Physiology cares about patterns, not promises.
By Prof. MarkAnthony Nze
Forms, Dosing, and Delivery: Why How You Take Testosterone Matters as Much as Whether You Take It
A man in an airport lounge rolls up his sleeve like he’s about to confess something. Not dramatically—just enough to expose the thickened skin near his deltoid, the faint bruise that comes and goes like a private weather system. He’s learned to do injections fast. No hesitation. No ceremony. If he lingers, he thinks too much, and thinking—he’s discovered—is the enemy of compliance.
Across the room, another man is doing the opposite ritual: pressing a clear gel into his shoulder with the deliberate care of someone applying sunscreen to a scar. He waits for it to dry. He checks his phone. He doesn’t say it, but he’s thinking about his kids. About the towel they might grab. About whether the drug that is supposed to stabilize his life could accidentally brush into theirs.
Same hormone. Two methods. Two wildly different physiological stories.
This is the detail most testosterone conversations skip: TRT is not a single therapy. It is a family of delivery systems, each with its own pharmacokinetic “accent,” its own risk profile, and its own psychology. The molecule might be the same. The body’s experience is not.
If Parts 1–5 were about what testosterone is, how to test it, how lifestyle shapes it, and who TRT is for, Part 6 is about the part that often determines whether TRT becomes a measured medical tool—or a swinging pendulum that turns your mood, blood pressure, hematocrit, and relationships into collateral.
And before we go further, a quiet acknowledgement: many men first encounter these concepts through popular health writing—sometimes helpful, sometimes overly neat. The public-facing series framing “male menopause” and prostate considerations captures the basic arc—hormones, aging, tradeoffs—but the deeper truth is more granular: route and rhythm matter (Africa Digital News, New York, 2026a; Africa Digital News, New York, 2026b; Africa Digital News, New York, 2026c; Africa Digital News, New York, 2026d; Africa Digital News, New York, 2026e).
Let’s get forensic about it.
Read also: Male Menopause & Prostate: What Men Should Know—Part 5
The myth of “Same hormone, same outcome”
Here’s the seductive oversimplification: “It’s testosterone. Once it’s in your body, it’s the same.”
That’s like saying coffee is coffee, so espresso and a slow drip should affect you identically. Anyone who’s ever misjudged a double shot knows the flaw immediately.
Route of administration changes biology because it changes:
● how quickly testosterone rises,
● how high it peaks,
● how low it falls before the next dose,
● what tissues see, and for how long,
● and which side effects become more likely.
In clinical language, these are pharmacokinetics (PK): absorption, distribution, metabolism, elimination. In human language: the hormone’s shape in time.
And time-shape matters because hormones aren’t just “levels.” They’re signals. Your tissues don’t merely read the number; they respond to the pattern.
A smooth, physiological pattern tends to be easier on mood stability and can simplify monitoring. A spiky pattern can generate a cycle: energy surges, libido spikes, irritability rises, sleep shifts, then a crash that feels like the return of the original problem—prompting dose escalation, which worsens the spike. That’s the loop where good intentions go to die.
Peaks, troughs, and symptom volatility: the hidden driver of “TRT drama”
When men say “TRT stopped working,” they often mean one of three things:
1. They’re in a trough—their levels have dropped, and their body is telling the truth about it.
2. They’re chasing the peak—they’ve become accustomed to the high, and normal feels like failure.
3. The upstream issues returned—sleep, stress, metabolic health—and testosterone was never going to be enough on its own.
Delivery method doesn’t determine which of these happens, but it changes the odds.
This is why “how you take testosterone” becomes as important as “whether you take it.” In a well-run endocrine practice, a clinician doesn’t just prescribe testosterone; they prescribe a pattern.
Injectables: power, precision, and pitfalls
Injectables are popular for a reason: they work, they’re efficient, and they are often cost-effective. They also hand you a loaded instrument.
