about 3-9 mg daily, but generally around 6-7 mg in healthy young men. Apologists for these higher doses claim that serum levels at these doses can be physiological, but they rely on at least three misdirections: Measuring levels at pre-injection troughs, which fails to take into account above-physiological peak and average levels; Not accounting for the existence of lower average levels in healthy young men resulting from a significant diurnal variation in levels; failing to consider free testosterone, which is important at higher doses that tend to drive SHBG down to much lower levels, artificially driving down total testosterone. Evaluate this position.

Grok:
The position is largely accurate and well-supported by pharmacokinetic (PK) data, with important nuances around inter-individual variability and clinical practice. It correctly highlights that 100–120 mg/week testosterone cypionate (TC; 70 mg pure testosterone base delivered, or ~10 mg/day) exceeds endogenous production rates (3–9 mg/day, averaging 5–7 mg/day in young healthy men) and often produces serum levels that exceed a strict physiological profile when considering full exposure (peaks, averages/AUC, and free testosterone). The three “misdirections” are real issues frequently seen in discussions of TRT dosing.

Dose vs. Natural Production and Resulting Serum Levels

Endogenous production is well-established at ~5–7 mg/day pure testosterone. A 100 mg TC injection delivers ~1.5× that weekly mass after accounting for the ester. In hypogonadal men (where exogenous TC fully replaces production):

• Peaks: Frequently supraphysiological. A key review of IM TC/TE regimens shows C_max >1,200 ng/dL (often at 24–48 h post-injection) for 100 mg/week equivalents. Even weekly dosing produces transient peaks of 800–1,200+ ng/dL in many men.
• Averages (C_avg over the dosing interval): Often high-normal to mildly supraphysiological. The same review reports mean C_avg of ~1,055 ng/dL for 100 mg/week TE (very similar PK to TC) and ~943 ng/dL for 200 mg every 2 weeks. Other data (including Wikipedia summaries of dose-response studies) cite ~700 ng/dL average for 100 mg/week TC.
• Troughs (nadir, pre-injection): Typically mid-normal (400–700 ng/dL), e.g., 542 ng/dL nadir in a landmark dose-response study with 125 mg/week TE.

Large fluctuations (peak-to-trough ratios 2–5+) occur with any weekly-or-less-frequent regimen—far greater than natural diurnal variation (peak-to-trough ratio 1.3 in young men). In short, yes: in a substantial proportion of men (high inter-individual variability from clearance, body weight, injection site, etc.), peaks and/or weekly averages exceed the upper normal range (1,000–1,100 ng/dL) or high-normal reference values. Not every man experiences “constantly” supra levels (many titrate successfully to mid-range), but the position’s core assertion holds for a large majority when looking beyond isolated troughs.

Evaluation of the Three “Misdirections”

1. Trough-only measurement: Valid and common critique. Guidelines and reviews explicitly note that troughs can appear “physiological” (e.g., 400–600 ng/dL) while peaks and overall exposure (AUC) are supra. Monitoring is ideally midway between injections or includes peak assessment for fluctuating regimens; symptoms + full profile matter more than a single trough.
2. Ignoring lower 24-hour averages from natural diurnal variation: Correct. Reference ranges (300–1,000+ ng/dL) are based on morning samples, which are 20–35% higher than afternoon levels in young men. True 24-hour integrated exposure in healthy young men is therefore lower than a steady “mid-normal” on TRT. Exogenous TC provides flatter (but often higher total) exposure without the natural rhythm, so a “normal” average on 100–120 mg/week can represent greater overall androgen exposure than endogenous physiology.
3. Failing to account for free testosterone and SHBG suppression: Strong point. Exogenous testosterone suppresses SHBG (dose-dependently, often 10–30% at TRT doses), increasing the free fraction. A “normal” total T with lowered SHBG can equate to elevated free/bioavailable T and greater biological activity. Free T monitoring is clinically relevant at these doses; total T alone underestimates exposure.

