Short answer: Low testosterone is diagnosed from symptoms plus at least two low morning testosterone tests, per the Endocrine Society and AUA guidelines. Testosterone cypionate and enanthate are FDA approved for it. In the TRAVERSE trial of 5,246 men, heart events were 7.0% on testosterone vs 7.3% on placebo. The labels ask for regular hematocrit and blood pressure checks, so doses, timing and labs are worth logging.
| Compound | Best evidence | What it shows |
|---|---|---|
| Testosterone cypionate (Depo-Testosterone) | FDA-approved for this | FDA approved as replacement therapy in men with primary hypogonadism or hypogonadotropic hypogonadism. The label says safety and efficacy in age-related low testosterone are not established. |
| Testosterone enanthate (generic, Xyosted) | FDA-approved for this | Same approved use. In the Xyosted trials, hematocrit reached 55% or higher in 12 of 283 men (4.2%). |
| hCG (Novarel, Pregnyl) | FDA-approved for this | The Novarel label approves it in males for selected cases of hypogonadotropic hypogonadism (low testosterone caused by the pituitary) and for prepubertal cryptorchidism. |
| Enclomiphene | Human trials | Raised testosterone and LH with sperm counts conserved in a phase 2 trial, but it is not FDA approved. |
| Clomiphene (Clomid) | Approved for a different use | Approved only for ovulation problems in women. The Endocrine Society notes its efficacy and safety in men have not been shown in randomized trials. |
"Animal or lab studies only" means no published human trial for this goal that we could find. Results in rats or cells often do not carry over to people. Compounds that are not FDA-approved have no tested label for dose, purity or safety.
The Endocrine Society 2018 guideline recommends diagnosing hypogonadism (low testosterone) only in men who have both symptoms or signs of deficiency and clearly, consistently low testosterone. The first test is a fasting morning total testosterone with an accurate assay, and the guideline says to confirm it by repeating that morning test. When total testosterone is near the low end of normal, or a condition changes sex hormone-binding globulin (SHBG, the protein that carries testosterone in blood), it advises checking free testosterone too.
The AUA 2018 guideline uses a total testosterone below 300 ng/dL as a reasonable cut-off, measured twice on separate early mornings. The Depo-Testosterone and testosterone enanthate labels say the same thing in their own words: confirm low testosterone with morning levels on at least two separate days before starting.
Both guidelines also say to look for a cause once low testosterone is confirmed. The AUA guideline says to measure LH (the pituitary signal to the testes) in men with low testosterone, and prolactin when LH is low or low-normal.
The Testosterone Trials (TTrials) gave testosterone gel or placebo for 1 year to 790 men aged 65 or older with testosterone below 275 ng/dL and symptoms. Testosterone improved sexual activity, sexual desire and erectile function, and slightly improved mood. It did not improve vitality (energy) scores, and walking distance improved only when all three trials were pooled (20.5% vs 12.6% walked at least 50 m farther).
TRAVERSE was the large heart-safety trial. It enrolled 5,246 men aged 45 to 80 with heart disease or high heart risk, symptoms, and two fasting testosterone levels under 300 ng/dL. Over a mean follow-up of 33 months, the main heart outcome (heart death, nonfatal heart attack or nonfatal stroke) happened in 7.0% on testosterone gel and 7.3% on placebo (hazard ratio 0.96). That met the bar for "not worse than placebo." Atrial fibrillation, acute kidney injury and pulmonary embolism were more common in the testosterone group.
TRAVERSE used a daily gel, not injections, so its results describe gel. The labels for Xyosted note this too.
In February 2025, FDA told makers of all testosterone products to add the TRAVERSE results to their labels and to remove the boxed warning language about increased heart risk. FDA also required blood pressure information or a new warning about raised blood pressure, because its ambulatory (24-hour) blood pressure studies found increases across the class. Xyosted, which had a boxed warning about blood pressure increases, lists that boxed warning as removed in March 2025.
The Endocrine Society also advises against starting testosterone in men planning a pregnancy soon, or with breast or prostate cancer, a high hematocrit, untreated severe sleep apnea, uncontrolled heart failure, or a heart attack or stroke in the last 6 months, among other conditions.
The Endocrine Society suggests aiming for testosterone in the mid-normal range and monitoring symptoms, side effects, testosterone, hematocrit and prostate cancer risk during the first year. The AUA guideline says to recheck testosterone every 6 to 12 months once levels are stable. For cypionate or enanthate it says to test no earlier than three to four injection cycles in, and it says to discuss stopping if levels are normal after 3 to 6 months but symptoms have not improved.
Because injected testosterone rises and falls between shots, when blood is drawn relative to the last injection changes the number. See how TRT reaches steady state and weekly vs twice-weekly injections.
Terms on this page: Testosterone ester · Hematocrit · Steady state · Trough level