One study answers the "is more better?" question more cleanly than anything else in the literature. Sixty-one healthy young men, aged 18–35, had their own testosterone production suppressed with a GnRH agonist, then received weekly injections of 25, 50, 125, 300 or 600 mg of testosterone enanthate for 20 weeks, with energy and protein intake standardised.[1]
Mean nadir concentrations: 253, 306, 542, 1,345 and 2,370 ng/dL.[1] The top two groups were well above the physiological range.
What rose, what fell, what did not move
| Measure | Result |
|---|---|
| Fat-free mass | ↑ dose-dependently: +3.4, +5.2, +7.9 kg at 125, 300, 600 mg |
| Leg press strength, leg power, thigh and quadriceps volume | ↑ positively correlated with concentration |
| Hemoglobin | ↑ positively correlated |
| IGF-I | ↑ positively correlated |
| Fat mass | ↓ negatively correlated |
| HDL cholesterol | ↓ negatively correlated |
| Sexual function | no significant change at any dose |
| Visual-spatial cognition and mood | no significant change at any dose |
| PSA | no significant change at any dose |
All from the same study.[1] The authors' conclusion: the changes conform to a single linear dose-response relationship, but different androgen-dependent processes have different testosterone dose-response relationships.[1]
The two rows that are the safety story
Hemoglobin rising with dose. Erythrocytosis is already the most common side effect of testosterone therapy, with published guidance to decrease or discontinue above a hematocrit of 54%.[2] A dose-dependent rise means the risk being monitored scales with the number being chased.
HDL cholesterol falling with dose.[1] Not a parameter most men on treatment are watching, and it moves the wrong way.
The limits of this study
Twenty weeks. Long-term consequences of supraphysiological concentrations are not what it measured.
Healthy young men, not hypogonadal patients. Their sexual function and mood were already normal, leaving little room to improve — an important caveat on the null results.
Their own production was suppressed. A clean experimental design, and not a model of ordinary treatment.
What it establishes robustly is the shape: muscle and risk markers scale with concentration; several outcomes do not.
Why the guideline targets mid-normal
Read against this data, mid-normal[3] is not caution for its own sake — it is where the measured trade-off sits best. Above it, two risk markers worsen and the benefits men want do not improve.
Frequently asked questions
Does more testosterone build more muscle? Fat-free mass increased dose-dependently in this study.[1] Treatment for hypogonadism and maximising body composition are different goals with different risk calculus.
Will a higher level make me feel better? Not on this evidence — mood and sexual function showed no significant change at any dose.[1]
Is 2,370 ng/dL dangerous? It is far above physiological. The measured consequences at high concentrations were rising hemoglobin and falling HDL.[1]
What should I aim for? Mid-normal, per the guideline.[3] See what higher doses buy you.
Next in this series
If dose is settled, the remaining question is frequency.
Continue with why your weekly shot makes you feel worse.
References
3 sources
- Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281(6):E1172–E1181. doi:10.1152/ajpendo.2001.281.6.E1172 · PMID 11701431
- Agrawal P, Singh SM, Kohn T. Management of Erythrocytosis in Men Receiving Testosterone Therapy: Clinical Consultation Guide. Eur Urol Focus. 2023;9(1):20–21. doi:10.1016/j.euf.2022.10.008 · PMID 36335038
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
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