Competent testosterone therapy is a short, dull checklist executed properly. There is no optimisation protocol underneath it and no advanced version. The whole of it comes from one guideline.[1]
The checklist
1. Diagnosis on two fasting morning draws, with symptoms. Only in men with symptoms and signs consistent with deficiency and unequivocally, consistently low concentrations — confirmed by repeating the measurement.[1]
2. Free testosterone where indicated. When total is near the lower limit of normal or a condition alters SHBG.[1]
3. A cause investigation. Additional diagnostic evaluation to ascertain the cause of the deficiency.[1] See the functional hypogonadism question.
4. Contraindication screening. Fertility plans in the near term, breast or prostate cancer, palpable prostate nodule, PSA above 4 ng/mL (or above 3 in higher-risk men without urological evaluation), elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within six months, thrombophilia.[1]
5. A mid-normal target. Chosen with patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden and cost in mind.[1]
6. First-year monitoring. Symptoms, adverse effects, compliance, serum testosterone, hematocrit, prostate cancer risk.[1]
That is the standard of care. Six items.
What good treatment also does: set expectations honestly
This is the part no checklist captures, and it is where most dissatisfaction originates. A man told what the trials found will not conclude his treatment failed when it performs exactly as predicted.
Erectile function. TRAVERSE found testosterone improved sexual activity, hypogonadal symptoms and sexual desire — but not erectile function.[2]
Cognition. The T-Trials found no improvement in older men with low testosterone and age-associated memory impairment.[3]
Mood. Real, replicated, explicitly small.[4]
Timing. Sexual interest at ~3 weeks, plateauing at 6. Body composition at 12–16 weeks. Bone still changing at 3 years.[5] See how long TRT takes to work.
What good treatment is not
Not maximisation. Mid-normal is the target.[1] Higher raises hemoglobin and lowers HDL without improving mood or sexual function.[7]
Not a wellness protocol. The indication is confirmed hypogonadism.
Not permanent by default. Compliance, symptoms and adverse effects are reviewed, and treatment can be reconsidered.
Not cardioprotective. TRAVERSE found non-inferiority to placebo, not benefit.[8]
Frequently asked questions
How do I know my provider is doing this properly? Ask two questions: will you confirm the diagnosis on a second fasting morning draw, and what is the first-year monitoring schedule? See online or in-person TRT.
My level is mid-range but I still feel flat. What now? Being at target rules out under-dosing, which redirects the review toward other causes — sleep, thyroid, mood, medication.
Is there a more advanced protocol? No. The guideline is the standard.[1]
Next in this series
Where all of this stands now, after the trials that finally answered the big questions.
Continue with the state of TRT.
References
8 sources
- 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
- Pencina KM, Travison TG, Cunningham GR, et al. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. J Clin Endocrinol Metab. 2024;109(2):569–580. doi:10.1210/clinem/dgad484 · PMID 37589949
- Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017;317(7):717–727. doi:10.1001/jama.2016.21044 · PMID 28241356
- Bhasin S, Seidman S, Travison TG, et al. Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy. J Clin Endocrinol Metab. 2024;109(7):1814–1826. doi:10.1210/clinem/dgae026 · PMID 38205962
- Saad F, Aversa A, Isidori AM, et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011;165(5):675–685. doi:10.1530/EJE-11-0221 · PMID 21753068
- Grabner M, Hepp Z, Raval A, et al. Topical Testosterone Therapy Adherence and Outcomes Among Men With Primary or Secondary Hypogonadism. J Sex Med. 2018;15(2):148–158. doi:10.1016/j.jsxm.2017.11.225 · PMID 29425664
- 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
- Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322