TRT side effects. Facts and myths.

Testosterone replacement can change energy, mood, strength, and sex drive — but it also shifts blood, skin, fertility, and prostate health. Here is a clear, evidence-based guide to TRT side effects and how to manage them safely.

The relationship

Testosterone replacement therapy, or TRT, means using testosterone from outside the body to raise low levels back into a normal range. It is mainly used for men with hypogonadism, a condition where the testes or brain do not make enough testosterone for healthy sexual, physical, and mental function.^[1]

Meta analyses indicate that men with symptoms of low testosterone and total testosterone below about 350 ng/dL, or free testosterone below 100 pg/mL, are most likely to benefit from TRT.^[2] When these thresholds are used and men are properly screened, most studies show that TRT side effects are real but usually mild and manageable with the right dose and monitoring.^[1],[3]

TRT side effects tend to appear when blood testosterone climbs above a man’s personal “sweet spot” or when the drug form and schedule do not match his biology. Common issues include acne, fluid retention, a rise in red blood cell count, changes in fertility, breast tenderness, and shifts in cholesterol patterns.^[1],[4] Less commonly, TRT can unmask an underlying prostate cancer or worsen untreated sleep apnea.

How it works

To understand TRT side effects, it helps to see how external testosterone moves through the body and interacts with other hormones.

Testosterone delivery and blood levels

TRT can be given as injections, skin gels, patches, oral capsules, or long-acting pellets. Short-acting injections tend to produce sharp peaks and troughs in blood levels, while gels and longer-acting products produce flatter curves.^[3] Large swings can increase the chance of mood changes, acne, and high red blood cell counts compared with more stable regimens.

Guidelines from the American Urological Association recommend aiming for mid-normal testosterone levels for age and checking blood levels after starting or changing TRT, usually at 3 and 6 months, then at least yearly.^[1] In practice, using 350 ng/dL for total testosterone or 100 pg/mL for free testosterone as decision thresholds when symptoms persist helps separate under-treatment from overtreatment.

Conversion to estradiol and DHT

Estradiol is a form of estrogen made when the enzyme aromatase converts testosterone into estrogen. Dihydrotestosterone, or DHT, is a stronger form of testosterone produced by 5-alpha-reductase in tissues like the prostate and skin. Both estradiol and DHT rise when testosterone increases.^[2],[4]

Higher estradiol can cause breast tenderness, nipple sensitivity, and fluid retention, especially in men who gain fat on TRT, because fat tissue has more aromatase.^[4] Higher DHT can thicken the skin’s oil glands and stimulate hair follicles, which increases the risk of acne, oily skin, and male pattern hair loss in genetically prone men.

Effects on red blood cells and clotting

TRT stimulates the bone marrow, the spongy tissue inside bones that makes blood cells. Over time this can raise hemoglobin and hematocrit, which are measures of red blood cell concentration.^[5] This side effect, called erythrocytosis, is one of the most consistent TRT side effects seen in trials.

Guidelines suggest holding or lowering TRT if hematocrit exceeds 54 percent, because very thick blood may increase the risk of clotting, stroke, or heart attack, especially in men with other cardiovascular risk factors.^[1],[5] Checking blood counts before starting TRT and at least every 6 to 12 months after helps catch this early.

Impact on fertility and testicular function

The hypothalamus-pituitary-gonadal axis is the hormone loop that connects the brain to the testes. When outside testosterone rises, the brain senses enough hormone and reduces its own signals, mainly luteinizing hormone (LH) and follicle-stimulating hormone (FSH).^[6]

This feedback shuts down sperm production and can shrink the testes over time, which is why TRT is usually not appropriate for men who want to preserve fertility. Alternatives like enclomiphene, a selective estrogen receptor modulator that boosts the body’s own testosterone production, can raise testosterone while keeping sperm-making signals active in some men with secondary hypogonadism.^[6]

Cardiometabolic effects

TRT can change cholesterol, blood pressure, and blood sugar. Some trials show modest drops in fat mass and increases in lean muscle, which may improve insulin sensitivity and waist size.^[3] At the same time, TRT can lower HDL cholesterol, the “good” cholesterol, and raise hematocrit, so overall heart risk depends on the individual man’s baseline health.

