Facing the truth: My experience with testosterone replacement therapy side effects

Testosterone replacement can restore energy, muscle, and sex drive, but it also changes how your whole system works. Here is a clear, evidence-based guide to testosterone replacement therapy side effects and how to manage them safely.

The relationship

Testosterone is the main male sex hormone. It helps control muscle mass, bone strength, red blood cell production, mood, and sex drive. When levels drop too low, men can feel exhausted, weaker in the gym, and less like themselves.

Testosterone replacement therapy, or TRT, means giving testosterone from outside the body through injections, gels, patches, pellets, or oral capsules to bring blood levels back into the normal range. Meta-analyses suggest that symptomatic men with total testosterone below 350 ng/dL, or free testosterone below 100 pg/mL, are most likely to benefit from TRT when other causes of symptoms are ruled out.^[1]

The same hormone that improves energy and performance can also cause problems when the dose is too high, the wrong men are treated, or monitoring is poor. Large reviews and guidelines from the American Urological Association and European Association of Urology show that most testosterone replacement therapy side effects are predictable and manageable when therapy is supervised carefully, but risks increase when monitoring is ignored.^[1],[2]

How it works

To understand testosterone replacement therapy side effects, it helps to know how TRT changes your internal “control panel.” The main issues come from how testosterone affects blood, fluid balance, hair follicles, and the way your brain controls hormone production.

Testosterone and red blood cell production

Erythropoiesis means red blood cell production in the bone marrow. Testosterone acts on the kidneys to increase erythropoietin, a hormone that tells the marrow to make more red blood cells. This can raise hemoglobin and hematocrit, the lab values that show how concentrated your blood is.^[3]

Clinical trials show that up to 18–20% of men on TRT develop elevated hematocrit above 54%, a level where blood becomes thicker and the risk of clotting and cardiovascular events may rise, especially in older men and those with sleep apnea or prior clots.^[3]

Fluid retention and blood pressure

TRT can increase sodium and water reabsorption in the kidneys. Reabsorption means pulling fluid back into the bloodstream instead of letting it leave the body as urine. This can lead to mild fluid retention, ankle swelling, and small rises in blood pressure in some men.

Most studies show average blood pressure changes are small, but men with heart failure, uncontrolled hypertension, or kidney disease are more likely to feel this side effect and may need closer monitoring or a lower dose.^[2]

Skin, oil glands, and hair follicles

When testosterone enters certain tissues, an enzyme called 5-alpha-reductase converts part of it into dihydrotestosterone, or DHT. DHT is a stronger form of testosterone that acts powerfully on hair follicles and oil glands in the skin.

Higher DHT levels can lead to acne, oily skin, and faster male pattern baldness in men who are genetically prone. Studies suggest that acne or oily skin occurs in about 5–15% of men on TRT, and hair loss often speeds up in men who were already thinning.

Hormone feedback loop and fertility

The hypothalamic–pituitary–gonadal axis is the hormone feedback loop connecting your brain and testes. When you take external testosterone, your brain senses higher levels and turns down luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These two pituitary hormones tell the testes to make both testosterone and sperm.

Shutting down LH and FSH can shrink testicular size and reduce or stop sperm production. Controlled trials show that TRT can lower sperm counts to near zero in many men within 3–6 months, which is why major guidelines advise against TRT as a treatment in men who want to preserve fertility.^[1]

Testosterone, mood, and sleep

Testosterone receptors sit throughout the brain, including areas that control mood, drive, and sleep. Receptor means a docking site where a hormone can attach and send a signal. In men with clear deficiency, TRT often improves fatigue, depressive symptoms, and sexual desire, but rapid dose changes can sometimes trigger irritability, mood swings, or restlessness.^[4]

TRT can also worsen untreated obstructive sleep apnea, a condition where the airway collapses during sleep. Men with severe snoring and daytime sleepiness should be screened before and during therapy because low oxygen at night plus thicker blood is a risky combination.^,[4]

Conditions linked to it

Testosterone replacement therapy side effects cluster into a few key medical issues. Not every man will face these, but they deserve attention before you start.

• Thickened blood (erythrocytosis) – Elevated hematocrit above 54% can increase clot risk. Men with a history of blood clots, stroke, or uncontrolled sleep apnea have a higher baseline risk and should be monitored more often or may be poor candidates for TRT.^[3]
• Cardiovascular events – Research is mixed. Some observational studies suggest increased risk of heart attack and stroke in older men with multiple risk factors, while more recent randomized trials and meta-analyses show neutral or even modestly beneficial effects on cardiovascular outcomes when TRT is used appropriately in hypogonadal men.^[2]
• Prostate enlargement and urinary symptoms – Testosterone can worsen lower urinary tract symptoms in men with existing benign prostatic hyperplasia, or BPH, which is non-cancerous prostate enlargement. Current evidence does not show that TRT causes prostate cancer, but it may unmask cancer that was already there by speeding PSA rises.^[2]
• Gynecomastia – This means breast tissue growth in men. Some testosterone is converted to estrogen by an enzyme called aromatase, especially in body fat. If this balance shifts too far, men can notice tender or swollen breast tissue.
• Infertility – As noted, TRT commonly suppresses sperm production. For men hoping to have children, this is one of the most serious potential complications and may take months to reverse after stopping therapy, if it reverses fully at all.

