Testosterone replacement therapy is typically appropriate when you have both a confirmed blood level below 300 ng/dL and symptoms that affect your daily life, such as low sex drive, persistent fatigue, or loss of muscle mass. Neither low numbers alone nor symptoms alone are enough. The decision involves lab work, screening for conditions that rule out therapy, and a conversation about your goals, particularly around fertility.
The 300 ng/dL Threshold
The American Urological Association considers a total testosterone level below 300 ng/dL the diagnostic cutoff for low testosterone. Other major medical societies use slightly different numbers, ranging from 230 to 350 ng/dL, but 300 ng/dL is the most widely referenced standard in the United States.
Testosterone naturally declines by roughly 1% per year after age 30. Normal adult levels span a wide range, from 300 to 1,000 ng/dL. That means a 55-year-old man sitting at 310 ng/dL is technically “normal” but may feel very different from how he felt at 600 ng/dL a decade earlier. This is part of why symptoms matter as much as the number itself.
To get an accurate reading, blood draws need to happen in the early morning, when testosterone peaks. Guidelines require at least two separate morning tests showing levels at or below 300 ng/dL before a diagnosis is made. A single low reading isn’t enough, since levels fluctuate day to day based on sleep, stress, illness, and other factors.
Symptoms That Support a Diagnosis
A low number on a lab report doesn’t automatically mean you need treatment. Therapy is considered when that number lines up with symptoms you’re actually experiencing. The core symptoms include:
- Low sex drive or erectile dysfunction
- Persistent fatigue or lethargy
- Loss of muscle mass and strength
- Depressed mood or difficulty concentrating
- Increased body fat, especially around the midsection
- Reduced bone density
Many of these overlap with other conditions like depression, poor sleep, or thyroid problems. That’s why doctors are supposed to investigate other explanations before attributing everything to low testosterone. It’s also worth knowing that some of these symptoms, particularly low libido and concentration problems, are things men often don’t bring up on their own. If you suspect low testosterone, mention these specifically.
Lab Work Before You Start
Before therapy begins, a set of baseline blood tests helps your doctor determine whether treatment is safe and which type of low testosterone you have. The standard pre-treatment panel includes:
- Total testosterone (two morning draws, same lab, same test method)
- Luteinizing hormone (LH), which helps distinguish whether the problem originates in the testes or the brain’s signaling system
- Hematocrit, a measure of red blood cell concentration in your blood. If your baseline is already above 50%, therapy carries a higher risk of thickening your blood to dangerous levels.
- PSA (prostate-specific antigen) for men over 40, to screen for prostate issues before adding testosterone
- Prolactin, checked when LH is low or borderline, to rule out a pituitary gland issue such as a benign tumor called a prolactinoma
If LH levels come back low alongside low testosterone, that suggests the brain isn’t properly signaling the testes to produce testosterone. This pattern can point to a pituitary problem that may need its own treatment, potentially making TRT unnecessary if the underlying cause is correctable. Your doctor should also check for breast tenderness or enlargement before starting, since testosterone can worsen that in some men.
Who Should Not Start TRT
Certain conditions rule out testosterone therapy entirely. Men with untreated prostate cancer or breast cancer should not receive it. Men considered high-risk for prostate cancer, including those with a first-degree relative who had it or African-American men with an elevated PSA above 3 ng/mL, need careful evaluation before proceeding.
A hematocrit above 50% is a relative contraindication under American guidelines, while European guidelines draw the hard line at 54%. The concern is polycythemia, a condition where blood becomes too thick and raises the risk of clots, stroke, or heart attack. If hematocrit rises above 54% during treatment, therapy should be paused until levels normalize. Once they drop below 50% and no other cause is found, treatment can sometimes restart at a lower dose.
Untreated obstructive sleep apnea is also a relative contraindication. If you snore heavily or wake up unrefreshed, that should be evaluated before starting testosterone.
Fertility Is a Major Decision Point
This is one of the most important and most overlooked considerations. Testosterone therapy suppresses sperm production, often severely. Studies show that 65% of men with normal sperm counts develop azoospermia (zero sperm) within four months of starting treatment. Rates as high as 75% have been documented within six months, and some formulations push that figure above 90%.
If you want to have children now or in the future, this needs to be part of the conversation before you start. Sperm production often recovers after stopping therapy, but not always, and recovery can take a year or more. Options to preserve fertility include banking sperm before starting, or using alternative medications that raise testosterone without shutting down sperm production. Clomiphene citrate stimulates your body to make more testosterone on its own while keeping the testes active. Human chorionic gonadotropin (hCG) works similarly and is sometimes used alongside TRT to maintain testicular function and sperm production.
What Changed With Cardiovascular Risk
For nearly a decade, cardiovascular safety was the biggest cloud hanging over testosterone therapy. In 2014, the FDA issued a safety warning about increased reports of stroke, heart attack, and death in men using testosterone products. That warning was serious enough to require a boxed warning on all testosterone labels.
The picture shifted significantly after the TRAVERSE trial, a large study submitted to the FDA in 2023, which found no increase in adverse cardiovascular outcomes among men using testosterone for diagnosed low levels. Based on those results, the FDA removed the cardiovascular boxed warning from testosterone products. However, the FDA simultaneously added new warnings about increased blood pressure, which should be monitored during treatment.
Monitoring After You Start
Starting therapy isn’t a one-time decision. It requires ongoing blood work to make sure levels are responding appropriately and side effects aren’t developing. Hematocrit is the most important safety marker to track, given the blood-thickening risk. PSA continues to be monitored in men over 40. Testosterone levels themselves are rechecked to confirm the dose is putting you in the target range without pushing too high.
Most monitoring schedules call for blood work within the first few months of starting, then at regular intervals during the first year. After that, testing typically continues at least annually. Your doctor will also watch for symptoms like breast tenderness, mood changes, or worsening sleep apnea, all of which can signal a need to adjust or stop treatment.
The Bottom Line on Timing
The right time to start is when three things align: your testosterone is consistently below 300 ng/dL on properly timed morning blood draws, you have symptoms that match, and screening has ruled out conditions that make therapy unsafe or unnecessary. If a correctable cause exists, like a pituitary issue or a medication side effect, treating that comes first. If fertility matters to you, alternative approaches should be explored before defaulting to testosterone. The decision is rarely urgent, which means taking the time to get complete lab work and weigh your options is almost always the right move.