Weekly vs bi-weekly vs micro-dosing: it’s not preference, it’s waveform engineering
Traditional schedules—especially longer intervals—can produce higher peaks and deeper troughs. Some men tolerate this well. Others become emotional barometers: confident, driven, borderline euphoric at the peak; flat, anxious, low-libido at the trough. Their lives start to orbit the injection calendar.
That volatility isn’t imagined. It’s pharmacology behaving exactly as you’d expect.
The question isn’t “What schedule do I like?” It’s “What pattern does my physiology handle without collateral damage?”
Why supraphysiologic peaks matter
A peak above physiological range is not a badge of success; it’s a risk multiplier. Peaks can amplify side effects and make monitoring harder. Men often mistake “feeling amazing” for “being healthy,” but those are separate categories. Health is quieter than that.
One of the sharpest underappreciated risks associated with testosterone therapy is erythrocytosis—an increase in red blood cell mass reflected as elevated hematocrit. While erythrocytosis can occur across modalities, higher peaks may increase risk in susceptible individuals. A 2024 analysis interrogated whether phlebotomy is a justified response to TRT-induced erythrocytosis, highlighting that routine blood-letting as a “fix” is not a trivial decision and deserves more evidence than casual practice sometimes gives it (Bond et al., 2024). Translation: if your plan for rising hematocrit is “we’ll just drain some blood,” you’re already in a more complicated medical arrangement than most men realize when they sign up for TRT.
Read also: Male Menopause & Prostate: What Men Should Know—Part 4
Mood, hematocrit, and cardiovascular considerations: the monitoring triangle
People love to debate whether TRT is “heart safe.” The adult conversation is more nuanced: it depends on who you are, how you’re dosed, how your blood pressure responds, how your hematocrit moves, and whether your metabolic risk is being addressed.
We have stronger evidence now on major cardiovascular outcomes in appropriately selected men (Lincoff et al., 2023). But that doesn’t erase the importance of the mechanisms that can still matter day-to-day—like blood pressure changes.
And blood pressure is not theoretical. Ambulatory blood pressure monitoring (ABPM) studies have documented blood pressure effects with certain testosterone therapies, including transdermal modalities (Efros et al., 2024; Weber et al., 2025) and oral testosterone undecanoate (White et al., 2021a; White et al., 2021b). What this tells you is simple: route matters, and the cardiovascular system notices.
If a clinic prescribes injectables without a plan to track hematocrit and blood pressure with real seriousness, the clinic is not practicing modern TRT. It’s practicing testosterone optimism.
Transdermal therapies: gels and patches (stability with strings attached)
If injections are a drumbeat—loud, periodic—transdermals aim for a more continuous hum.
The advantage: a steadier pattern, often fewer dramatic peaks
Transdermal gels and patches can produce more stable daily levels, which some men experience as calmer mood and fewer “on/off” days. For men who are sensitive to swings, transdermal therapy can feel like trading a roller coaster for a commuter train.
But the commuter train still has delays.
Absorption variability: the quiet frustration of “I’m doing it right”
Transdermal absorption varies with skin characteristics, application technique, sweating, bathing timing, and individual physiology. Two men can apply the same amount and get meaningfully different serum levels.
That variability makes transdermal therapy feel psychologically tricky: the ritual is daily and disciplined, yet outcomes can still surprise. Some men interpret that as failure. It’s not failure—it’s biology.
ABPM studies focusing on men treated with testosterone transdermal therapy underscore that even “steady” routes can have measurable physiological impacts, including on blood pressure (Efros et al., 2024; Weber et al., 2025). Stability does not equal neutrality.
Household transfer risks: the side effect nobody wants to talk about
This is where the gel story becomes domestic. Transfer risk is not paranoia. Testosterone gel can be transferred through skin contact, towels, bedding, or inadvertent contact—posing risk to partners and children. The precautions are manageable, but they are real, and they require a level of diligence that some households can sustain and others cannot.
This is why route choice is not only medical. It’s social architecture. If you live with toddlers who climb like monkeys and hug like it’s their job, your therapy plan needs to account for that reality.
