TRT Testing: How It Works, Diagnosis, Labs, and the First 90 Days

Most men who come in with questions about testosterone are not trying to reinvent themselves. They want to understand why their energy feels thin, why their interest in intimacy has faded, or why their focus slips in ways they cannot explain. They want clarity. They want to know whether something has shifted inside their bodies or whether this is simply what middle age feels like.

Testosterone replacement therapy, or TRT, sounds simple in advertisements, but the real process is more careful and thoughtful than quick messaging suggests.

Before any treatment begins, there has to be a correct diagnosis. Hormones affect nearly every system in a man’s body. When testosterone falls, the signs can overlap with thyroid issues, sleep apnea, depression, diabetes, chronic stress, and medications that blunt libido or energy. A single blood test does not answer all of this. A proper diagnosis is like piecing together a map. Each clue matters. Measuring testosterone levels, including serum testosterone and serum testosterone levels, is a critical step in the diagnostic process.

We start with the man’s story. A patient may say, “I feel drained no matter how much I sleep.” Another says, “My interest in sex is not gone, but it is weaker than it should be.” Someone else says, “My concentration has slipped and I cannot explain it.” These are familiar concerns, but they are not enough to point to hormones by themselves. Many conditions can mimic low testosterone. The job is sorting out what belongs.

That work begins with morning labs. Testosterone peaks early in the day and falls gradually. Without morning tests, the results can be misleading. Two separate morning tests give a clearer picture. But even morning testosterone levels are only the start. Free testosterone, the portion the body can use, often matters as much as the total. Sex hormone binding globulin affects how much free testosterone remains available. It is also important to measure total testosterone and bioavailable testosterone to get a complete picture of androgen status. Luteinizing hormone and follicle stimulating hormone reveal whether the problem begins in the testes or the pituitary. The pituitary gland plays a central role in regulating testosterone production, and pituitary dysfunction can contribute to androgen deficiency. Hematocrit is checked because testosterone can stimulate the bone marrow. PSA is measured because the prostate responds to hormonal changes.

Many clinics skip these steps. They run a basic screen, declare it low or borderline, and send the patient out with a prescription. This makes the process look simple, but it strips away the nuance required to understand what is really going on.

When I did my own comparison shopping years ago, the contrast was striking. At Men’s Health Boston, the laboratory workup was not a single number. It included DHEA, Free T4, total and free testosterone, LH, FSH, SHBG, estradiol, progesterone, prolactin, TSH, PSA and zPSA, hematocrit, and IGF-1 by LC/MS. Each of these tests adds another dimension. Thyroid status, pituitary signaling, estrogen balance, growth factors, prostate markers, and red cell production all influence how a man feels. They also shape how he should be treated. Evaluating bone mineral density and reduced bone mineral density is also important, especially in men with symptoms of low testosterone or at risk for decreased bone density. That kind of lab panel is not excessive. It is how a physician distinguishes a simple screening value from a true diagnosis. A single testosterone number is not the whole story. Sometimes the story is more complicated and these markers help reveal it. The significance of the European Male Aging Study and Massachusetts Male Aging Study lies in their contributions to understanding the prevalence and epidemiology of androgen deficiency and low testosterone in aging men.

When the diagnosis is clear and the cause is understood, we talk about treatment. TRT is meant to restore testosterone to a healthier range for men who are genuinely low. But there are several ways to deliver the hormone, and the differences between them matter.

Injections are often the first method men hear about. They act fast and are usually covered by insurance. A man may feel a surge in the first day or two. Then levels begin to fall and by the end of the week he may feel the dip. One patient described it well. “Mondays feel great. Fridays feel slow.” The pattern repeats each week. Some men do fine with this rhythm. Others find the swings distracting.

Gels offer daily dosing. They avoid the sharp peaks of injections, but they still fluctuate. Absorption varies with skin type, activity, humidity, and contact with others. They are simple to apply but not always predictable. Testosterone gel is a commonly used form of testosterone therapy, providing a convenient application and stable pharmacokinetics for many patients.

Synthetic pellets release testosterone more gradually than injections or gels, but they remain chemically altered forms made for patent purposes. They work, but they are not identical to natural testosterone.

Bioidentical pellets are different. They match the molecular structure of the testosterone men produce naturally. Once inserted, the pellet releases hormone slowly. Levels do not spike or crash. There is a steadiness men often describe as calming. It feels more like their physiology and less like a weekly cycle of highs and lows.

Regardless of the delivery method, TRT works in stages. There is no sudden jolt. The first thirty days often bring a lift in mood and desire. A man may feel more engaged. He wakes with a clearer sense of direction. He finds himself thinking about intimacy again rather than ignoring it. These early changes matter, even if they are small.

Between thirty and sixty days, physical improvements begin. Workouts feel easier to start and easier to recover from. A man does not feel as though he is dragging himself through the day. He can push a bit harder and not pay for it the next morning.

By ninety days, the broader picture appears. Fat around the midsection begins to ease. Muscle tone improves. Improvements in lean body mass and muscle strength are well-documented benefits of testosterone treatment. Focus sharpens. Fatigue lifts. One man described it this way. “Nothing dramatic. It is just smoother. Life does not grind me down the way it did.” Another said, “It feels like the lights came back on.” There is also potential for significant reduction in fat mass, but patients should be aware of the increased risk of certain side effects, such as cardiovascular disease and heart disease, which require ongoing monitoring.

During these first months, monitoring is essential. Testosterone can raise hematocrit. PSA must be watched. The dose may need adjustment. The physician’s role is not only guiding therapy but ensuring that the body responds safely. Monitoring prostate specific antigen is especially important to screen for prostate cancer risk during testosterone therapy.

Fertility deserves discussion before treatment begins. When testosterone enters from outside, the body reduces its own signals to produce it. Sperm production can fall. A man planning for children must know this early. Alternatives like clomiphene or hCG can preserve fertility in the right circumstances. These options depend on planning and proper timing. Leydig cell function is also crucial, as it supports both testosterone and sperm production.

Some men ask if TRT is lifelong. It depends on the cause. If the body has lost its ability to produce testosterone, long term therapy may be appropriate. If the deficiency is secondary to a reversible problem, TRT may be tapered later. Acute illness, obstructive sleep apnea, and normal aging can all contribute to symptoms of low testosterone and should be considered before starting therapy. These decisions must be guided by evidence, not fear or assumptions.

Commercial TRT centers often skip nuance, which leaves men confused about why they feel better at first but poorly managed later. Good TRT does not emphasize speed. It emphasizes accuracy. It takes the time to understand the man, confirm the diagnosis, explain the choices, and follow through. TRT is not a youth serum. It is a correction of imbalance for men who have lost too much of their natural signal. Clinicians should focus on restoring normal levels of the male sex hormone and addressing certain symptoms, such as decreased frequency of sexual thoughts, body hair loss, and breast symptoms.

When done correctly, TRT brings a man back to his baseline. Not the baseline he had at twenty, but the one where his days feel manageable and meaningful. Where he can think clearly. Where he has interest in intimacy. Where his energy does not fade before the work is done.

One patient said it best. “I did not want to be a new man. I just wanted to feel like myself again.” That is the purpose of TRT. To restore, not to reinvent. Identifying the three sexual symptoms most strongly associated with late-onset hypogonadism and distinguishing between normal aging and pathological androgen deficiency are essential parts of this process.