Men’s health › What TRT is
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The short version. Testosterone replacement therapy treats a diagnosis, and the diagnosis has two halves: symptoms and unequivocally low testosterone on two separate fasting morning draws. Both guidelines that matter say so. Treatment is not a course you finish — it is ongoing, it suppresses your own production and your fertility, and it commits you to blood monitoring for as long as you stay on it. The FDA changed the class labelling in 2025 in a way most articles have not caught up with.
What it is
TRT means supplying testosterone from outside the body to men whose own production is deficient. It comes as topical gels, injections, patches, pellets and buccal forms. It treats hypogonadism — it does not treat ageing, tiredness or low mood in men whose testosterone is normal.
The diagnostic bar
The Endocrine Society clinical practice guideline is direct: “We recommend diagnosing hypogonadism in men with symptoms and signs of testosterone deficiency and unequivocally and consistently low serum total testosterone and/or free testosterone concentrations.”
And the method is specified: “clinicians should measure total testosterone concentrations on two separate mornings when the patient is fasting.”
The AUA guideline commits to a number where the Endocrine Society does not:
- Statement 1: “Clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis of low testosterone.”
- Statement 2: “The diagnosis of low testosterone should be made only after two total testosterone measurements are taken on separate occasions with both conducted in an early morning fashion.”
- Statement 3: “The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs.”
- Statement 6: “In patients with low testosterone, clinicians should measure serum luteinizing hormone levels.”
What about age-related decline
Testosterone falls with age. The Endocrine Society is deliberately cautious: “We suggest against routinely prescribing testosterone therapy to all men 65 years or older with low testosterone concentrations.” Where symptoms are present, it suggests offering treatment “on an individualized basis after explicit discussion of the potential risks and benefits.”
It also recommends against screening the general male population. A marketing funnel that invites every tired man over 35 to check his levels is the opposite of that advice.
What the FDA changed in 2025 — and why most articles are out of date
On 28 February 2025 the FDA required class-wide labelling changes for testosterone products. Two changes, in opposite directions.
Removed: the agency required sponsors to “remov[e] language from the Boxed Warning related to an increased risk of adverse cardiovascular outcomes for all testosterone products.” The basis was the TRAVERSE trial, which the FDA summarised as concluding “that there was no increase in the risk of adverse cardiovascular outcomes in men using testosterone for hypogonadism.”
Added: a new blood pressure warning. “Results from the completed ABPM studies confirmed an increase in blood pressure with use of all testosterone products, class-wide.” The AndroGel label now states that blood pressure increases “can increase cardiovascular (CV) risk over time.”
This supersedes the FDA’s 2015 safety communication about heart attack and stroke risk. A great deal of material online still cites the 2015 notice as current. It is not.
What TRAVERSE actually showed
Published in the New England Journal of Medicine in 2023: 5,246 men aged 45 to 80 with existing or high-risk cardiovascular disease, hypogonadal symptoms, and two fasting testosterone measurements below 300 ng/dL, randomised to daily transdermal testosterone gel or placebo. The primary endpoint occurred in 7.0% on testosterone against 7.3% on placebo — non-inferior.
Contraindications and cautions
Absolute, from the label: “Men with carcinoma of the breast or known or suspected carcinoma of the prostate.” Testosterone products are also contraindicated in women who are pregnant.
The Endocrine Society advises against starting treatment in men with a palpable prostate nodule, PSA above 4 ng/mL (or above 3 ng/mL in men at increased risk) without urological evaluation, elevated haematocrit, untreated severe obstructive sleep apnoea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within six months, thrombophilia, or a wish to conceive in the near term.
The boxed warning on gels is about other people
Topical testosterone carries a boxed warning that has nothing to do with the man using it:
If there are children in the house, this is a practical, daily consideration. It applies to gels, not to injections.
Other risks the label names
- Polycythaemia. Raised haematocrit is the most common reason to pause treatment. The label: “An increase in red blood cell mass may increase the risk of thromboembolic events.” The Endocrine Society notes therapy can cause erythrocytosis, defined as haematocrit above 54%.
- Fertility. Exogenous testosterone suppresses your own production through feedback, reducing sperm count and shrinking the testes. The AUA requires this be discussed with anyone interested in future fertility. It is not always reversible.
- Sleep apnoea. May be potentiated, particularly with obesity.
- Prostate. Evaluation before and during treatment. Separately, AUA Statement 17: “Clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer.”
The monitoring it commits you to
Endocrine Society: measure testosterone and haematocrit “at 3 to 6 months”, again at 12 months, and annually thereafter, aiming for the mid-normal range. AUA Statement 30: “Testosterone levels should be measured every 6-12 months while on testosterone therapy.” AUA Statement 11 requires haemoglobin and haematocrit before starting, with the polycythaemia risk explained.
On PSA, the Endocrine Society sets a specific trigger for urological referral in the first 12 months: a confirmed rise of more than 1.4 ng/mL above baseline, a confirmed PSA above 4.0 ng/mL, or a prostate abnormality on examination.
A note on enclomiphene
Several online services offer enclomiphene as an alternative that raises testosterone without suppressing fertility. The regulatory facts: enclomiphene citrate is not FDA-approved for any indication. An NDA was submitted and in December 2015 the FDA issued a Complete Response Letter. At a 2022 FDA advisory committee the agency stated that “clinical trials did not demonstrate that enclomiphene citrate provides clinically meaningful improvement in symptoms or signs of hypogonadism” and flagged “cardiac and thromboembolic events, elevated estradiol, increased PSA, and increased Hct.” The committee voted 4 to 8 against adding it to the 503A bulks list.
To be precise, because precision matters here: the FDA recommended against adding it to that list and the committee agreed. We did not find an FDA enforcement statement declaring compounded enclomiphene unlawful in itself. “Not FDA-approved, and FDA recommended against its addition to the compounding list” is the accurate description — not “banned”.
Sources
- Bhasin S, Brito JP, Cunningham GR, et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” J Clin Endocrinol Metab 2018;103(5):1715–1744 — academic.oup.com
- American Urological Association, “Evaluation and Management of Testosterone Deficiency: AUA Guideline”, February 2018 — auanet.org
- FDA, “FDA issues class-wide labeling changes for testosterone products”, 28 February 2025 — fda.gov
- FDA prescribing information, ANDROGEL 1%, rev. 07/2025 — accessdata.fda.gov
- Lincoff AM, Bhasin S, Flevaris P, et al. “Cardiovascular Safety of Testosterone-Replacement Therapy.” N Engl J Med 2023;389(2):107–117 — nejm.org
- FDA Pharmacy Compounding Advisory Committee, enclomiphene citrate presentation, 8 June 2022 — fda.gov
More in the men’s health hub: how to read a testosterone test · online vs in-person care
Medical disclaimer. This article is for general information only and is not medical advice. It is not intended to diagnose, treat, cure or prevent any condition. Prescription treatments require evaluation by a US-licensed clinician, who decides whether treatment is appropriate for you. Talk to your own healthcare provider before starting, stopping or changing any medication. Individual results vary.
