Testosterone replacement therapy or TRT has garnered relatively fast attention via social media and online advertisements. It’s almost impossible to miss the countess ads in your streams on platforms like X or Facebook. The curious question is what’s driving this interest and are the results being promised real or too good to be true? Let’s take a look back before we go forward.
By the end of the 1980’s the image of the masculine man with huge muscles and overly tanned skin began to lose favor as less people found it attractive or desirable to look that way. As its leading examples in Hollywood started to age and their careers started to wane, the look also lost interest. Then in 1990 the congress passed “The Anabolic Steroid Control Act” making testosterone and its derivatives class 3 controlled substances. This means doctors would be extremely limited in who they could prescribe to, must get a DEA license to prescribe and the dosing would be tracked to prevent fraudulent use. This unfortunately led to a black market with often questionable products.
Fast forward to the 2000’s with X-Men and particularly 2008 when the Marvel Cinematic Universe began, we started to see muscular heroes on screen again. And not just in superhero movies, but also in Barbie, Creed, Roadhouse and many others. We’ve all seen the transformation that the stars went through, and suddenly ripped muscles have become cool again. There is an entire bro culture based around this. If you watch NFL football, it’s hard not to notice the number of jacked referees these days. It’s a new gun show. The idea of muscularity defining masculinity is upon us once again, perhaps not to the extremes of the 80’s, but the idea of optimizing oneself is the here and now.
Testosterone Replacement Therapy (TRT)
Testosterone is more than just the “male hormone.” It’s a key driver of muscle mass, bone density, libido, mood, and overall vitality. When levels drop below normal, the effects can ripple through nearly every system in the body. For some men TRT can be life changing. For others, it may not be the right fit—or at least not the first step
Recognizing the Symptoms of Low Testosterone
Low testosterone (often called “low T” or hypogonadism) can develop gradually, making it easy to dismiss symptoms as “just getting older.” But when multiple signs cluster together, it’s worth investigating.
Common symptoms include:
Sexual changes: Reduced libido, erectile dysfunction, lower semen volume, infertility
Physical changes: Loss of muscle mass and strength, increased body fat (especially abdominal), decreased bone density, hot flashes
Energy and recovery: Persistent fatigue, slower recovery from exercise or injury
Mood and cognition: Irritability, low mood, brain fog, reduced motivation
Other signs: Sleep disturbances, anemia, smaller testicular size
A diagnosis requires both symptoms and low morning testosterone levels on at least two separate blood tests.
Types of TRT: Delivery Methods and Trade-offs
TRT isn’t one-size-fits-all. The delivery method can influence hormone stability, side effects, convenience, and cost.
Types of Testosterone Replacement Therapy (TRT)
1. Injectable Testosterone – Includes forms like testosterone cypionate, enanthate, propionate, and undecanoate. These are given via intramuscular or subcutaneous injection, with dosing intervals ranging from weekly to every several weeks depending on the ester type. They allow precise dosing but can cause hormone peaks and troughs that affect mood, blood pressure, or energy. Studies show more frequent micro doses can reduce negative side effects.
2. Transdermal Gels and Creams – Examples include AndroGel, Testim, Fortesta, and Axiron. Applied daily to the skin, they provide steady absorption and are easy to adjust, but absorption can vary between individuals and there’s a risk of transferring the medication to others through skin contact.
3. Skin Patches – Such as Androderm. These are applied once daily and deliver testosterone consistently but can cause skin irritation or adhesion problems for some users.
4. Nasal Gel – Natesto is the main example. It’s applied inside the nostrils three times a day, avoids skin transfer, and absorbs quickly, but requires frequent dosing and may cause nasal irritation. Contraindicated for those with frequent sinus issues.
5. Buccal Tablets – Placed against the upper gum twice daily, these bypass liver metabolism and provide steady delivery but can cause gum irritation or an unpleasant taste.
6. Oral Capsules – Testosterone undecanoate in capsule form (such as Kyzatrex or Jatenzo) is absorbed through the lymphatic system. It’s convenient and needle-free, but absorption depends on taking it with a fat-containing meal. Studies show it’s less likely to increase hematocrit and blood pressure. Because of its short half life natural testosterone production is not totally shut down.
7. Subcutaneous Pellets – Testopel is the most common brand. Small pellets are implanted under the skin every three to six months, providing long-term delivery without daily dosing. However, the procedure is minor surgery, and adjusting the dose once implanted is difficult. Also, for men the size of the pellets is a quite large V-shaped risen area on the hip.
Choosing the right form depends on your symptom profile, lab trends, cardiovascular risk, and lifestyle.
Alternatives to TRT
If your testosterone is borderline low or if fertility preservation is a priority there are options that stimulate your body’s own production rather than replacing testosterone outright.
Medical alternatives:
Clomiphene citrate (Clomid): Stimulates the brain to produce more LH/FSH, boosting natural testosterone; preserves fertility.
Enclomiphene: A purified isomer of Clomid with fewer side effects.
hCG (human chorionic gonadotropin): Mimics LH to stimulate the testes directly; often used alongside TRT to maintain fertility.
Lifestyle and nutritional strategies:
Resistance training and high-intensity interval training (HIIT)
Adequate sleep (7–9 hours)
Weight loss (especially reducing visceral fat)
Correcting deficiencies in vitamin D, zinc, and magnesium
Stress reduction techniques (breathwork, meditation)
These approaches can be used alone in mild cases or alongside TRT to optimize results.