Limitations note: Most safety data come from studies lasting 1–3 years, often in selected groups such as older men with clear hypogonadism. Long-term outcomes over decades, and risks in younger men using higher doses or non-prescribed products, are less certain.

Symptoms and signals

Knowing what to watch for can help you spot testosterone replacement therapy side effects early. Bring these up with your clinician rather than trying to tweak your dose on your own.

• New or worsening headaches, vision changes, or a flushed face that feels different from your usual workouts
• Shortness of breath, chest pain, sudden leg swelling, or calf pain, which may signal a blood clot
• Rapid weight gain over a few days, puffy ankles or fingers, or feeling uncomfortably “full of water”
• Acne on the back, chest, or shoulders that is new or clearly worse than before TRT
• Faster scalp hair thinning in men already prone to male pattern baldness
• Breast tenderness, nipple sensitivity, or a firm lump under one or both nipples
• Increased nighttime urination, weaker urine stream, or a feeling that you cannot fully empty your bladder
• Snoring that gets louder, witnessed apneas where you stop breathing at night, or waking up unrefreshed despite enough hours in bed
• Mood swings, unusual irritability, or feeling “amped up” and restless when your dose increases
• Drop in ejaculate volume, changes in testicular size, or trouble conceiving with a partner after starting TRT

Lab signals your clinician will watch for include:

• Hematocrit climbing above 50%, and especially above 54%
• PSA rising more than 1.4 ng/mL in a year or above age-specific normal ranges
• Significant jumps in blood pressure compared to your baseline
• Testosterone levels consistently above the upper normal range for healthy young men

What to do about it

A structured plan can help you get the benefits of TRT while reducing the risk of testosterone replacement therapy side effects.

1. Get tested and confirm the diagnosis
   Ask for at least two early-morning total testosterone tests on different days, plus free testosterone if the total is borderline. If you are below 350 ng/dL with clear symptoms, or free testosterone is below 100 pg/mL, talk with your clinician about TRT versus other causes such as poor sleep, heavy drinking, certain medications, or untreated depression.^[1]
2. Use lifestyle plus the lowest effective dose
   Start with evidence-based lifestyle moves that can raise or support testosterone: 7–9 hours of quality sleep, resistance training 2–4 days per week, reducing excess body fat, moderating alcohol, and managing stress. For some men, natural ways to increase testosterone may be enough to improve symptoms or delay the need for TRT. If you and your clinician decide TRT is right, begin with a conservative dose that targets mid-normal levels, not bodybuilder ranges, and choose a delivery method you can stick with, such as weekly or biweekly injections or daily gel.^[4]
3. Monitor, adjust, and protect your long-term health
   Plan lab checks at 3 months, 6 months, and then at least yearly, including testosterone level, hematocrit, PSA, and a basic metabolic panel. Add sleep apnea screening if you snore loudly or feel exhausted in the morning. Report side effects early; small dose adjustments, changing injection frequency, or switching to another form can often solve problems without stopping therapy entirely.^[2]

Myth vs Fact: Testosterone replacement therapy side effects

• Myth: “TRT always causes prostate cancer.”
  Fact: Current evidence does not show that TRT causes prostate cancer, but it can speed PSA changes and reveal cancers that were already present, so regular screening is essential.^[2]
• Myth: “If I feel great, higher doses are always better.”
  Fact: Doses above the normal physiological range raise side effect risks sharply, including thickened blood, acne, mood swings, and fertility loss, without proven long-term benefits.^[3]
• Myth: “TRT will fix my sex life no matter what.”
  Fact: Testosterone can improve desire in men with true deficiency, but erection issues often also involve blood vessel health, nerve function, and relationship factors. Sometimes addressing erectile dysfunction causes, counseling, or lifestyle changes are still needed.^[4]
• Myth: “Natural or underground testosterone is safer than prescription TRT.”
  Fact: Non-prescribed products often contain unknown doses, contaminants, or other steroids. They bypass medical monitoring, which is the key safety net for catching side effects early.
• Myth: “TRT is off-limits if you care about your heart.”
  Fact: For men with clear hypogonadism, several recent trials show neutral or even improved cardiovascular markers with properly dosed TRT, though men with recent heart attack or stroke still need careful, individualized decisions.

Bottom line

Testosterone replacement therapy can be life-changing for men with true hormone deficiency, but it is not a zero-risk upgrade. Most testosterone side effects come from predictable shifts in blood thickness, fluid balance, skin oil production, prostate activity, and the brain–testes feedback loop. The goal is not chasing the highest number on a lab report; it is hitting steady, mid-normal levels while protecting your heart, blood, prostate, and fertility. If you partner with a clinician, stay honest about your goals, and respect the follow-up plan, TRT can be a powerful tool instead of a long-term problem.

References

1. 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
2. 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
3. Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. The Journal of clinical endocrinology and metabolism. 2008;93:914-9. PMID: 18160461
4. Corona G, Isidori AM, Buvat J, et al. Testosterone supplementation and sexual function: a meta-analysis study. The journal of sexual medicine. 2014;11:1577-92. PMID: 24697970