Large meta-analyses of randomized controlled trials find no major increase in short-term cardiovascular events when TRT is prescribed to screened men with clear hypogonadism, but they also stress the need for ongoing monitoring and caution in men with recent heart attack or stroke.^[3]

Conditions linked to it

Some TRT side effects are temporary annoyances. Others connect to deeper conditions that matter for long-term health.

• Erythrocytosis and blood clots: As noted, TRT commonly raises hematocrit. When levels pass about 54 percent, risk of blood clots, stroke, and heart attack may rise, especially in older men and those with smoking, obesity, or prior clotting issues.^[5]
• Fertility problems: Continuous TRT can sharply lower sperm counts, sometimes to zero. This can lead to temporary or, in some cases, long-lasting infertility, particularly when high doses are used for years.^[6]
• Prostate growth and cancer detection: TRT usually causes a small rise in prostate-specific antigen (PSA), a marker released by prostate cells, and may speed up growth of benign prostate enlargement. Current evidence does not show that TRT causes prostate cancer, but it can unmask an existing tumor by accelerating PSA changes.^[1],[7]
• Sleep apnea worsening: In men with untreated obstructive sleep apnea, TRT may worsen breathing pauses at night, likely by altering respiratory drive and upper airway tone.^[4]
• Metabolic shifts: TRT can slightly lower HDL cholesterol and raise triglycerides in some men, while improving fat mass and insulin sensitivity in others, so net metabolic impact varies person to person.

Limitations note: Much of the long-term data on TRT and major events like heart attack, stroke, or prostate cancer comes from observational studies with mixed results. Ongoing trials are still clarifying risks over 5 to 10 years and beyond.

Symptoms and signals

Not every change on TRT is dangerous. The key is learning which TRT side effects are “yellow flags” that need adjustment and which may signal a more serious issue.

• Skin and hair changes
  • New or worse acne on face, back, or chest
  • Oily skin or increased sweating
  • Faster beard growth
  • Thinning hair at the temples or crown if you are already prone to male pattern baldness
• Fluid and breast changes
  • Swollen ankles or sudden weight gain from fluid
  • Fullness, tenderness, or a rubbery lump under one or both nipples
  • Feeling puffy, especially around the face or hands
• Blood and circulation clues
  • New headaches, especially if throbbing or worse after exertion
  • Flushing or a ruddy, dark-red face
  • Shortness of breath or chest discomfort with mild activity
  • Leg swelling or pain, which can signal a blood clot and needs urgent care
• Sexual and reproductive shifts
  • Improved sex drive and erections, which are expected
  • Lower semen volume or “dry” orgasms
  • Noticeable shrinkage of the testicles over months
  • Difficulty conceiving with a partner after starting TRT
• Mood and energy changes
  • Better motivation, focus, and mood within weeks is common
  • But also watch for irritability, feeling “amped up,” or trouble sleeping
  • On fluctuating injections, a “roller coaster” pattern of high-energy days followed by crashes
• Prostate and urinary signs
  • More frequent urination, especially at night
  • Weaker stream or straining to start
  • Burning, blood in urine, or sudden inability to pass urine, which needs urgent evaluation
• Sleep and breathing
  • Louder snoring reported by a bed partner
  • Waking up choking, gasping, or with morning headaches
  • Feeling unrefreshed despite enough hours in bed

What to do about it

Most TRT side effects can be prevented or controlled with the right plan. Here is a simple roadmap.

