TRT after 40 — the decision framework after the 2024 reanalysis.

TRAVERSE 2023 settled the cardiovascular question. Most prescribers haven't caught up. Here's the framework: who benefits, who shouldn't touch it, what the bloodwork actually means.

Testosterone replacement therapy has been the most argued-about medical decision in men's health for fifteen years. The 2024 TRAVERSE trial, published in NEJM, finally gave us the cardiovascular safety data the field had been waiting for. It changed the conversation. Most prescribers haven't caught up.

This piece is the decision framework: who benefits, who shouldn't touch it, what the bloodwork actually means, the difference between TRT and a peptide stack, and what to ask for if you're going to have the conversation.

What changed in 2024

For two decades, the field operated under the cardiovascular shadow of two flawed observational studies (Vigen 2013, Finkle 2014) that suggested TRT might raise heart-attack risk. Both had serious design problems. They scared a generation of doctors away from prescribing.

TRAVERSE (Lincoff et al, NEJM 2023) was the prospective, randomized, placebo-controlled trial designed to settle the question. 5,246 men aged 45-80 with low T and existing or high CV risk, followed an average of 33 months. Result: testosterone replacement to a normal range did not increase major adverse cardiovascular events.

It did slightly increase atrial fibrillation, pulmonary embolism, and acute kidney injury — real signals worth discussing — but the cardiovascular bogeyman that kept TRT off the menu for a generation was, on the best available evidence, not real.

Who actually benefits

The Endocrine Society 2018 guideline (Bhasin et al) is the framework. Symptomatic hypogonadism = unequivocally low testosterone plus consistent symptoms. Both halves matter.

Low T alone, asymptomatic: Not a TRT indication. Probably not a problem worth chasing.

Symptoms alone, normal T: Not a TRT indication. Look for the actual cause — sleep apnea, depression, obesity, thyroid, alcohol use, medication side effects. About 60% of "low T" complaints in primary care are actually one of those.

Both: The legitimate population. About 2-6% of men in their 40s, rising to about 20% in their 70s.

The bloodwork that actually matters

Get these, between 7-10 AM, fasted, repeated on two separate mornings if any are low or borderline:

• Total testosterone — the headline number. Below 264 ng/dL (Endocrine Society cutoff) on two morning samples = unequivocally low
• Free testosterone — what's actually available to your tissues. SHBG-corrected if measured directly
• SHBG — sex hormone binding globulin. High SHBG means most of your "total" T is unavailable
• LH and FSH — distinguishes primary (testicular) from secondary (pituitary) hypogonadism, which matters for treatment choice
• Estradiol (E2, sensitive assay) — too high or too low both cause symptoms
• Prolactin — elevation can suppress T and indicates pituitary issue
• PSA — baseline before any treatment
• Hematocrit — TRT raises it; baseline matters for monitoring

TRT vs peptides — what they actually do

These get conflated constantly. They are not the same.

TRT = exogenous testosterone. Either injection (cypionate or enanthate, IM or subQ), gel, pellet, or oral (newer formulations). It replaces your testosterone with manufactured testosterone. It works. It will also shut down your natural production within weeks. Reversible for most men, but you're on it until you decide not to be.

Peptides (the legitimate medical ones — sermorelin, ipamorelin, CJC-1295) act on the pituitary to stimulate your own growth hormone pulse. Some peptides (BPC-157, TB-500) target tissue healing and are unrelated to the HPG axis. None of them meaningfully raise testosterone in symptomatic-hypogonadal men. They do other things. The bro-internet conflation of TRT and peptides is a categorical error.

If you have actual symptomatic low T, peptides will not fix it. If you have soft-tissue injuries, gut issues, or want a recovery support — peptides may be useful (see our peptides letter). Different problems, different tools.

How to have the conversation

If your testosterone is low and symptoms are real, the right conversation is with a clinician who actually treats hypogonadism (urologist, endocrinologist, or a TRT-focused telehealth practice). Not your GP who saw it in a 1-hour CME slide in 2018.

Ask for:

1. The full panel above, not just total T
2. A clear discussion of treatment options (injection vs gel vs pellet — they're not equivalent)
3. The monitoring plan — hematocrit, PSA, E2, symptom check at 3 and 6 months
4. The exit plan if you decide to come off

What this isn't

TRT is not a performance enhancer for normal-T men. The athletes-and-influencers using it as a vanity drug are doing supraphysiologic dosing in a different category. It is also not a permanent fix for problems that aren't actually hypogonadal — depression with normal T won't respond to TRT, weight loss with normal T won't accelerate with TRT, low libido with normal T usually has a relational or psychological driver.

What it is: a real medical treatment for a real medical condition that the cardiovascular panic of 2013-2014 kept under-prescribed for a decade. The 2024 reanalysis changed the math. The conversation should change with it.