Nuances and Clinical Context
Huge variability means some men achieve mid-normal averages (450–700 ng/dL) on 75–100 mg/week with proper titration/frequent dosing (e.g., twice-weekly or daily subcutaneous). Guidelines (Endocrine Society, AUA) explicitly recommend starting at 75–100 mg/week (or 150–200 mg every 2 weeks) and titrating to mid-normal range (target ~400–700 ng/dL, often measured 1 week post-injection or midway) plus symptom relief—not fixed high doses.

The position overstates slightly by implying “large majority… constantly above” without acknowledging that many patients are successfully managed in-range with monitoring and adjustments. However, it accurately critiques overly simplistic claims that these doses are always “physiological” without qualifiers.

Bottom line: The critique is evidence-based and underscores why frequent smaller dosing (or alternatives like gels) better mimics physiology and why monitoring should include timing, free T, and symptoms—not just trough total T. There remains no robust evidence that routinely allowing supraphysiological levels improves overall health outcomes versus careful mid-normal targeting (and higher levels increase risks like erythrocytosis). Individualized care with an experienced clinician is essential.

--------------------------------------------

Put another way:

Query to grok:
Looked at another way, given that the normal range of testosterone production in healthy men is 3-9 mg per day, what fraction of men starting testosterone replacement therapy with doses of 100+ mg/week of testosterone cypionate would be exceeding their healthy natural rate of production?

Grok:
Virtually all men (≥99%) starting testosterone replacement therapy (TRT) with doses of 100+ mg/week testosterone cypionate (TC) will exceed their individual healthy natural rate of testosterone production.

Direct Calculation of Daily Input

• Testosterone cypionate is ~70% testosterone base by molecular weight (standard pharmaceutical fact: 100 mg TC delivers ~70 mg pure testosterone).
• 100 mg TC/week = ~70 mg pure testosterone/week = exactly 10 mg/day average delivered (near-100% bioavailability with intramuscular or subcutaneous injection).
• 120 mg TC/week = ~84 mg pure testosterone/week = 12 mg/day.
• Any dose “100+ mg/week” therefore delivers ≥10 mg pure testosterone per day on average.

Comparison to Natural Endogenous Production

The normal physiological production range in healthy young men is given in the query as 3–9 mg/day (with typical mean/average values consistently reported in the literature as ~5–7 mg/day, often cited as ~6 mg/day). Classic metabolic studies and reviews describe this range (sometimes extended slightly to 3–10 mg/day) as encompassing essentially the full span of healthy adult male production.

On TRT:

• Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal (HPG) axis via negative feedback.
• Endogenous (testicular) testosterone production drops to very low or near-zero levels in the large majority of hypogonadal men within weeks.

Thus, the net daily testosterone input on TRT equals the exogenous dose rate (≥10 mg/day). This exceeds the upper end of the normal healthy range (9 mg/day) for virtually every man.

Fraction Exceeding Personal Healthy Rate

• Each man has his own “healthy natural rate” somewhere within the 3–9 mg/day span.
• A fixed input of ≥10 mg/day exceeds every value ≤9 mg/day.
• Even if we treat 3–9 mg/day as an approximate 95–99% population range (or ±2 SD around a ~6 mg mean, as implied by your earlier point), the tail of men with truly natural production ≥10 mg/day is negligible (<1%).
• Therefore, the fraction exceeding their personal healthy natural rate is ≥99% (essentially 100% when using the 3–9 mg/day range exactly as stated). At doses clearly above 100 mg/week, it is indistinguishable from 100%.

This is a straightforward mass-balance issue independent of serum levels, SHBG, free testosterone, or injection timing. It explains why once-weekly 100–120 mg regimens frequently produce high-normal to supraphysiological average exposure (and elevated free T) in the majority of men, as discussed previously. More physiological replacement (closer to 5–8 mg/day input) is achievable with lower starting doses (e.g., 60–90 mg/week TC) or more frequent/split dosing (twice-weekly or daily subcutaneous), with individualized titration guided by symptoms, labs, and hematocrit.

