The headline: TRT, monitored, is safe
The 2023 TRAVERSE trial — the largest cardiovascular safety trial of testosterone therapy ever conducted (n=5,246, men with hypogonadism + cardiovascular risk factors) — found that testosterone replacement was non-inferior to placebo for major adverse cardiac events over a mean 33 months of follow-up.
That's the most rigorous answer to the "is it safe?" question we've ever had. The answer is: yes, with monitoring.
The job isn't to debate safety — it's to do the monitoring. Three numbers do most of the work.
Number one: Hematocrit
Testosterone increases red blood cell production. For most men this is a feature — slightly higher hematocrit, better oxygen carrying capacity, slightly improved aerobic performance. For some men it goes too far.
The threshold: we get nervous above 52%. We escalate above 54%. Above that, blood viscosity climbs and so does cardiovascular risk.
What we do about it:
- Lower dose first — often solves it
- Switch from IM to SubQ injection — typically reduces hematocrit creep
- Periodic blood donation (therapeutic phlebotomy) — covers stubborn cases
- Increase frequency, decrease per-dose amount — flatter curve
Hematocrit is checked at every Dominant draw — week 0, 8, 16, 24, then quarterly.
Number two: Blood pressure
TRT can raise BP a few mmHg in some men. The effect is modest in most, meaningful in a minority. The mechanism is partly fluid retention, partly hematocrit, partly something else we don't fully understand.
The threshold: we want systolic under 130, diastolic under 85. We act on sustained readings above those.
If your BP rises on TRT, the order is: lower dose, manage hematocrit, address sleep apnea (often the unspoken driver), then add a thiazide or ARB if needed. Most men don't need any of step 4.
Number three: PSA
This is the one most men worry about, and the one with the most reassuring data.
The old fear: testosterone causes prostate cancer. That fear comes from a 1941 paper based on three patients. It survived 70 years of contradictory evidence because it was politically convenient.
The current consensus: testosterone does not cause prostate cancer. What it can do is accelerate the growth of an already-existing cancer. So we screen at baseline, screen quarterly, and act on rising PSA — not on absolute number.
| PSA pattern | What it means | What we do |
|---|---|---|
| Stable, in range | Normal | Continue, re-check quarterly |
| Rising >1.4 ng/mL/yr | Concerning velocity | Hold protocol, urology referral |
| Absolute >4 ng/mL | Above threshold | Hold, refer for evaluation |
The other things we watch
- Estradiol (E2) — too high causes mood changes, water retention, gyno; too low causes joint pain, libido drop, mood floor. Optimal: 20–35 pg/mL.
- Lipids — TRT mildly improves them in most men; we check annually.
- Liver enzymes — modern delivery routes don't stress the liver; we check annually anyway.
- Thyroid — not affected by TRT, but a common confounder for "low T symptoms." We screen at baseline.
- Sleep — sleep apnea is underdiagnosed and amplifies every TRT side effect. We screen with questionnaires; we refer if positive.
The risks of unmonitored TRT are real. The risks of monitored TRT are small. The risks of leaving low T untreated — sarcopenia, depression, metabolic syndrome — are larger than either.— Endocrine Society guidance, paraphrased
What our monitoring schedule actually looks like
| When | What we draw |
|---|---|
| Week 0 | Full panel: T (total/free), SHBG, E2, LH, FSH, prolactin, CBC, CMP, PSA, lipids |
| Week 8 | T, E2, hematocrit |
| Week 16 | Full panel |
| Week 24 | T, E2, hematocrit, BP check |
| Quarterly thereafter | T, E2, hematocrit, PSA, BP |
| Annually | Full panel + lipids + CMP |
This is included in your protocol. Not an add-on. Not a separate bill. The medicine and the instrument are the same product.