Testosterone Therapy: What the Evidence Actually Shows

Testosterone therapy carried class-wide cardiovascular warning language for years. After the 5,246-man TRAVERSE randomized trial found no increase in its primary major cardiovascular endpoint, FDA removed the cardiovascular boxed-warning language from testosterone products on February 28, 2025. FDA also added class-wide blood-pressure information. [1,2]

In June 2026, FDA/HHS requested additional label updates, including removal of the prior age-related hypogonadism limitation of use. [3]

The conversation should change when the evidence and the FDA labeling change. That is exactly how our Testosterone Therapy evaluations now begin — with the current labeling and the individual risk picture, not the old blanket warnings.

Testosterone receptors are found throughout the body. Testosterone affects far more than libido.

This is why a testosterone evaluation at Better Off starts with the whole endocrine and metabolic picture — the same framework as our Hormone Optimization program — rather than a single symptom or a single lab number.

Testosterone is one part of the body-composition conversation — protein intake, resistance training, sleep and metabolic health belong in the same assessment. See our Body Composition & Muscle Loss care path.

Testosterone and estradiol act through receptors distributed throughout the body — not only in reproductive tissues.

Muscle, bone, brain, vascular tissue, fat, skin and other organs respond to androgen and estrogen signaling. [8] This helps explain why low testosterone can present as a cluster of seemingly unrelated problems instead of one isolated symptom.

It also means our understanding of sex-hormone biology is still evolving — the same emerging-receptor framework we describe on our women's hormone therapy evidence page.

A portion of testosterone converts to estradiol through the aromatase enzyme.

Estradiol is not simply an unwanted by-product. Men need estrogen too. It contributes to sexual function, bone, body-composition physiology and other estrogen-responsive tissues. [8,9]

The goal is not to drive estradiol as low as possible. The goal is to recognize when the level and the symptoms suggest too much or too little estrogen.

What Better Off's earlier male-estradiol handout teaches

If estrogen is running high, the first approach may be DIM (di-indolyl-methane), derived from cruciferous vegetables. The original Better Off patient handout uses 300 mg DIM daily for men as a typical clinic approach.

If DIM does not adequately control conversion, an aromatase inhibitor such as anastrozole (Arimidex) may be prescribed. The original handout describes 0.5 mg twice weekly as a typical clinic regimen and makes an important point:

More is NOT better.

If estradiol becomes too low, men may develop irritability/anger, headaches and erectile dysfunction. Holding doses can allow estradiol to recover.

A practical clue patients can recognize

If morning erections disappear or erectile function changes, look for symptoms of both high and low estradiol rather than assuming testosterone alone is the problem.

This section incorporates the earlier Better Off patient handout “For men receiving testosterone replacement therapy” and preserves its symptom list and clinic-management approach.

A number on a lab report is not self-interpreting.

Subcutaneous pellets release testosterone over months rather than producing a perfectly flat level.

A lab drawn near the post-insertion peak and a lab drawn near the pre-insertion trough answer different clinical questions.

A high number cannot be interpreted intelligently without knowing:

• when it was drawn
• what formulation the patient uses
• how the patient feels
• what the safety markers show

The first pellet cycle is a calibration cycle

Follow-up testing shows how a particular patient absorbed a particular dose and helps determine whether the next cycle should use a different dose or interval.

This is individualized pharmacokinetic data — not simply a pass/fail test against a generic reference range. Learn how pellet insertion and follow-up work on our Hormone Pellet Therapy page.

Compounded testosterone pellets are not FDA-approved products, but “there is no data” is inaccurate.

A 2023 randomized open-label non-inferiority trial (n=183) directly compared a compounded testosterone pellet with Testopel and found comparable serum testosterone levels and comparable adverse-event rates over the study period. [10]

Additional research has examined pellet surface area and release characteristics. [11]