No large-scale study directly measures production-rate distribution in thousands of men (it requires isotope-dilution techniques), but the cited range and mean values are robust across decades of endocrine literature. This reinforces that standard 100+ mg/week starting doses are, in production-rate terms, supraphysiological for nearly everyone. Individual monitoring and dose adjustment remain essential; there is still no evidence that routinely exceeding natural production rates improves overall health outcomes compared with careful mid-normal targeting. Consult a clinician experienced in PK-guided TRT for personalized dosing.

 

[Phil Goodman]

How sad that you cannot acknowledge basic logic:

There's no evidence that above-range dosing is beneficial to overall health. There is evidence that above-range dosing is harmful to overall health. Dosing with 100 mg TC/week results in above-range levels in most men. Therefore do not start TRT with >= 100 mg TC/week.

So now you're at least down to 100 mg TC/week starting dose, which is still inappropriate, but at least not 120 mg?

We could do this AI thing all day.

Query to grok:
It is asserted that doses of testosterone cypionate averaging 100-120 mg per week result in above-physiological levels of serum testosterone in a large majority of men, whether average, peak or both. This is based in part on the normal production range for testosterone in men being about 3-9 mg daily, but generally around 6-7 mg in healthy young men. Apologists for these higher doses claim that serum levels at these doses can be physiological, but they rely on at least three misdirections: Measuring levels at pre-injection troughs, which fails to take into account above-physiological peak and average levels; Not accounting for the existence of lower average levels in healthy young men resulting from a significant diurnal variation in levels; failing to consider free testosterone, which is important at higher doses that tend to drive SHBG down to much lower levels, artificially driving down total testosterone. Evaluate this position.

Grok:
The position is largely accurate and well-supported by pharmacokinetic (PK) data, with important nuances around inter-individual variability and clinical practice. It correctly highlights that 100–120 mg/week testosterone cypionate (TC; 70 mg pure testosterone base delivered, or ~10 mg/day) exceeds endogenous production rates (3–9 mg/day, averaging 5–7 mg/day in young healthy men) and often produces serum levels that exceed a strict physiological profile when considering full exposure (peaks, averages/AUC, and free testosterone). The three “misdirections” are real issues frequently seen in discussions of TRT dosing.

Dose vs. Natural Production and Resulting Serum Levels

Endogenous production is well-established at ~5–7 mg/day pure testosterone. A 100 mg TC injection delivers ~1.5× that weekly mass after accounting for the ester. In hypogonadal men (where exogenous TC fully replaces production):

• Peaks: Frequently supraphysiological. A key review of IM TC/TE regimens shows C_max >1,200 ng/dL (often at 24–48 h post-injection) for 100 mg/week equivalents. Even weekly dosing produces transient peaks of 800–1,200+ ng/dL in many men.
• Averages (C_avg over the dosing interval): Often high-normal to mildly supraphysiological. The same review reports mean C_avg of ~1,055 ng/dL for 100 mg/week TE (very similar PK to TC) and ~943 ng/dL for 200 mg every 2 weeks. Other data (including Wikipedia summaries of dose-response studies) cite ~700 ng/dL average for 100 mg/week TC.
• Troughs (nadir, pre-injection): Typically mid-normal (400–700 ng/dL), e.g., 542 ng/dL nadir in a landmark dose-response study with 125 mg/week TE.

Large fluctuations (peak-to-trough ratios 2–5+) occur with any weekly-or-less-frequent regimen—far greater than natural diurnal variation (peak-to-trough ratio 1.3 in young men). In short, yes: in a substantial proportion of men (high inter-individual variability from clearance, body weight, injection site, etc.), peaks and/or weekly averages exceed the upper normal range (1,000–1,100 ng/dL) or high-normal reference values. Not every man experiences “constantly” supra levels (many titrate successfully to mid-range), but the position’s core assertion holds for a large majority when looking beyond isolated troughs.

