There is a particular category of medical treatment that spends decades accumulating evidence before the clinical establishment grudgingly acknowledges that the evidence was, in fact, pretty good all along. Testosterone replacement therapy has been in this category for roughly the past thirty years, and the situation in 2025 looks markedly different from the anxiety-laden prescribing environment that prevailed even a decade ago.
The headline version: TRT is one of the most prescribed hormone therapies in the United States, the major safety concern that haunted the field for over a decade has been substantially resolved by a well-designed trial, and the clinical guidelines have been updated to reflect what the evidence actually says rather than what various professional organizations feared it might say. This is progress.
The more complicated version: significant prescribing gaps persist, diagnostic criteria still vary between organizations in ways that create real-world confusion, and somewhere between 25% and 40% of men who fill testosterone prescriptions do so without adequate diagnostic evaluation. This is not progress.
Both versions are true simultaneously, which is the characteristic condition of any mature medical therapy.
Who Is on TRT and Why It Matters
By 2013, approximately 2.3 million American men were receiving testosterone replacement therapy — a figure that represented a tripling of TRT usage over the previous decade. The drivers of that growth were a combination of genuinely increased diagnosis of hypogonadism, improved patient awareness, and — in some fraction of cases — prescribing that outpaced the clinical evidence.
The prevalence of true hypogonadism, defined by both biochemical deficiency and clinical symptoms, varies depending on whose criteria you use and what population you study. The European Male Aging Study (EMAS), which evaluated over 3,000 men aged 40 to 79, found an overall prevalence of 2.1% when applying rigorous criteria: at least three sexual symptoms plus a total testosterone below 11 nmol/L (approximately 317 ng/dL) and a free testosterone below 220 pmol/L. The rates by decade were 0.1% in men in their 40s, 0.6% in their 50s, 3.2% in their 60s, and 5.1% in their 70s.
Those numbers look conservative compared to broader epidemiological estimates, which have ranged from 2% to 39% depending on which diagnostic criteria are applied and which symptoms are weighted. The honest answer is that the prevalence of clinically meaningful testosterone deficiency depends enormously on how “clinically meaningful” is defined, which is precisely the question the field has been arguing about for the past twenty-five years.
What is clear is that the pool of men who are undertreated remains substantially larger than the pool of men who are overtreated. Testosterone levels decline roughly 1 to 2% per year after age 40, and 75% of men maintain normal testosterone levels into old age — so hypogonadism is not simply aging. When it occurs, it produces real symptoms and measurable health consequences.
The TRAVERSE Trial: Closing the Cardiovascular Chapter
For roughly a decade, testosterone therapy carried a cardiovascular warning that cast a long shadow over prescribing. The concern originated from small studies and retrospective data suggesting elevated cardiac event rates in men on TRT. The warning was precautionary — reasonable in the absence of definitive trial data, and reasonable to remove once that data existed.
That data now exists. The TRAVERSE trial (2023), a large Phase 4 cardiovascular safety trial required by the FDA, enrolled hypogonadal men aged 45 to 80 with pre-existing or high risk of cardiovascular disease. The primary endpoint was non-inferiority of testosterone on major adverse cardiovascular events (MACE). TRT was non-inferior to placebo. The FDA subsequently removed language from the testosterone Boxed Warning regarding adverse cardiovascular outcomes.
This is a significant development, and it has already begun to shift prescribing patterns. The TRAVERSE data did identify higher rates of pulmonary embolism, atrial fibrillation, and acute kidney injury in the testosterone group — findings that warrant monitoring but represent a considerably more manageable risk profile than the broad cardiovascular warning that preceded them.
The clinical bottom line: TRT does not increase heart attack or stroke risk in the populations studied. The field can now have a much more precise conversation about actual documented risks rather than a precautionary general cardiac warning.
The Diagnostic Threshold Problem
Here is where the clinical picture gets messier. What testosterone level is low enough to treat?
