Guidelines tell you how to start therapy. They say much less about month seven, when the patient emails to say it stopped working, or month three, when his partner is asking about the acne. This Part is the troubleshooting manual.
'It Stopped Working'
- 1Confirm the level was drawn at the correct time for the formulation
- 2Confirm adherence and technique — missed doses, gel washed off, wrong injection site
- 3Is the level actually at target (roughly 400–700 ng/dL)?
- 4If yes: reopen the differential — OSA, depression, thyroid, anemia, medications, relationship and situational factors
- 5If no: adjust interval before dose; verify the product and pharmacy
- 6Reassess the specific symptom that was targeted, not a global sense of wellness
In practice, the most common reason a man at a therapeutic testosterone level still feels poorly is that testosterone deficiency was not the primary driver of his symptoms. Untreated sleep apnea and untreated depression are the two leading culprits. Escalating the dose in this situation produces adverse effects without benefit.
Adverse Effect Playbook
| Problem | Likely mechanism | First-line management |
|---|---|---|
| Erythrocytosis | Androgen-driven erythropoiesis; peak-concentration dependent | See Part V thresholds. Shorten interval, reduce dose, treat OSA, consider transdermal switch, phlebotomy if needed. |
| Acne, oily skin | Androgen effect on sebaceous glands; often peak-related | Usually improves after the first few months. Topical retinoid or benzoyl peroxide; reduce peak by shortening the dosing interval; dermatology if severe or scarring. |
| Gynecomastia or breast tenderness | Aromatization to estradiol, often peak-driven | Reduce peaks by shortening interval or lowering dose. Measure estradiol with a sensitive assay only if it will change management. Examine for asymmetry or a discrete mass, which requires imaging. |
| Testicular atrophy | LH suppression reduces Leydig cell stimulation; expected pharmacology | Counsel that this is expected and usually partly reversible on discontinuation. hCG can maintain testicular volume, but should be framed as fertility-directed and off-label for this indication. |
| Fluid retention, ankle edema | Sodium and water retention; more prominent in heart failure and CKD | Reduce dose. Reassess cardiac and renal status. Avoid or discontinue in decompensated heart failure. |
| Mood lability, irritability | Often peak-related in men on long-interval injections | Shorten the interval. Screen for underlying mood disorder. Supraphysiologic levels should be corrected downward. |
| Worsening sleep apnea or new snoring | Testosterone can worsen OSA in susceptible men | Sleep study. Treat OSA. Reduce dose or hold pending evaluation if severe. |
| Male pattern hair loss | DHT effect in genetically susceptible men | Counsel before starting. Topical minoxidil; finasteride is an option but discuss its effects on sexual function and PSA interpretation. |
| Injection-site pain, nodules | Oil vehicle, needle gauge, technique, IM depth | Switch to subcutaneous with a smaller-gauge needle, rotate sites, warm the vial, inject slowly. |
| Skin reaction to gel or patch | Vehicle irritation, alcohol content | Rotate sites, try a different vehicle or brand, switch to injectable. |
| Elevated blood pressure | Class effect noted for oral undecanoate and SC enanthate auto-injector | Monitor at every visit. Treat hypertension. Reconsider the formulation if the rise is attributable to it. |
Most testosterone adverse effects are peak-concentration problems disguised as dose problems. Before you reduce the total weekly dose and lose efficacy, try delivering the same dose more often.
The Patient Buying Testosterone Online
You will encounter men using testosterone or anabolic agents obtained from online vendors, peptide sellers, or a gym. Reflexive moralizing ends the conversation and the patient continues without any medical oversight. A more productive approach is to acknowledge the goal, establish what is actually being taken and at what dose, obtain baseline safety labs including hematocrit, lipids, liver enzymes, and PSA where appropriate, and explain the specific risks that apply — erythrocytosis, hypertension, cardiomyopathy at supraphysiologic doses, infertility, and the fact that product contents are unverified.
- Ask what, how much, from where, and for how long — without judgment.
- Check hematocrit, lipids, comprehensive metabolic panel, PSA where age-appropriate, and blood pressure.
- Discuss infertility explicitly, and offer semen analysis and referral if fertility matters to him.
- Discuss what a supervised, physiologic regimen would look like if he meets criteria.
- Document the discussion, the risks disclosed, and the plan.
- Recognize anabolic steroid use disorder and refer when body-image pathology or dependence is present.
At target and still tired
A 45-year-old man has been on testosterone enanthate 80 mg SC weekly for six months. His trough total testosterone is 585 ng/dL and hematocrit is 47 percent. He reports that libido and morning erections improved substantially in the first two months, but his fatigue and low mood are unchanged. He asks for a dose increase, saying he read online that he needs to be 'over 900.'
How do you respond?