Testosterone Replacement Therapy: A Complete Guide

Testosterone replacement therapy has gone from a niche medical treatment to a mainstream conversation — and with that mainstream attention has come a lot of noise. Testosterone optimization clinics, online "men's health" mills, and social media influencers have created an environment where it's genuinely difficult to distinguish evidence-based medicine from marketing.

This guide cuts through that. Whether you're investigating TRT because of symptoms, lab results, or just curiosity, here's what the science actually says about who needs it, how it works, and what responsible treatment looks like.

Understanding Testosterone Levels

Testosterone is the primary male sex hormone, though it plays important roles in women's health too. In men, it's produced primarily by the Leydig cells in the testes, regulated by the hypothalamic-pituitary-gonadal (HPG) axis.

Normal ranges and the gray zone:

Most laboratories define the normal range for total testosterone as approximately 264-916 ng/dL, though reference ranges vary by lab. The challenge is that these ranges are based on population distributions, not individual optimization.

Key concepts:

• Total testosterone — All testosterone in the blood, including bound and unbound
• Free testosterone — The unbound, biologically active fraction (typically 2-3% of total). This is often more clinically relevant than total testosterone
• SHBG (sex hormone-binding globulin) — The protein that binds most testosterone, rendering it inactive. High SHBG can create low free testosterone despite normal total levels
• Bioavailable testosterone — Free testosterone plus albumin-bound testosterone. A useful measure of what your tissues can actually use

When levels matter and when they don't:

A total testosterone of 280 ng/dL is technically within "normal range" but may cause symptoms in a man who previously ran at 600. Conversely, a man at 350 ng/dL who feels great and has no symptoms doesn't need treatment just because his number is "low-normal."

The clinical principle: treat symptoms and clinical findings, not just numbers. Lab values inform the picture; they don't dictate the decision.

Signs and Symptoms of Low Testosterone

Low testosterone (hypogonadism) produces a constellation of symptoms that develop gradually, which is part of why men often tolerate them for years before seeking evaluation.

Physical symptoms:

• Fatigue and decreased energy
• Reduced muscle mass and strength
• Increased body fat, particularly central/visceral
• Decreased bone density (long-term)
• Hot flashes (yes, men get them too)
• Loss of body and facial hair (gradual)

Sexual symptoms:

• Decreased libido
• Erectile dysfunction
• Reduced morning erections
• Decreased ejaculate volume
• Difficulty achieving orgasm

Cognitive and emotional symptoms:

• Brain fog and poor concentration
• Depressed mood or irritability
• Decreased motivation and drive
• Poor sleep quality
• Reduced sense of well-being

The overlap problem: Many of these symptoms overlap with depression, thyroid dysfunction, sleep apnea, diabetes, and normal aging. This is why a thorough evaluation is essential — you don't want to start TRT when the actual problem is untreated sleep apnea or hypothyroidism.

Who Actually Needs TRT

The Endocrine Society guidelines recommend TRT for men with:

1. Consistently low testosterone levels — At least two morning testosterone measurements below 300 ng/dL (or below 264 ng/dL by some guidelines)
2. Symptoms consistent with hypogonadism — from the list above
3. No contraindications — see below

Types of hypogonadism:

Primary hypogonadism — The testes aren't producing enough testosterone. Causes include Klinefelter syndrome, testicular injury, mumps orchitis, and cryptorchidism. Labs show low testosterone with elevated LH and FSH (the brain is signaling the testes to produce more, but they can't).

Secondary hypogonadism — The hypothalamus or pituitary isn't signaling the testes properly. Causes include pituitary tumors, obesity, opioid use, chronic illness, and aging. Labs show low testosterone with low or inappropriately normal LH and FSH.

Functional hypogonadism — Low testosterone caused by modifiable conditions (obesity, diabetes, medication effects) that may respond to addressing the underlying cause before committing to TRT.

At CORAL, Dr. Kim evaluates the full picture before recommending TRT — because starting testosterone without understanding why it's low can mean missing a pituitary tumor or treating a medication side effect with another medication.

The Workup: What to Test and When

A proper testosterone evaluation includes more than just a testosterone level:

Essential labs:

• Total testosterone (morning draw, fasting preferred — testosterone peaks in the early morning)
• Free testosterone or SHBG (to calculate free testosterone)
• LH and FSH (to distinguish primary from secondary hypogonadism)
• Complete metabolic panel
• CBC (hematocrit — baseline before starting TRT)
• Prolactin (elevated levels can indicate pituitary issues)
• TSH (thyroid function — hypothyroidism mimics low T symptoms)

Additional labs depending on clinical scenario:

• Estradiol (E2) — especially relevant for monitoring on TRT
• PSA (prostate-specific antigen) — baseline before treatment in men over 40
• DHEA-S
• Cortisol (if adrenal insufficiency is suspected)
• Hemoglobin A1c (diabetes screening — diabetes commonly causes low testosterone)
• Vitamin D (deficiency can affect testosterone levels)

Testing protocol:

• Draw blood in the morning (before 10 AM), ideally fasting
• Confirm low levels on at least two separate occasions
• Consider variables: illness, poor sleep, stress, and medications can transiently lower testosterone

Treatment Options

Injectable Testosterone

Testosterone cypionate and testosterone enanthate — The most common and cost-effective TRT options.