The American Urological Association recommends a cutoff of 300 ng/dL. The Endocrine Society uses 264 ng/dL. The American Association of Clinical Endocrinologists sets it at 200 ng/dL. The International Society of Andrology recommends 230 ng/dL. Australian guidelines use age-adjusted ranges starting higher for younger men and declining with age.
The British Society for Sexual Medicine (BSSM), in its 2023 guidelines, recommends measuring LH, SHBG, and prolactin in symptomatic men with testosterone in the intermediate range of 8 to 12 nmol/L (approximately 230 to 346 ng/dL), with free testosterone assessment for borderline cases. Up to 20% of men with total testosterone above 300 ng/dL may still have low bioavailable testosterone when SHBG is elevated — suggesting that a single total testosterone cutoff misses a meaningful clinical population.
The practical consequence of this disagreement: a man with a total testosterone of 285 ng/dL and classic hypogonadal symptoms might be appropriately treated according to AUA guidelines, probably treated according to Endocrine Society guidelines, definitely not treated according to AACE guidelines, and in a “grey zone requiring further testing” according to BSSM guidelines. This is not a hypothetical clinical vignette. This is the actual situation millions of men face when they seek care.
What Therapy Is Actually Available
The formulation landscape in 2025 includes more options than at any previous point in the therapy’s history:
Intramuscular and subcutaneous injections: Testosterone cypionate and enanthate remain widely used. The peak-and-trough pharmacokinetics of biweekly IM injections are a well-documented limitation. Subcutaneous administration, at lower weekly doses (typically 50 to 150 mg), produces a flatter profile with comparable efficacy and is increasingly preferred in telehealth settings.
Transdermal gels and solutions: AndroGel, Testim, Fortesta, Axiron, and their generics and compounded equivalents remain the dominant transdermal format, with the secondary transfer risk that has been discussed in this series.
Transdermal sprays: The Hypospray platform, which is the delivery technology underlying Keen Meds’ product line, offers metered-dose precision and a meaningfully better transfer risk profile than conventional gels. Men’s formulations at 10 mg, 15 mg, and 20 mg. Women’s formulations at 0.5 mg, 1 mg, and 2 mg.
Intranasal testosterone (Natesto): A unique option for men concerned about fertility preservation. The short half-life allows partial maintenance of gonadotropin pulsatility; clinical trials showed 93.9% of men maintained total motile sperm counts above 5 million after 6 months.
Oral testosterone undecanoate (Jatenzo): Approved in 2019, absorbed through intestinal lymphatic transport rather than portal circulation, avoiding first-pass hepatic metabolism. Carries a Boxed Warning for blood pressure elevation.
Subcutaneous pellets: Sustained release over 3 to 6 months. Compliance guaranteed; dose adjustment impossible once implanted.
Each of these options represents a genuine clinical choice rather than a default. The era of “just pick injections or gel” has given way to something more like real personalized medicine.
The Telehealth Transformation
One development that the clinical guidelines have not fully incorporated is the degree to which telehealth has changed who accesses TRT and how. Prior to the telehealth expansion, testosterone therapy required in-person visits for diagnosis, prescription, and monitoring. The friction was sufficient that many symptomatic men simply went without treatment.
The telehealth model — clinical evaluation via asynchronous or synchronous digital encounter, compounding pharmacy fulfillment, at-home blood collection for monitoring — has substantially reduced that friction. Platforms like Keen Meds, working through clinical partners like Beluga Health, have made it possible for men to complete an initial evaluation, receive a prescription, and have it filled without a single in-person appointment.
Whether this expansion has resulted in better or worse diagnostic quality depends entirely on the platform. There are platforms that have replicated and improved upon in-person clinical rigor, and there are platforms that have essentially bypassed it. The difference matters.
The field in 2025 is more accessible, better evidenced, and more precisely tooled than at any previous point. The work of making it equitably well-practiced is ongoing.
Next up: Post 2 examines the laboratory work that actually matters in TRT management: what to measure, when to measure it, and how to interpret the numbers that come back. The labs do the talking. Post 2: The Lab Work That Matters.
