How Does Testosterone Replacement Therapy Work?

Men who are about to start testosterone therapy usually want to know two things: what the treatment actually does in the body, and how long it will take before they notice a difference. The second question matters more than people expect, because testosterone does not change everything at once. Some effects show up within weeks, while others build slowly over a year or more.

Knowing the sequence makes the first months of treatment easier to read, and helps explain why your clinician checks certain blood tests when they do.

What testosterone does once it is in your body

Testosterone works by attaching to androgen receptors, which are found in many tissues, including muscle, bone, skin, the brain and the sex organs. When the hormone binds to a receptor, it switches on genes that shape how that tissue grows and behaves. That is why low testosterone can show up in such different ways, from low libido to loss of muscle.

Part of the testosterone in your body is also converted into two other hormones. An enzyme called 5-alpha reductase turns some of it into DHT, a stronger androgen that affects the prostate, skin and hair. Another enzyme, aromatase, turns some into estradiol, a form of estrogen that men need too, for bone among other things. Treatment raises all three, which is one reason your clinician looks at more than your testosterone number. If hair loss is a concern, our article on finasteride and TRT covers how DHT fits in.

Why your own production slows down

Your brain keeps track of how much testosterone is in your blood. When levels are low, the pituitary gland releases two hormones, LH and FSH, that tell the testes to make more testosterone and to produce sperm. When testosterone comes from treatment, the brain reads the higher level and turns those signals down.

The result is that your testes make less testosterone of their own and fewer sperm. For most men on TRT this is expected and is the reason treatment is usually long-term, since it replaces testosterone rather than restarting your own production. It also means that men who want to have children soon should say so before starting, because testosterone therapy reduces fertility.

What changes, and when

A review that pulled together the published research on the timing of testosterone’s effects found a fairly consistent pattern, although most of the studies were not designed to measure timing, and individual men vary.

Sexual interest is usually the first thing to change, with effects appearing after about three weeks and reaching their peak by around six weeks. Improvements in erections and ejaculation can take longer, up to six months. Quality of life tends to start shifting within three to four weeks, and improvements in low mood become noticeable after three to six weeks, continuing to build for several months.

Changes in the body take longer. Fat mass, lean mass and muscle strength start to change within 12 to 16 weeks and generally level off between six and twelve months. Effects on bone can be measured after about six months and continue for at least three years. Testosterone also raises red blood cell production, with the effect visible at around three months and peaking at nine to twelve months.

Not every change people hope for shows up in clinical trials. For an overview of which benefits large studies have confirmed and which they have not, read what the trials show about the benefits of TRT.

Getting the dose right

The aim of treatment is to bring testosterone into the middle of the normal range, not as high as possible. Your clinician adjusts the dose based on how you feel and on blood tests, and the timing of those tests depends on the form of testosterone you use. With a gel, for example, levels are usually checked a few hours after you apply it.

The timeline above also explains the monitoring schedule. Because the effect on red blood cells appears at around three months, hematocrit is checked before treatment and again three to six months after starting, and then at regular intervals. The Endocrine Society guideline recommends reviewing symptoms, side effects and labs within the first year, and then annually once things are stable. You can read more in what the Endocrine Society guidelines say about TRT.

Starting TRT at SaltMD

Treatment starts with a 30-minute consultation about your symptoms, health history and plans for children, in person in Atlanta or by video. Your hormone panel can be drawn at a lab near you or at our office, or your clinician can review blood work you have had in the past 90 days. If your results confirm low testosterone and treatment makes sense for you, your prescription is filled by a partner pharmacy and shipped to you, and follow-up labs keep your levels on track from there.

Learn more about testosterone replacement therapy at SaltMD.

Sources

• Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011;165(5):675-685. doi:10.1530/EJE-11-0221
• Bhasin S et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. doi:10.1210/jc.2018-00229