TRT Side Effects: An Honest Look

If you're considering testosterone replacement therapy, you've probably seen scary headlines about heart attacks, strokes, and prostate cancer. You've also probably seen marketing that makes TRT sound like a risk-free fountain of youth. The truth is somewhere in between—and understanding the real risks helps you make an informed decision.

Let's break down what the research actually shows, separating common side effects from rare ones, and debunked concerns from legitimate ones worth monitoring.

Common Side Effects (And How They're Managed)

These are the side effects that affect a meaningful percentage of men on TRT. None of them are dangerous when properly monitored, but they do require attention.

Polycythemia (Elevated Red Blood Cell Count)

This is the most common side effect of TRT, affecting over 20% of men on treatment. Testosterone stimulates red blood cell production—which is actually beneficial if you're anemic, but problematic if it goes too high.

The concern with polycythemia is that thicker blood could theoretically increase risk of blood clots, stroke, or heart attack. While this theoretical risk hasn't been demonstrated in clinical trials, it's still taken seriously.

How it's managed: Your hematocrit (percentage of red blood cells in your blood) is monitored regularly. If it rises above 52-54%, treatment is typically paused until levels normalize. Some men require periodic therapeutic phlebotomy (blood donation) to keep levels in check. The delivery method matters too—intramuscular injections cause the biggest hematocrit increases (around 4%), while gels and nasal preparations cause smaller increases.

Acne and Oily Skin

Testosterone increases sebum production, which can lead to acne—especially in men who were acne-prone as teenagers. This is more common with injections (which cause testosterone spikes) than with gels (which provide steadier levels).

How it's managed: Usually responds to standard acne treatments. Switching to a gel formulation can help if injections are causing problems.

Testicular Shrinkage and Reduced Sperm Production

When you take external testosterone, your body's natural production shuts down. The pituitary gland stops sending signals to the testicles, causing them to shrink (typically about 25% smaller) and produce less sperm.

For men not concerned about fertility, this is mostly a cosmetic issue. For men who want to preserve fertility, it's a significant consideration.

How it's managed: Human chorionic gonadotropin (hCG) can be prescribed alongside TRT to maintain testicular function and sperm production. Alternatively, some men use clomiphene citrate instead of TRT, which raises testosterone while preserving fertility. If fertility preservation matters to you, discuss this before starting treatment.

Gynecomastia (Breast Tissue Growth)

Testosterone can convert to estrogen through a process called aromatization. If estrogen levels get too high relative to testosterone, some men develop breast tenderness or breast tissue growth.

How it's managed: Estrogen levels are monitored alongside testosterone. If gynecomastia develops, aromatase inhibitors (like anastrozole) can reduce estrogen conversion. Tamoxifen is sometimes used to block estrogen's effects on breast tissue directly.

Sleep Apnea Worsening

TRT can worsen obstructive sleep apnea in men who already have it, or potentially unmask mild cases. The mechanism isn't fully understood but may involve changes to upper airway muscles or central respiratory drive.

How it's managed: Men with known sleep apnea should have it treated (usually with CPAP) before starting TRT. If you develop snoring or daytime sleepiness on TRT, a sleep study may be warranted.

Fluid Retention and Edema

Some men experience ankle swelling or general fluid retention on TRT. This is usually mild but can be problematic for men with heart failure or kidney issues.

How it's managed: Usually resolves with dose adjustment. Men with significant heart or kidney disease need closer monitoring.

The Cardiovascular Question: Largely Resolved

For years, cardiovascular risk was the biggest concern around TRT. Some early observational studies suggested increased heart attack and stroke risk, leading the FDA to issue warnings in 2015.

Then came the TRAVERSE trial, published in the New England Journal of Medicine in 2023. This was a massive, randomized, placebo-controlled trial of 5,246 men aged 45-80 who already had cardiovascular disease or high risk factors. The results were clear: TRT was "noninferior to placebo"—meaning it didn't increase the incidence of heart attacks, strokes, or cardiovascular death.

Based on this evidence, the FDA removed its cardiovascular warning from testosterone products in February 2025. This doesn't mean TRT is completely risk-free for the heart—men with existing cardiovascular disease should still be monitored closely—but the feared increased risk hasn't materialized in rigorous trials.

The Prostate Question: Also Reassuring

There's been long-standing concern that testosterone might stimulate prostate cancer growth, based on the observation that prostate cancer often responds to androgen deprivation therapy.

However, research hasn't supported the fear that TRT increases prostate cancer risk in men without existing cancer. Multiple studies have found no significant increase in prostate cancer diagnosis rates in men on TRT. PSA levels do often increase modestly, which is why monitoring is important, but this doesn't translate to increased cancer rates.

That said, TRT is contraindicated in men with untreated prostate cancer or breast cancer. If you have a history of these cancers, TRT requires careful discussion with an oncologist.

Less Common Side Effects

These affect a smaller percentage of men but are worth knowing about:

• Mood changes: Some men report irritability or mood swings, especially with injection formulations that cause testosterone peaks and valleys. Switching to gels or more frequent injections often helps.
• Hair loss: If you're genetically predisposed to male pattern baldness, TRT may accelerate it. Testosterone converts to DHT, the hormone primarily responsible for hair loss.
• Skin reactions: Transdermal gels and patches can cause application site reactions in some men.
• Blood pressure elevation: Some men experience modest blood pressure increases that require monitoring.
• Liver concerns: Oral testosterone formulations (less commonly used) can stress the liver. Injectable and transdermal formulations don't have this issue.

Who Should Be Cautious

While TRT is safe for most men with genuine testosterone deficiency, certain conditions warrant extra caution or may be contraindications:

Minimizing Side Effects: Practical Tips

Based on the research and clinical practice, here's how to reduce your risk of side effects:

1. Start with appropriate testing: Make sure you actually have low testosterone (confirmed by two morning blood tests) before starting treatment. Don't treat normal levels.
2. Choose the right delivery method: Gels and nasal preparations cause smaller hematocrit increases than injections. If you have polycythemia concerns, this matters.
3. Maintain proper monitoring: Don't skip blood work. Catching elevated hematocrit or estrogen early prevents bigger problems.
4. Target the right testosterone level: More isn't better. Aim for the normal range (typically 350-750 ng/dL), not supraphysiological levels.
5. Address underlying health: Sleep apnea, obesity, and metabolic issues should be addressed regardless of TRT.

The Bottom Line

TRT is a well-established treatment with decades of clinical use. The side effects are real but manageable with proper monitoring. The cardiovascular and prostate cancer fears that dominated headlines for years haven't been borne out by rigorous research.

The key is working with a provider who takes monitoring seriously. Cheap TRT clinics that skimp on blood work aren't worth the risk. Quality telehealth platforms include comprehensive testing as part of their protocols—that's what you should expect.

If you have genuine testosterone deficiency with symptoms affecting your quality of life, TRT can be genuinely life-changing. Just go in informed, follow monitoring protocols, and communicate with your provider about any changes you notice.