Long-acting preparations and pellets: convenience versus reversibility
Long-acting formulations and pellets are often marketed with the promise that men crave most: freedom from thinking about it.
That promise is understandable. It’s also where danger hides.
The appeal: fewer decisions, fewer reminders
Long-acting treatments can reduce the constant cognitive load of TRT: fewer injections, fewer daily applications. For some men, that means better adherence and better stability.
The risk: “set it and forget it” can become “set it and regret it”
The key problem is reversibility. If you have an adverse effect—hematocrit rises, blood pressure worsens, mood destabilizes—you want the option to adjust quickly. With long-acting approaches, adjustments can be slower, and the “off switch” is less immediate.
A review looking at long versus short-acting testosterone treatments emphasizes that risk profiles differ across delivery methods and that the tradeoffs are not trivial (Gurayah et al., 2023). The broader principle is almost philosophical: the more convenient the intervention, the more carefully you must engineer its safety exits.
In practice, pellets and long-acting formulations are best reserved for men who have already demonstrated stable benefit and stable monitoring on more adjustable forms. Starting a complicated pattern with a hard-to-reverse modality is like learning to drive on black ice.
Oral and alternative forms: the return of a once-troubled idea
Oral testosterone has a complicated history. For years, “oral testosterone” carried an implicit warning: liver toxicity concerns, inconsistent absorption, and unfavorable risk-benefit profiles.
So why is oral therapy back in the conversation?
Because formulation science is stubborn—and because men want options.
Why most oral testosterones failed historically
Traditional oral androgens encountered first-pass hepatic metabolism issues and adverse liver effects. That history matters because it teaches skepticism: just because something is easier doesn’t mean it’s safer.
A 2022 historical perspective on novel oral agents for testosterone replacement therapy traces this evolution and why earlier oral approaches were limited (Kanabur et al., 2022).
Oral testosterone undecanoate (TU): promise with scrutiny
Modern oral testosterone undecanoate formulations have been studied in contemporary trials assessing pharmacokinetics, safety, and efficacy (Bernstein & Dhingra, 2024; Miner et al., 2024). The story here is not “oral is perfect now.” It’s “oral is plausible, but it has specific physiological signatures.”
One signature that has drawn attention is blood pressure. ABPM studies have documented blood pressure changes with oral TU formulations (White et al., 2021a; White et al., 2021b). And even recent reviews of newer oral TU formulations highlight ongoing safety considerations, including historical liver side-effect concerns and the need for continued vigilance (Goldstein et al., 2025).
This is the correct stance: curious, not credulous.
Oral TU may be a good option for some men—especially those who dislike needles or cannot manage transdermal precautions—but it is not a get-out-of-monitoring card. It is a different route with different monitoring priorities.
Dosing philosophy: less is often more (and “more” is often a nervous system problem)
Most dosing disasters begin with a cultural assumption: if something is good, more must be better.
Endocrinology laughs at that assumption.
Target physiologic levels, not maximal levels
The goal of TRT is typically to restore testosterone to a physiologic range that alleviates symptoms while minimizing adverse effects. In real-life practice, symptom relief often plateaus at a certain range. Past that, you may accumulate risk without adding meaningful wellbeing.
The more sophisticated question isn’t “How high can we get it?” It’s “What is the lowest dose that gives durable, meaningful function with tolerable risk?”
Why symptom relief plateaus before risk does
This is one of the cruel truths of medicine: benefits often arrive early; risks accumulate quietly. A man may feel fantastic at higher levels—until hematocrit rises, blood pressure creeps up, sleep worsens, or mood becomes brittle.
Blood pressure findings across ABPM studies are a case in point: physiological systems can shift even when you feel “fine” (Efros et al., 2024; Weber et al., 2025; White et al., 2021a; White et al., 2021b).
The steady clinician’s job is to protect you from your own short-term enthusiasm. The steady patient’s job is to accept that protection as respect, not restriction.