Evaluation of the Three “Misdirections”

1. Trough-only measurement: Valid and common critique. Guidelines and reviews explicitly note that troughs can appear “physiological” (e.g., 400–600 ng/dL) while peaks and overall exposure (AUC) are supra. Monitoring is ideally midway between injections or includes peak assessment for fluctuating regimens; symptoms + full profile matter more than a single trough.
2. Ignoring lower 24-hour averages from natural diurnal variation: Correct. Reference ranges (300–1,000+ ng/dL) are based on morning samples, which are 20–35% higher than afternoon levels in young men. True 24-hour integrated exposure in healthy young men is therefore lower than a steady “mid-normal” on TRT. Exogenous TC provides flatter (but often higher total) exposure without the natural rhythm, so a “normal” average on 100–120 mg/week can represent greater overall androgen exposure than endogenous physiology.
3. Failing to account for free testosterone and SHBG suppression: Strong point. Exogenous testosterone suppresses SHBG (dose-dependently, often 10–30% at TRT doses), increasing the free fraction. A “normal” total T with lowered SHBG can equate to elevated free/bioavailable T and greater biological activity. Free T monitoring is clinically relevant at these doses; total T alone underestimates exposure.

Nuances and Clinical Context
Huge variability means some men achieve mid-normal averages (450–700 ng/dL) on 75–100 mg/week with proper titration/frequent dosing (e.g., twice-weekly or daily subcutaneous). Guidelines (Endocrine Society, AUA) explicitly recommend starting at 75–100 mg/week (or 150–200 mg every 2 weeks) and titrating to mid-normal range (target ~400–700 ng/dL, often measured 1 week post-injection or midway) plus symptom relief—not fixed high doses.

The position overstates slightly by implying “large majority… constantly above” without acknowledging that many patients are successfully managed in-range with monitoring and adjustments. However, it accurately critiques overly simplistic claims that these doses are always “physiological” without qualifiers.

Bottom line: The critique is evidence-based and underscores why frequent smaller dosing (or alternatives like gels) better mimics physiology and why monitoring should include timing, free T, and symptoms—not just trough total T. There remains no robust evidence that routinely allowing supraphysiological levels improves overall health outcomes versus careful mid-normal targeting (and higher levels increase risks like erythrocytosis). Individualized care with an experienced clinician is essential.

--------------------------------------------

Put another way:

Query to grok:
Looked at another way, given that the normal range of testosterone production in healthy men is 3-9 mg per day, what fraction of men starting testosterone replacement therapy with doses of 100+ mg/week of testosterone cypionate would be exceeding their healthy natural rate of production?

Grok:
Virtually all men (≥99%) starting testosterone replacement therapy (TRT) with doses of 100+ mg/week testosterone cypionate (TC) will exceed their individual healthy natural rate of testosterone production.

Direct Calculation of Daily Input

• Testosterone cypionate is ~70% testosterone base by molecular weight (standard pharmaceutical fact: 100 mg TC delivers ~70 mg pure testosterone).
• 100 mg TC/week = ~70 mg pure testosterone/week = exactly 10 mg/day average delivered (near-100% bioavailability with intramuscular or subcutaneous injection).
• 120 mg TC/week = ~84 mg pure testosterone/week = 12 mg/day.
• Any dose “100+ mg/week” therefore delivers ≥10 mg pure testosterone per day on average.

Comparison to Natural Endogenous Production

The normal physiological production range in healthy young men is given in the query as 3–9 mg/day (with typical mean/average values consistently reported in the literature as ~5–7 mg/day, often cited as ~6 mg/day). Classic metabolic studies and reviews describe this range (sometimes extended slightly to 3–10 mg/day) as encompassing essentially the full span of healthy adult male production.

