Monitoring is where testosterone therapy is either safe or not. The good news is that the required monitoring is short, cheap, and well defined. The failure mode in practice is not that the monitoring is difficult — it is that it silently stops happening after the first year.
The Monitoring Calendar
| Timepoint | Testosterone level | Hematocrit / Hgb | PSA | Other |
|---|---|---|---|---|
| Baseline | Two confirmatory morning values | Yes | Yes if age ≥40 or risk factors | LH, FSH, SHBG, prolactin as indicated; DRE; blood pressure |
| 3 months | Yes, timed to formulation | Yes | Yes if age ≥40 or risk factors | Symptom reassessment; adherence; injection technique; blood pressure |
| 6 months | Yes if dose changed | Yes | Yes if age ≥40 or risk factors | Symptom reassessment |
| 12 months | Yes | Yes | Yes if age ≥40 or risk factors | Full reassessment; reconfirm ongoing benefit |
| Annually thereafter | Yes | Yes | Per shared decision and age | Blood pressure, symptoms, adverse effects, continued indication |
Erythrocytosis
Testosterone stimulates erythropoiesis, partly through suppression of hepcidin and increased iron availability. Erythrocytosis is the most common adverse effect requiring intervention, is more frequent with injectable formulations and with higher peak concentrations, and is more likely in men who smoke, who have obstructive sleep apnea, or who have chronic lung disease.
| Hematocrit | Action |
|---|---|
| Below 50% | Continue current therapy; routine monitoring |
| 50–53% | Recheck; address contributors — smoking, untreated OSA, dehydration at draw. Consider reducing dose or shortening the interval to lower peaks. |
| 54% or above | Hold or reduce therapy. Evaluate for OSA and other causes. Consider switching from injectable to transdermal. Therapeutic phlebotomy may be used, with hematology input for recurrent cases. Do not simply continue at the same dose. |
A rising hematocrit on therapy should prompt a look at smoking status, sleep apnea, altitude, chronic hypoxemia, and the timing of the draw relative to the injection. Peak-timed draws in a man on every-2-week injections overstate his average exposure. Fix the schedule and the contributors before abandoning an otherwise effective therapy.
Prostate Considerations
Testosterone therapy produces a modest PSA rise in the first several months as the prostate responds to restored androgen exposure, typically stabilizing thereafter. The contemporary evidence, including the prostate safety data collected within TRAVERSE, does not support the historical claim that testosterone therapy causes prostate cancer. It remains contraindicated in active untreated prostate cancer, and men on therapy should receive age-appropriate prostate cancer screening discussions like any other man.
- Obtain a baseline PSA and prostate examination in men aged 40 and older, or younger with risk factors, before initiating.
- Refer to urology for a confirmed PSA increase greater than roughly 1.4 ng/mL within any 12-month period on therapy.
- Refer for a new palpable nodule or induration on examination.
- Refer for a PSA above the age-appropriate threshold, or for symptoms of significant lower urinary tract obstruction.
Prostate safety data from TRAVERSE and multiple meta-analyses are reassuring for men without known prostate cancer; long-term data in men with treated prostate cancer remain limited and specialist-directed.
Estradiol: When It Matters
Testosterone aromatizes to estradiol, and estradiol has genuine physiologic roles in men — bone density, libido, and lipid handling among them. Routine estradiol measurement in an asymptomatic man on stable therapy is not recommended and frequently leads to inappropriate treatment. Measure estradiol when there is a clinical reason: new or worsening gynecomastia, breast tenderness, notable fluid retention, or persistent mood symptoms in a man whose testosterone is at target. When measurement is warranted, a sensitive assay such as LC-MS/MS is preferred, since standard immunoassays perform poorly at male concentrations.
Routine addition of anastrozole to testosterone therapy to 'control estrogen' is not evidence-based, is off-label, and risks driving estradiol too low — with consequences for bone density, libido, and lipids. Reserve aromatase inhibition for symptomatic, confirmed elevation that has not responded to dose reduction or interval adjustment, and consider specialist input.
Routine aromatase inhibitor use in men on testosterone therapy lacks supportive outcome trials; harms from over-suppression of estradiol are mechanistically well established.
What Does Not Need Routine Monitoring
- Liver function tests — modern formulations are not hepatotoxic; this was a concern with 17-alpha-alkylated oral androgens such as methyltestosterone, which are not used for replacement.
- Routine lipid panels beyond standard cardiovascular risk screening.
- Routine estradiol in the asymptomatic patient.
- Routine LH and FSH after therapy has started — they will be suppressed, and that is expected.
The PSA that needed a phone call
A 62-year-old man has been on testosterone gel for 14 months with good symptom response. His baseline PSA was 1.1 ng/mL. At 12 months it was 1.5 ng/mL. He returns at 14 months for an unrelated visit and a repeat PSA is 3.1 ng/mL. Digital rectal examination is normal. He has no urinary symptoms.
What is your interpretation and next step?