Individualization over algorithms: why identical doses yield different outcomes
Two men can take the same testosterone dose in the same form and end up in entirely different biological neighborhoods. This is not mysterious. It’s physiology.
Key reasons include:
● Body composition: adiposity affects distribution and metabolism.
● SHBG differences: binding proteins change how total and free levels relate.
● Metabolic rate and liver function: influence metabolism and clearance.
● Skin absorption variability: especially for transdermals.
● Cardiovascular baseline: determines sensitivity to BP changes.
● Genetic and tissue-level sensitivity: changes response even at similar serum levels.
This is why personalization is not luxury; it’s necessity.
And it is also why the clinician who promises a universal “protocol” is advertising certainty they cannot honestly deliver.
A contemporary overview asking “where are we in 2025?” underscores how the field continues to evolve—new formulations, new evidence, and ongoing debates about best practices (Walia et al., 2025). That evolution is not a weakness. It’s a sign that serious medicine keeps updating itself.
A practical map: choosing a delivery method like a grown-up
Here is a decision logic that respects both biology and real life—without pretending there is one perfect option.
Consider injectables when:
● cost and reliability matter,
● you can tolerate periodic dosing,
● you’re willing to manage swings via schedule optimization,
● and you’ll monitor hematocrit and blood pressure seriously (Bond et al., 2024).
Consider transdermals when:
● you want steadier daily levels,
● you are sensitive to peaks/troughs,
● you can manage transfer precautions,
● and you accept absorption variability (Efros et al., 2024; Weber et al., 2025).
Consider longer-acting approaches/pellets when:
● you’ve already proven stable benefit and stable labs on adjustable forms,
● you prioritize convenience,
● and you understand reversibility constraints (Gurayah et al., 2023).
Consider oral TU when:
● needles and gels are impractical,
● you can commit to BP monitoring,
● and you accept that “oral” doesn’t mean “lightweight” (White et al., 2021a; White et al., 2021b; Bernstein & Dhingra, 2024; Miner et al., 2024; Goldstein et al., 2025).
There is no shame in any route. There is only wisdom or carelessness in how you choose.
The investigative punchline: TRT failures are often pattern failures
If you wanted the single sentence most clinics won’t print on their brochures, it’s this:
A surprising number of “TRT problems” are really “TRT pattern problems.”
Men don’t necessarily need “more testosterone.” They need:
● fewer peaks that spike hematocrit,
● fewer troughs that create symptom panic,
● less dose chasing,
● better blood pressure awareness,
● and a delivery method that fits the physics of their life.
This is why “physiology cares about patterns, not promises” isn’t a slogan. It’s an operating principle.
In the earlier parts of this series, the emphasis was on diagnosis, testing, and who truly qualifies for therapy. Now we add the next layer: even a correct diagnosis can be undermined by a reckless delivery strategy.
TRT is not just a prescription. It is an engineered rhythm. And like any rhythm, it either supports the structure of your life—or it starts to conduct it.
Bridge to Part 7
Part 7 is where TRT becomes a long game: monitoring as a form of intelligence, not anxiety. We’ll cover the living reality of TRT—how to track it responsibly, what red flags mean, how to respond to rising hematocrit or blood pressure, and how to know when the smartest move is to adjust, pause, or stop.
Professor MarkAnthony Ujunwa Nze is an internationally acclaimed investigative journalist, public intellectual, and global governance analyst whose work shapes contemporary thinking at the intersection of health and social care management, media, law, and policy. Renowned for his incisive commentary and structural insight, he brings rigorous scholarship to questions of justice, power, and institutional integrity.
Based in New York, he serves as a full tenured professor and Academic Director at the New York Center for Advanced Research (NYCAR), where he leads high-impact research in governance innovation, strategic leadership, and geopolitical risk. He also oversees NYCAR’s free Health & Social Care professional certification programs, accessible worldwide at:
https://www.newyorkresearch.org/professional-certification/
Professor Nze remains a defining voice in advancing ethical leadership and democratic accountability across global systems.