1. Step 1: Get properly tested before starting
   • Confirm symptoms of low testosterone such as low sex drive, erectile issues, low energy, depressed mood, or loss of muscle.
   • Check morning total testosterone on at least two separate days, and free testosterone if levels are borderline.
   • Screen for other causes of symptoms: thyroid problems, depression, medications, heavy alcohol use, and sleep apnea.
   • Baseline labs should include blood counts, PSA, liver function, fasting lipids, and sometimes an A1c for blood sugar.
2. Step 2: Choose the right tool for your goals
   • Discuss TRT forms: injections, gels, patches, pellets, or oral agents. Each differs in convenience, cost, and side-effect profile.
   • If fertility matters, ask about alternatives like enclomiphene or hCG-based protocols that support sperm production rather than replacing testosterone outright.
   • Start with the lowest effective dose that brings testosterone into the mid-normal range and improves symptoms, instead of targeting “bodybuilder” levels.
3. Step 3: Monitor and adjust over time
   • Recheck testosterone, blood counts, and PSA at 3 and 6 months, then at least once a year.
   • Track blood pressure, waist size, weight, and lipid profile, since TRT side effects can show up in the heart and metabolism as much as in the mirror.
   • Report any red flag symptoms promptly: chest pain, breathing trouble, severe headaches, leg swelling, or urinary blockage.
   • Be ready to adjust dose, switch formulations, or pause TRT if labs cross unsafe thresholds.

Myth vs Fact: Clearing the air on TRT side effects

• Myth: “TRT always causes prostate cancer.”
  Fact: Current evidence shows TRT does not create new prostate cancer in screened men, though it can speed PSA changes if a cancer is already present, which is why PSA monitoring is mandatory.^[1],[7]
• Myth: “Once you start TRT, you can never stop.”
  Fact: Many men can taper off TRT under medical supervision, though they may feel a dip in energy and libido while the body restarts its own production. Long-term, very high-dose use makes this harder, which is another reason to avoid supraphysiologic dosing.^[6]
• Myth: “TRT is just legal steroids, so side effects are the same as bodybuilding cycles.”
  Fact: Medically supervised TRT aims for normal levels, not massive surges. The side-effect profile at physiologic doses is far milder than with anabolic steroid abuse, though shared risks like erythrocytosis and fertility suppression still exist.^[5]
• Myth: “If you feel good on TRT, lab monitoring is optional.”
  Fact: Some of the most serious TRT side effects, like rising hematocrit or PSA, are silent at first. You cannot “feel” them until they cause trouble, so labs are non-negotiable even when you feel great.^[1],[5]
• Myth: “Higher testosterone automatically means better results.”
  Fact: Studies show benefits plateau once testosterone reaches a mid-normal range, while side effects keep climbing at higher doses. More is not better; right is better.^[2],[3]

Bottom line

TRT side effects are not a reason to avoid treatment when real hypogonadism is hurting your quality of life. They are a reason to slow down, get the right testing, and work with a clinician who treats testosterone like the powerful hormone it is, not a wellness fad. The safest path is simple: confirm the diagnosis, choose the gentlest tool that fits your goals, and use scheduled labs and honest symptom tracking to fine-tune over time. With that framework in place, most men can gain the upsides of TRT while keeping the downsides on a tight leash.

References

1. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. The Journal of urology. 2018;200:423-432. PMID: 29601923
2. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. The Journal of clinical endocrinology and metabolism. 2018;103:1715-1744. PMID: 29562364
3. Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert opinion on drug safety. 2014;13:1327-51. PMID: 25139126
4. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. European urology. 2009;55:310-20. PMID: 18838208
5. Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. The journals of gerontology. Series A, Biological sciences and medical sciences. 2005;60:1451-7. PMID: 16339333
6. Patel AS, Leong JY, Ramos L, et al. Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility. The world journal of men’s health. 2019;37:45-54. PMID: 30350483
7. Khera M, Morgentaler A. Reply to Julia Klap and Kevin R. Loughlin’s letter to the editor re: Mohit Khera, David Crawford, Alvaro Morales, Andrea Salonia, Abraham Morgentaler. A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol 2014;65:115-23. European urology. 2014;66:e33. PMID: 24836155