On TRT:

• Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal (HPG) axis via negative feedback.
• Endogenous (testicular) testosterone production drops to very low or near-zero levels in the large majority of hypogonadal men within weeks.

Thus, the net daily testosterone input on TRT equals the exogenous dose rate (≥10 mg/day). This exceeds the upper end of the normal healthy range (9 mg/day) for virtually every man.

Fraction Exceeding Personal Healthy Rate

• Each man has his own “healthy natural rate” somewhere within the 3–9 mg/day span.
• A fixed input of ≥10 mg/day exceeds every value ≤9 mg/day.
• Even if we treat 3–9 mg/day as an approximate 95–99% population range (or ±2 SD around a ~6 mg mean, as implied by your earlier point), the tail of men with truly natural production ≥10 mg/day is negligible (<1%).
• Therefore, the fraction exceeding their personal healthy natural rate is ≥99% (essentially 100% when using the 3–9 mg/day range exactly as stated). At doses clearly above 100 mg/week, it is indistinguishable from 100%.

This is a straightforward mass-balance issue independent of serum levels, SHBG, free testosterone, or injection timing. It explains why once-weekly 100–120 mg regimens frequently produce high-normal to supraphysiological average exposure (and elevated free T) in the majority of men, as discussed previously. More physiological replacement (closer to 5–8 mg/day input) is achievable with lower starting doses (e.g., 60–90 mg/week TC) or more frequent/split dosing (twice-weekly or daily subcutaneous), with individualized titration guided by symptoms, labs, and hematocrit.

No large-scale study directly measures production-rate distribution in thousands of men (it requires isotope-dilution techniques), but the cited range and mean values are robust across decades of endocrine literature. This reinforces that standard 100+ mg/week starting doses are, in production-rate terms, supraphysiological for nearly everyone. Individual monitoring and dose adjustment remain essential; there is still no evidence that routinely exceeding natural production rates improves overall health outcomes compared with careful mid-normal targeting. Consult a clinician experienced in PK-guided TRT for personalized dosing.

How sad is it that I’ve shoved your face in multiple studies which showed just that(above range dosing provided more benefits for muscle gain, fat loss, bone density improvements, metabolic improvements, and lots of other benefits)… yet you continue to lie and say they don’t exist.



And yes, we could do the AI thing all day long. I can just as easily lead it to support my case over yours.



Prompt:

It is asserted that doses of testosterone cypionate 50 mg per week result in levels of serum testosterone sufficient for symptom resolution and maximized benefits in a large majority of men. This is based in part on the normal production range for testosterone in men being about 3-9 mg daily, but generally around 6-7 mg in healthy young men. Supporters of these smaller doses claim that serum levels at these doses are just as good or better than the more commonly seen doses of 75-100 mg per week, but they rely on at least three misdirections: Binding an unnatural process to natural restrictions, which fails to take into account there will always be differences in peaks and troughs due to the half-life of injectable testosterone compared to natural pulsations. Oversimplifying language in guidance which states “to minimize supraphysiological levels”. To sufficiently hit levels needed for symptom resolution patients generally need to spend at least some time at supraphysiological levels, hence why they say to minimize the time and not “avoid at all costs”. Completely ignoring studies which show that patients at doses ranging from 100-125 saw the most benefits as well as minimal risks, and also ignoring the countless studies which show blood levels seen from 50 mg are often too low for most patients. They also completely ignore recommended guidelines which support 75-100 mg as a standard starting dose. Evaluate this position.





The assertion—that 50 mg/week of testosterone cypionate (TC) produces serum levels sufficient for symptom resolution and maximized benefits in a “large majority” of hypogonadal men, based on natural daily production rates (3–9 mg/day, averaging 6–7 mg in young healthy men)—is overstated and incomplete. It overlooks key pharmacokinetic differences, clinical trial data on dose-response relationships, real-world serum level outcomes, and major society guidelines. The three “misdirections” identified in the query accurately describe common flaws in arguments favoring this low-dose approach. Below is a structured evaluation grounded in established evidence.