Potential Risks of TRT
While TRT can restore vitality, it’s not without risks, especially if not closely monitored.
Cardiovascular and hematologic:
Polycythemia (elevated red blood cell count), increasing clot risk
Possible BP elevation
Mixed evidence on heart attack and stroke risk (see TRAVERSE Study below)
Hormonal and reproductive:
Testicular shrinkage
Infertility (suppresses sperm production)
Gynecomastia (breast tissue growth)
Other:
Acne, oily skin
Worsening of sleep apnea
Prostate enlargement (BPH) and the need for cancer screening
Legal note: In the U.S., testosterone is a Schedule III controlled substance. It requires a prescription, has refill limits, and improper prescribing or possession can carry legal consequences.
The TRAVERSE Study: What We Learned About TRT and Heart Health
For years, one of the biggest questions about TRT was whether it increased the risk of heart attack, stroke, or death in men with cardiovascular risk factors. The TRAVERSE Study, published in 2023, provided the most definitive answer yet.
Study design:
5,246 men aged 45–80 with low testosterone (
Randomized to daily testosterone gel or placebo
Followed for ~33 months
Key findings:
No increase in major cardiovascular events (heart attack, stroke, cardiovascular death) in the TRT group compared to placebo
However, TRT users had higher rates of:
Nonfatal arrhythmias (including atrial fibrillation)
Pulmonary embolism
Acute kidney injury
Slightly higher fracture risk
Takeaway: TRT appears safe from a major cardiovascular event standpoint in properly diagnosed men, but vigilance is needed for clotting and rhythm issues—especially in older or high-risk patients.
Risk-Benefit Considerations of TRT by Age
The decision to start TRT looks different at 28 than it does at 68.
Under 30:
Often secondary hypogonadism or lifestyle-related
Fertility preservation is critical—TRT can suppress sperm production
Alternatives like Clomid or hCG are often preferred first
Ages 30–45:
Natural decline begins (~1% per year after 30)
Lifestyle optimization can still reverse mild low T
TRT considered if symptoms are significant and confirmed by labs
Ages 45–60:
Age-related hypogonadism is more common
TRT can help preserve bone density, muscle mass, and libido
Requires regular monitoring of hematocrit, PSA, BP, and lipids
Over 60:
Higher baseline cardiovascular and prostate risks
Careful screening for sleep apnea, heart failure, and cancer is essential
Decision often balances quality of life vs. longevity concerns
Testosterone and Mood: The Depression Connection
Low testosterone doesn’t just sap physical energy—it can erode mental well-being. Research has linked low T to depressive symptoms, irritability, and reduced motivation.
What the studies say:
A meta-analysis in the Journal of Psychiatric Practice found TRT significantly reduced depressive symptoms in men with low T, especially those with mild-to-moderate depression.
An American Journal of Psychiatry study showed older men with dysthymia improved more on TRT than placebo.
Benefits appear strongest in men with both low T and depressive symptoms—not in men with normal levels.
Possible mechanisms:
Testosterone modulates serotonin and dopamine pathways
It may enhance neuroplasticity and hippocampal volume
It can reduce cortisol’s negative effects on mood
Caveat: TRT is not a first-line treatment for depression unless low T is confirmed. Antidepressants, therapy, and lifestyle changes remain core treatments.
The Bottom Line
TRT can be a powerful tool for men with confirmed low testosterone and significant symptoms. It can restore energy, muscle mass, libido, and even improve mood. But it’s not a magic bullet—and it’s not without risks.
Key takeaways:
Always confirm low T with symptoms and labs before starting
Choose a delivery method that fits your physiology and lifestyle
Monitor hematocrit, PSA, BP, and cardiovascular status regularly
Consider alternatives first if you’re young or want to preserve fertility
Use the TRAVERSE Study as a framework: major CV events aren’t increased, but clotting and arrhythmia risks require vigilance
Mood benefits are real for men with low T, but TRT is not a universal antidepressant
Final thought: The best TRT plan is personalized—tailored to your age, health status, goals, and risk profile, with ongoing adjustments based on data. If you’re considering TRT find a medical provider who will track your labs, symptoms, and side effects.
Some individuals will be lured to the prospects of bigger muscles and greater strength associated with testosterone. While this appeal may be understandable it also comes with significant risks. Using testosterone or its derivatives will shut down natural production and render you infertile. While in many cases this is reversable overtime, in some cases it’s not. It also can increase risks associated with medical conditions you are or aren’t aware of. Be honest with your doctor, take regular blood tests and keep to the prescribed dose. Taking higher doses (more common with injectables) significantly increases the risks. Taking doses 2+ times, the amount prescribed is basically taking steroids (gear) and the negative side effects are just as real.
References:
Long Term Cardiovascular Safety of Testosterone Therapy: A Review of the TRAVERSE Study https://pmc.ncbi.nlm.nih.gov/articles/PMC11937349/
https://www.uspharmacist.com/article/a-review-of-testosterone-therapy-options-for-men
Testosterone therapy: Potential benefits and risks as you age https://www.mayoclinic.org/healthy-lifestyle/sexual-health/in-depth/testosterone-therapy/art-20045728
TRT Dosing And Frequency Breakdown With Dr. Peter Attia https://www.youtube.com/watch?v=RtpCh6U9v6o