Selected Sources (APA 7th Edition)
Africa Digital News, New York. (2026, February 7). Male Menopause & Prostate: What Men Should Know—Intro. https://africadigitalnewsnewyork.com/2026/02/07/male-menopause-prostate-what-men-should-know-intro/
Africa Digital News, New York. (2026, February 8). Male Menopause & Prostate: What Men Should Know—Part 1. https://africadigitalnewsnewyork.com/2026/02/08/male-menopause-prostate-what-men-should-know-part-1/
Africa Digital News, New York. (2026, February 9). Male Menopause & Prostate: What Men Should Know—Part 2. https://africadigitalnewsnewyork.com/2026/02/09/male-menopause-prostate-what-men-should-know-part-2/
Africa Digital News, New York. (2026, February 10). Male Menopause & Prostate: What Men Should Know—Part 3. https://africadigitalnewsnewyork.com/2026/02/10/male-menopause-prostate-what-men-should-know-part-3/
Africa Digital News, New York. (2026, February 11). Male Menopause & Prostate: What Men Should Know—Part 4. https://africadigitalnewsnewyork.com/2026/02/11/male-menopause-prostate-what-men-should-know-part-4/
Bernstein, J. S., & Dhingra, O. P. (2024). A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Therapeutic Advances in Urology, 16, 17562872241241864.
Bond, P., Verdegaal, T. A., Smit, D. L., & de Vries, F. (2024). Testosterone therapy-induced erythrocytosis: Can phlebotomy be justified? Endocrine Connections, 13(10), EC-24-0283.
Efros, M. D., Kaminetsky, J. C., Sherman, N. D., Chan, A., & Thomas, J. W. (2024). Ambulatory blood pressure parameters among men with hypogonadism treated with testosterone transdermal therapy. Endocrine Practice, 30(9), 847–853.
Goldstein, I., Chidambaram, N., Dobs, A., King, S., Miner, M., Ramasamy, R., Yafi, F. A., & Khera, M. (2025). Newer formulations of oral testosterone undecanoate: Development and liver side effects. Sexual Medicine Reviews, 13(1), 33–40.
Gurayah, A. A., Dullea, A., Weber, A., Masterson, J. M., Khodamoradi, K., Mohamed, A. I., & Ramasamy, R. (2023). Long vs short acting testosterone treatments: A look at the risks. Urology, 173, 18–25.
Kanabur, P., Brunner, R., Khera, D., Flores, H. A., & Khera, M. (2022). The evolving role of novel oral agents for testosterone replacement therapy: A historical perspective. Androgens: Clinical Research and Therapeutics, 3(1), 224–232.
Lincoff, A. M., Bhasin, S., Flevaris, P., et al. (2023). Cardiovascular safety of testosterone-replacement therapy. The New England Journal of Medicine, 389(2), 107–117.
Miner, M., Wang, C., Khera, M., Carson, C., Chidambaram, N., King, S., & colleagues. (2024). Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism. Andrology.
Weber, M. A., Aslam, S., Efros, M. D., Chan, A., Khan, N., Li, X., Dubcenco, E., & Miller, M. G. (2025). Single-arm study of testosterone gel replacement therapy and ambulatory blood pressure outcomes in men with hypogonadism. Andrology, 13(6), 1390–1401.
Walia, A., Coady, P., Sofia-Hernandez, B., et al. (2025). Testosterone replacement, where are we in 2025? Trends in Urology & Men’s Health, 16(6), 1–10.
White, W. B., Dobs, A., Carson, C., et al. (2021a). Effects of a novel oral testosterone undecanoate on ambulatory blood pressure in hypogonadal men. Journal of Cardiovascular Pharmacology and Therapeutics, 26(6), 630–637.
White, W. B., Bernstein, J. S., Rittmaster, R., et al. (2021b). Effects of oral testosterone undecanoate on ambulatory blood pressure in hypogonadal men. The Journal of Clinical Hypertension, 23(7), 1420–1430.*