Natural Production Equivalence Is Misleading (First Misdirection)


Natural testicular production of pure testosterone is indeed ~3–10 mg/day (typically 6–7 mg in young men). A 50 mg weekly TC injection superficially matches this on a mass basis. However, TC is an ester (~67–70% testosterone by weight after cleavage), so it delivers roughly 33–35 mg of actual testosterone per week (~4.7–5 mg/day equivalent). More importantly, exogenous injection does not replicate natural physiology:


• Natural secretion follows a diurnal rhythm with modest fluctuations.


• TC (half-life ~8 days) produces noticeable peaks (often 1–3 days post-injection) and troughs (day 7), even with weekly dosing.


This leads to inconsistent exposure compared to endogenous production. In hypogonadal men (who already have impaired feedback/SHBG dynamics), 50 mg/week frequently yields borderline or subtherapeutic levels rather than reliably matching “natural” serum concentrations. Studies of subcutaneous (SC) or intramuscular (IM) dosing at 50 mg/week show average total testosterone around 400–600 ng/dL in some cohorts, but with troughs often in the lower half of normal (or below 300 ng/dL in individuals). One analysis of SC testosterone (doses 50–100 mg/week, median 75 mg) found that all patients with levels confined to the lower half of the normal range were on exactly 50 mg/week; one such patient dipped below normal at trough. This is not “just as good” as higher dosing for consistent therapeutic exposure.


“Minimize Supraphysiological Levels” Guidance Is Oversimplified (Second Misdirection)


Guidelines (e.g., Endocrine Society 2018) recommend targeting mid-normal serum testosterone (roughly 400–700 ng/dL, or specifically 400–700 ng/dL at 1 week post-IM injection) to balance benefits and risks. They explicitly say “minimize” (or aim to keep within physiologic range), not “avoid at all costs.” For weekly IM/SC regimens, modest peaks above the upper normal limit are inherent due to pharmacokinetics but are far smaller and shorter-lived than with traditional 200 mg every 2 weeks. Symptom relief and physiologic effects (e.g., erythropoiesis, muscle maintenance) often require spending some time in the upper-normal or briefly supraphysiologic range; strict avoidance can leave patients under-treated. The low-dose argument sometimes treats any excursion above normal as inherently bad, ignoring that guidelines prioritize symptom response and mid-range trough/average levels over rigid avoidance.


Evidence on Serum Levels, Benefits, and Guidelines Is Selectively Ignored (Third Misdirection)


Multiple lines of evidence contradict the claim that 50 mg/week is optimal or sufficient for most men:


• Serum levels from 50 mg/week are often inadequate. Pharmacokinetic studies and clinical series (including SC TC/TE analogs) show troughs frequently ~300–400 ng/dL or lower-half normal. One patient-level analysis explicitly noted subnormal readings at 50 mg. In contrast, 75–100 mg/week more reliably sustains mid-normal averages (e.g., ~500–700 ng/dL).


• Dose-response studies demonstrate greater benefits at 100–125 mg/week equivalents. The landmark Bhasin et al. (2001) trial (GnRH agonist suppression of endogenous production + weekly testosterone enanthate in young men) is particularly relevant. Nadir (trough) serum levels were:


• 50 mg/week → 306 ng/dL


• 125 mg/week → 542 ng/dL
Fat-free mass increased dose-dependently and significantly only at 125 mg (+3.4 kg) and higher; changes correlated strongly with testosterone concentration (r = 0.73). Leg press strength, muscle volume, hemoglobin, and IGF-I also rose in a dose-dependent manner. Sexual function did not differ across doses, but anabolic/strength benefits clearly favored 125 mg over 50 mg. Similar patterns appear in follow-up work on older men. These findings align with the query’s point: 100–125 mg/week often yields the best combination of benefits (muscle, strength, energy, libido) with manageable risks when monitored.