• Typical dosing: 100-200 mg intramuscularly or subcutaneously every 1-2 weeks
• Some patients prefer twice-weekly injections for more stable levels and fewer side effects
• Injectable testosterone provides reliable, predictable levels
• Self-injection is straightforward after training
• Cost: typically $30-80/month

Topical Testosterone

Testosterone gel (AndroGel, Testim) and patches (Androderm)

• Applied daily
• Provides more physiological (steady-state) levels
• Transfer risk to partners and children through skin contact — requires precautions
• Some patients are poor absorbers and can't achieve adequate levels
• Cost: significantly higher than injections unless using compounded preparations

Other Options

• Testosterone pellets (Testopel) — Implanted subcutaneously every 3-6 months. Convenient but requires an in-office procedure and can be difficult to adjust if levels are too high
• Nasal testosterone (Natesto) — Applied intranasally 2-3 times daily. No transfer risk but requires frequent dosing
• Oral testosterone (Jatenzo) — Taken with food twice daily. Newer option with less liver concern than older oral formulations

Alternatives to TRT

For men with secondary hypogonadism, especially younger men concerned about fertility:

• Clomiphene citrate — An off-label use that stimulates the HPG axis to produce more testosterone naturally. Preserves fertility and testicular size. Not as effective as exogenous testosterone but avoids fertility complications.
• hCG (human chorionic gonadotropin) — Mimics LH, stimulating testicular testosterone production. Can be used alone or alongside TRT to maintain testicular function and fertility.
• Lifestyle optimization — Weight loss, exercise, sleep improvement, stress reduction, and addressing vitamin D deficiency can raise testosterone by 50-100+ ng/dL in some cases.

Monitoring on TRT

Once started, TRT requires ongoing monitoring:

First follow-up (6-8 weeks):

• Testosterone levels (trough — drawn just before next injection)
• Symptom assessment
• Side effect evaluation

Regular monitoring (every 6-12 months):

• Testosterone (total and free)
• Hematocrit/hemoglobin — TRT stimulates red blood cell production. Hematocrit above 54% requires dose reduction or blood donation
• PSA — monitor for changes, especially in men over 50
• Estradiol — elevated E2 can cause gynecomastia, mood changes, and water retention
• Lipid panel — TRT can affect HDL cholesterol
• Liver function (periodically)

What to watch for:

• Polycythemia (elevated red blood cells) — the most common clinically significant side effect
• Gynecomastia — breast tenderness or enlargement from testosterone conversion to estrogen
• Acne and oily skin
• Sleep apnea (TRT can worsen existing sleep apnea)
• Testicular atrophy (if not using hCG concurrently)
• Mood changes (irritability, aggression — uncommon at therapeutic doses)

Fertility Considerations

This is critical and often inadequately discussed: exogenous testosterone suppresses sperm production. TRT effectively functions as male contraception for most men. The suppression can be significant and in some cases irreversible.

If fertility is a concern:

• Consider clomiphene citrate or hCG instead of exogenous testosterone
• If TRT is necessary, concurrent hCG can maintain some spermatogenesis
• Discuss sperm banking before starting TRT if future fertility is important
• Don't assume fertility will return after stopping TRT — it usually does, but not always, and recovery can take 6-12 months or longer

Risks and Contraindications

Contraindications to TRT:

• Active prostate or breast cancer
• Hematocrit above 54% without identified cause
• Untreated severe obstructive sleep apnea
• Uncontrolled heart failure
• Desire for fertility without concurrent strategies to preserve it

Evolving evidence on cardiovascular risk:

The cardiovascular safety of TRT has been debated extensively. The TRAVERSE trial (published 2023) — the largest randomized controlled trial of TRT to date — found that testosterone therapy did not increase the risk of major adverse cardiovascular events in men with hypogonadism and pre-existing or high risk for cardiovascular disease. This was reassuring, though it doesn't mean TRT is cardioprotective.

The Bottom Line

TRT can be genuinely life-changing for men with legitimate hypogonadism. But it's a medical treatment, not a lifestyle upgrade — it requires proper diagnosis, appropriate monitoring, and an understanding of both benefits and risks.

If you're experiencing symptoms that might be related to low testosterone, the right first step is a proper evaluation — not ordering testosterone online or going to a clinic that will prescribe it to anyone with a credit card.

Start your evaluation at [coral.clinic/start](https://coral.clinic/start). Dr. Kim will order the right labs, interpret them in clinical context, and discuss whether TRT — or an alternative approach — makes sense for your situation.