Testosterone: who actually needs TRT and what the data show

A group in Sydney ran the study that frames this whole discussion. They recruited 45 men over 40 who had the classic complaints blamed on low testosterone, tiredness, low sex drive, low mood and flat affect, but no disease causing it. Everyone got a testosterone gel for six weeks and a placebo gel for six weeks, with neither the men nor the researchers knowing which was which. Testosterone did its job on paper, pushing levels from around 310 to about 510 ng/dL, squarely into healthy young man range, with DHT and estradiol rising as expected. The symptoms did not follow. Energy, sexual symptoms and mood were no better on testosterone than on placebo, and the trial had over 90 percent power to catch even a moderate benefit. Of 22 quality of life measures, exactly one favored testosterone, which the authors called noise wearing a lab coat. Dr. Jordan Feigenbaum and Dr. Austin Baraki of Barbell Medicine use this result as the backbone of their book Signal and their four part series on what a testosterone number actually means.

Who treatment is actually for

A real diagnosis needs symptoms plus a confirmed low blood level, not one afternoon blood draw read as red or green. The workup is broad on purpose: total and free testosterone, SHBG, LH and FSH, plus screening for the conditions that mimic deficiency such as anemia, thyroid disease, iron deficiency, heavy alcohol use and sleep apnea. It also has to locate the problem. Primary deficiency means the testes have failed and usually needs lifelong replacement. Secondary deficiency, where the brain is not sending the signal, is now the common pattern, driven by visceral fat, poor sleep, opioids and prior anabolic steroid use, and it is often reversible.

Overtreated and undertreated at once

Testosterone prescriptions in the United States have quadrupled or more over 20 years. A quarter of men starting therapy had no testosterone level drawn in the prior year, and half get no follow up labs afterward. The HIM study found nearly 40 percent of middle aged men had a level below 300 ng/dL, but once you require matching symptoms the real prevalence drops to 2 to 6 percent. Among men who were tested, roughly 1 in 5 got a prescription without meeting criteria. At the same time, only about 1 in 10 genuinely deficient men are treated, and high risk groups like chronic opioid users are rarely checked. A 2013 FDA safety warning and a wave of AndroGel lawsuits, more than 25,000 claims, cut prescribing by more than half between 2013 and 2016.

Dosing and monitoring

If treatment is warranted, the guidelines aim for the middle of the range, about 450 to 600 ng/dL measured halfway between doses. A man at 550 is treated correctly. A man at 1,200 is being juiced. The optimize you to 900 pitch assumes higher is better, which is not established. The old regimen of 200 mg every two weeks cannot hold a steady level, spiking near 1,400 and then cratering. Most men now take one or two injections a week, though a real world study of over 9,000 men found average levels near 800, close to the top of the range. The VA found only 3 percent of men got the full recommended workup first.

Heart

Observational studies in 2013 and a 2017 imaging study raised concerns about cardiac events and non calcified plaque. The TRAVERSE trial, published in the New England Journal of Medicine in 2023, randomized more than 5,000 men aged 45 to 80 with testosterone deficiency plus heart disease or high cardiovascular risk to topical testosterone or placebo for about two years. Cardiac events were near identical, around 7 percent in both groups. There was a small increase in atrial fibrillation and pulmonary embolism. The catch is that the treatment group only reached about 375 ng/dL, well below the guideline target, so this reassures for gentle topping up, not for a 35 year old injecting to 900.

Prostate

The prostate fear dates to a 1941 study where castration shrank tumors and testosterone regrew them. The saturation model offers an explanation: once the androgen receptors in the prostate are saturated, more testosterone does not keep driving PSA up, and PSA plateaus even at higher levels. The testosterone trials and TRAVERSE found near identical prostate cancer rates versus placebo. New data complicates the old fear in the other direction. A 2026 study of over 900 men on active surveillance found those with low baseline testosterone had a 61 percent higher chance of progressing to aggressive high grade disease, and a study of 850 men after radical prostatectomy found lower recurrence in those given testosterone. PSA should still be monitored, with attention to levels above 3 to 4 or a rising trajectory.

Fertility and blood

Exogenous testosterone shuts down FSH and LH, so the testes stop making both testosterone and sperm. It is one of the leading medically induced causes of male infertility, yet a quarter of surveyed urologists wrongly believed it improves fertility. Recovery after stopping runs 6 to 12 months and occasionally never returns. Men who want children should hear this before the first dose, and hCG or clomiphene can preserve fertility. Separately, up to 20 percent of men on injectable testosterone develop erythrocytosis, thicker blood from extra red cell production, so hematocrit is monitored and 54 percent is the threshold to investigate.

Bottom line

Testosterone is an output, a readout of sleep, body composition and overall health. Mark, the case that opened the series, walked out of a wellness clinic with a 240 level and weekly injections and felt worse by month three. His real problem was severe sleep apnea plus visceral fat. After a CPAP machine, training and better food, he came off testosterone and his own levels recovered. Confirm the low number, find what is driving it down, fix that first, and save replacement for the men who genuinely need it.