TRT Complete Guide: Everything You Need to Know
Testosterone replacement therapy can be transformative for men with clinically low testosterone—but it's a long-term commitment with real considerations. This guide covers who qualifies, how it works, what to expect, and what the research says about benefits and risks.
In This Guide
What Is Testosterone Replacement Therapy?
Testosterone replacement therapy (TRT) is a medical treatment that supplements the body's natural testosterone production. It's prescribed for men whose bodies don't produce enough testosterone on their own—a condition called hypogonadism.
The goal of TRT isn't to boost testosterone beyond normal levels. It's to restore testosterone to a healthy range, typically 300-1000 ng/dL, to relieve symptoms caused by deficiency.
TRT is available in several forms: injections, topical gels, patches, pellets, and nasal sprays. Each has advantages and disadvantages, which we'll cover in detail.
Who Qualifies for TRT?
The FDA has approved TRT specifically for men with hypogonadism—low testosterone caused by a medical condition affecting the testes, pituitary gland, or hypothalamus. This includes:
- • Primary hypogonadism: The testes themselves don't produce enough testosterone (due to injury, infection, genetic conditions like Klinefelter syndrome, or cancer treatment)
- • Secondary hypogonadism: Problems with the pituitary gland or hypothalamus that signal testosterone production (tumors, inflammatory diseases, medications)
Important Distinction
The FDA has not approved TRT for the natural decline in testosterone that occurs with aging ("age-related" or "late-onset" hypogonadism). However, many physicians do prescribe TRT for symptomatic men with low testosterone regardless of cause, based on clinical judgment.
To qualify for TRT, you typically need:
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Low testosterone confirmed by blood test
Two separate morning blood tests (between 8-10am when T is highest) showing levels below 300 ng/dL, taken at least one week apart.
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Symptoms of low testosterone
A low number alone isn't enough—you should have symptoms like low libido, erectile dysfunction, fatigue, depression, loss of muscle mass, or decreased bone density.
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No contraindications
TRT is not appropriate for men with prostate cancer, breast cancer, severe heart failure, untreated sleep apnea, or very high red blood cell counts.
Getting Diagnosed: The Testing Process
A proper diagnosis involves more than just checking testosterone levels. Your provider should:
Blood Tests
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Total testosterone: Primary measure. Two morning tests required.
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Free testosterone: Measures unbound testosterone. Important if SHBG is suspected to be abnormal.
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LH and FSH: Help determine if the problem is in the testes (primary) or pituitary/hypothalamus (secondary).
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Prolactin: Elevated levels can suppress testosterone production.
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CBC (complete blood count): Baseline before starting TRT to monitor for polycythemia.
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PSA: Prostate-specific antigen baseline for men over 40.
Ruling Out Other Causes
Your provider should investigate whether something treatable is causing your low testosterone: obesity, sleep apnea, diabetes, thyroid disease, certain medications, or chronic illness. Addressing these underlying issues sometimes normalizes testosterone without needing TRT.
TRT Treatment Options
Testosterone can be delivered several ways, each with pros and cons:
Testosterone Injections
Advantages
- • Most cost-effective option
- • Highly effective at raising T levels
- • Flexible dosing schedules
- • Can self-administer at home
Disadvantages
- • Levels fluctuate (peak and trough)
- • Requires needles
- • Injection site reactions possible
- • Weekly or bi-weekly schedule
Common forms: Testosterone cypionate, testosterone enanthate. Typical dosing: 100-200mg every 1-2 weeks.
Topical Gels (AndroGel, Testim)
Advantages
- • Stable, steady T levels
- • No needles
- • Easy daily application
- • Mimics natural daily rhythm
Disadvantages
- • More expensive than injections
- • Risk of transfer to others (skin contact)
- • Must apply daily
- • Skin irritation possible
Applied daily to shoulders, upper arms, or abdomen. Must avoid skin contact with women and children after application.
Testosterone Patches (Androderm)
Advantages
- • Consistent T levels
- • Easy to use
- • Less transfer risk than gels
Disadvantages
- • Skin irritation common (up to 60%)
- • Visible patch
- • May not adhere well with sweating
Applied nightly to back, abdomen, upper arms, or thighs. Rotate application sites.
Testosterone Pellets (Testopel)
Advantages
- • Long-acting (3-6 months)
- • Steady T levels
- • No daily/weekly maintenance
Disadvantages
- • Requires office procedure
- • Risk of pellet extrusion
- • Less flexible if dose adjustment needed
Small pellets implanted under the skin (usually buttocks) every 3-6 months.
Nasal Gel (Natesto)
Advantages
- • No skin transfer risk
- • May preserve fertility better
- • Fast absorption
Disadvantages
- • Three times daily dosing
- • Nasal irritation possible
- • More expensive
Applied inside the nose three times daily. Unique pulsatile delivery may have less impact on fertility.
Benefits of TRT
For men with genuinely low testosterone, TRT can provide significant improvements in multiple areas:
Sexual Function
Improved libido (usually noticeable within 3-6 weeks), better erectile function (may take up to 6 months for maximum benefit), and increased sexual satisfaction.
Energy & Mood
Many men report improved energy levels, better mood, reduced depressive symptoms, and better overall sense of well-being within the first few weeks.
