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.