• Guidelines explicitly support higher starting doses.


• Endocrine Society (2018): Suggests 75–100 mg IM TC weekly (or 150–200 mg every 2 weeks) as a standard regimen; aim for mid-normal levels. FDA labeling allows 50–400 mg every 2–4 weeks but is outdated for modern weekly practice.


• AUA (2018/updated): Prefers smaller, more frequent doses (e.g., starting 100 mg weekly) over large infrequent ones to limit time outside normal range; target middle tertile (~450–600 ng/dL).


Real-world TRT practice reflects this: most men start at 100–200 mg/week total (often split), with titration based on symptoms and labs. 50 mg/week is sometimes used for micro-dosing in very mild cases or to minimize side effects (e.g., hematocrit rise, estradiol), but it is not the default or sufficient for symptom maximization in a “large majority.”


Overall Assessment and Practical Implications


The low-dose assertion has a kernel of truth—some men (especially those with low SHBG, high sensitivity, or very mild hypogonadism) achieve adequate symptom relief and normal-range levels on 50 mg/week with fewer side effects. However, it does not hold for the majority when “maximized benefits” and consistent therapeutic levels are the goal. Pharmacokinetic mismatch, dose-response data (e.g., Bhasin), and guideline consensus all favor starting at 75–100 mg/week (or equivalent split dosing) and titrating to symptoms/labs rather than defaulting to 50 mg based on a simplistic production-rate analogy.


Risks (e.g., erythrocytosis, estradiol elevation) are dose-related but manageable with monitoring and adjustment; recent large trials confirm cardiovascular safety of properly dosed TRT. Therapy must remain individualized—measure trough or mid-cycle levels, assess symptoms, and adjust. Blanket claims that 50 mg is “just as good or better” ignore the evidence base and can lead to under-treatment. Patients should discuss with a knowledgeable clinician rather than relying on production-rate equivalency alone.

 

[Phil Goodman]

@Cataceous I guess at least the one thing you have going for you is that your cognitive dissonance is so strong you’re not even embarrassed by how deep the hole is that you’ve dug.


I’ve provided studies which show doses of 100 mg are superior to 50

I’ve shared studies which show that the blood levels on 50 mg/week can often be too low for full maximization of benefits.

I’ve shared studies which showed that doses of 100 mg can keep people within a good range


I’ve provided many studies which showed those doses(100-120) are safe and well-tolerated in most patients

I’ve provided guidelines from multiple health organizations that list 75-100 mg/week as a traditional starting dose.

I’ve shown that the foundation of your entire argument(minizming time outside of physiological levels… which you interpret from a hardliners stance of “AVOID AT ALL COSTS!!!”) is listed in the lowest priority category and also as having the weakest classification of support evidence. Again, it’s on par with their recommendation and evidence for prescribing AIs.

And then you take it even further by acting like comparing natural production to injectable test is an apples to apples comparison and that any time spent above a normal level is instantly and automatically bad. Lastly, you continue to lie and say all of the points I highlighted above don’t exist.



But again, at this point I’m just wasting my time trying to teach a dog algebra. I tried to find a common ground after growing tired of your constant bobbing and weaving and cognitive dissonance(not to mention the lies about which studies do or don’t exist and the guidelines from various medical associations). Yet you refused and just continue to double down, resulting to framing the opposing view in the worst possible way in vague terms so that a LLM could tell you there’s no evidence that running levels over 1,500 is better than running levels around 600 or so… and acting like that was a huge victory. That is honestly what you’ve resorted to here due to your cognitive dissonance. So again I would recommend going back and watching the video if you haven’t already done so. Otherwise I’m done in this thread and won’t be back until you feel the need to move my posts here after lying to someone else on the forum and saying there is no evidence for my claim that 100 mg/week is a good starting dose.