Body Composition
Increased lean muscle mass, reduced body fat (particularly abdominal), and improved strength. Changes are gradual over 3-12 months.
Bone Density
TRT can increase bone mineral density and reduce osteoporosis risk. Effects on bone take 6-12 months or longer to manifest.
Cognitive Function
Some studies suggest improvements in memory, concentration, and mental clarity, though evidence is mixed.
Metabolic Health
May improve insulin sensitivity and metabolic markers, particularly beneficial for men with metabolic syndrome or type 2 diabetes.
Risks & Side Effects
TRT isn't without risks. Understanding these is crucial before starting treatment:
Common Side Effects
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Polycythemia (high red blood cell count): Occurs in over 20% of men on TRT. Increases blood viscosity and potentially clotting risk. Requires regular monitoring.
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Testicular shrinkage: External testosterone signals the body to reduce its own production, causing testes to shrink.
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Acne and oily skin: Increased sebum production. Usually manageable.
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Fluid retention: Ankle swelling, weight gain from fluid. Usually mild.
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Sleep apnea worsening: TRT can worsen existing sleep apnea or unmask undiagnosed cases.
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Gynecomastia: Breast tissue growth due to testosterone converting to estrogen. May require dose adjustment or additional medication.
Cardiovascular Risk: The Updated Picture
Cardiovascular safety has been TRT's most controversial topic. Here's where the evidence stands:
The TRAVERSE Trial (2023)
The largest TRT cardiovascular safety trial to date (5,246 men, median follow-up 33 months) found no increased risk of major cardiovascular events (heart attack, stroke, cardiovascular death) compared to placebo. This led the FDA to remove its cardiovascular warning from testosterone products in February 2025.
However, the TRAVERSE trial did find higher rates of:
- • Atrial fibrillation (irregular heartbeat)
- • Blood clots (deep vein thrombosis, pulmonary embolism)
- • Kidney problems
Prostate Safety
Current evidence shows TRT does not increase prostate cancer risk in men without existing cancer. However, TRT can stimulate growth of existing prostate cancer, which is why it's contraindicated in men with prostate cancer and why PSA monitoring is required.
Required Monitoring
TRT requires ongoing monitoring to ensure safety and effectiveness:
Typical Monitoring Schedule
First 3-6 months
Blood tests at 1 month, 3 months, then every 6-12 months. Checking testosterone levels, hematocrit (red blood cells), PSA, and liver function.
Ongoing
Every 6-12 months: testosterone, hematocrit, PSA (for men over 40), lipid panel, and symptom assessment.
Action thresholds
Hematocrit >54%: dose reduction or blood donation may be needed. PSA increase >1.4 ng/mL in 12 months or >4.0 total: requires urological evaluation.
What to Expect: The TRT Timeline
TRT effects don't happen overnight. Here's a realistic timeline based on clinical research:
Weeks 1-4
Energy, mood, and sense of well-being may begin improving. Some men notice changes in libido.
Weeks 3-6
Sexual function (libido, erection quality) typically begins improving. May plateau at 3-6 weeks.
Months 2-3
Metabolic effects begin. Red blood cell production increases (monitor hematocrit).
Months 3-6
Body composition changes become noticeable—increased muscle mass, decreased fat. Erectile function continues improving.
Months 6-12
Maximum benefits for muscle, bone density, and body composition. Bone density improvements continue up to 3 years.
TRT and Fertility: A Critical Consideration
Important Warning
TRT significantly reduces sperm production and can cause infertility. The NIH states plainly: "Testosterone should not be used for men seeking to produce a pregnancy."
When you take external testosterone, your brain senses adequate hormone levels and signals the pituitary to stop producing LH and FSH—the hormones that stimulate sperm production. The result: drastically reduced or absent sperm.
Recovery after stopping TRT is possible but not guaranteed:
- • About 2/3 of men recover sperm production within one year of stopping
- • About 10% may never recover sperm production
- • If future fertility is desired, consider sperm banking before starting TRT
- • Alternatives like clomiphene or hCG may preserve fertility while treating symptoms
Can You Stop TRT?
Yes, you can stop TRT, but there are important considerations:
When you stop TRT, your body needs time to restart its own testosterone production. During this period (which can take weeks to months), you'll likely experience a return of low-T symptoms—often worse than before because your natural production hasn't yet recovered.
Whether your testosterone levels recover depends on what caused your low T in the first place:
- • Primary hypogonadism: If your testes are damaged, they may not recover—you may need lifelong TRT.
- • Secondary hypogonadism: Better chance of recovery, especially if the underlying cause is addressed.
- • Age-related decline: Your levels will likely return to where they were—which was low enough to cause symptoms.
Most men who start TRT and find it beneficial continue indefinitely. It's meant to be a long-term therapy.
Ready to Explore TRT?
Online telehealth platforms make it easy to get testosterone levels tested, consult with licensed providers, and start treatment if appropriate—all from home.
The Bottom Line
TRT can be life-changing for men with genuine hypogonadism, improving energy, mood, sexual function, body composition, and quality of life. However, it's a long-term commitment that requires ongoing monitoring and comes with real side effects and fertility implications. The decision to start TRT should be made carefully with a knowledgeable provider who can properly diagnose your condition, rule out other causes, and monitor your treatment.