What do randomized trials show so far?
The randomized evidence covers years, not decades, and on the big questions it is reassuring. TRAVERSE, the largest trial, enrolled men aged 45 to 80 with low testosterone and heart disease or high heart risk. Major cardiovascular events occurred in about 7.0% of men on testosterone and 7.3% on placebo.
The Endocrine Society’s 2026 statement summarizes TRAVERSE as showing no meaningful increase in heart attack and stroke over one to four years, but roughly a 50% relative increase in pulmonary embolism. A fracture analysis from the same trial found clinical fractures in 3.50% of men on testosterone versus 2.46% on placebo. Prostate events were low and similar between groups.
Regulators responded: in 2025 the FDA removed boxed warning language about adverse cardiovascular outcomes from testosterone labels and added a blood pressure warning.
What do registries with five-plus years show?
Registries follow men far longer than trials, but they cannot prove cause. One widely cited registry study followed 316 men with low testosterone and prediabetes for eight years. The 229 men who received testosterone injections saw average HbA1c fall, while 40.2% of the 87 untreated men progressed to type 2 diabetes. Deaths were 7.4% in the treated group and 16.1% in the untreated group.
Those are striking numbers, but the men chose whether to be treated, the study came from a single registry and the groups were not randomized. Men who accept treatment may differ in health habits from men who decline it. Registry data should be read as encouraging signals that still need confirming, not as proof of long-term benefit or safety.
What is still unknown?
Several things are still unknown, and the Endocrine Society says so plainly. Its 2026 statement says long-term safety, including for prostate cancer, remains unestablished, notes that prostate cancer develops slowly and that trials may not have followed men long enough, and calls for a long-term research program on men’s health.
The open questions include cardiovascular and prostate outcomes past five to ten years, what the fracture finding in TRAVERSE means in practice, and how results apply to men younger than those studied.
Which effects add up over a decade of treatment?
The effects that accumulate are mostly ones labs and checkups can catch:
| Effect | What happens over time | How it is watched |
|---|---|---|
| Hematocrit | Red cell count can climb and stay high | The Endocrine Society guideline checks at baseline, 3 to 6 months, then yearly, and stops therapy above 54% until it falls |
| Blood pressure | Small average rises, larger in some men | Readings at visits; now a class-wide label warning |
| PSA and prostate | Small expected rise in year one, then the usual drift with age | Thresholds that trigger urology review |
| Fertility and testicular size | Sperm production and testicular volume stay suppressed on treatment | Discussed at the start; HCG when fertility matters |
| Sleep apnea | Can appear or worsen, especially in men with risk factors | Symptom questions and sleep studies when needed |
| Clots | Pulmonary embolism signal in TRAVERSE | Knowing warning signs, reviewing risk factors |
Our pages on blood clot warning signs on TRT and how often blood work is needed on TRT go into two of these rows. For a broader view of the trade-offs, see the downsides of TRT.
How Ultimate Male monitors long-term TRT
Long-term safety at Ultimate Male rests on not letting monitoring lapse. Follow-up labs drawn at San Gabriel or Downey track hematocrit, PSA, estradiol and testosterone, blood pressure is checked at visits, and the reason you are on treatment is revisited, since some men can come off, as our page on whether TRT is for life explains.
Sudden shortness of breath or chest pain means calling 911, and a painful, swollen leg needs emergency care the same day. For routine questions about long-term testosterone therapy, book a follow-up or call 626-319-5261.
