Testosterone Replacement Therapy: Why I Often Prefer the Transdermal Approach

David S. Klein, MD FACA FACPM
7 days ago
9 min read

Testosterone deficiency (male hypogonadism) can quietly undermine energy, mood, libido, muscle mass, bone health, and overall quality of life. When we confirm true testosterone deficiency with appropriate testing, testosterone replacement therapy (TRT) can be transformative. Among several delivery options—injectable, oral, implantable—transdermal preparations (gels, creams, and patches) offer particular advantages: steady hormone levels, physiologic daily dosing, flexibility of titration, and non-invasive administration. Randomized trials and long-term studies show that TRT in appropriately selected men improves sexual function, bone density, muscle mass, anemia, and overall vitality, with cardiovascular safety now better defined in recent large trials and regulatory reviews.WJMH+4PMC+4OUP Academic+4

Advantages of Transdermal Hormones as opposed to Intramuscular Injection or Oral Hormones in HRT

Transdermal hormone replacement offers several physiological and clinical advantages over both injectable and oral formulations. By delivering the hormone directly through the skin and into the systemic circulation, transdermal therapy bypasses first-pass hepatic metabolism — a key limitation of oral preparations that can elevate liver enzymes and alter lipid profiles.

Unlike injections, which produce peaks and troughs in serum hormone levels and may provoke mood volatility or symptomatic fluctuations, transdermal delivery supports a steadier, physiological release that more closely mimics endogenous hormone secretion. This route also allows for easier titration, rapid cessation if adverse effects occur, and improved patient adherence due to its convenience and pain-free administration. Furthermore, transdermal absorption can reduce the risk of thromboembolic events associated with oral estrogens and minimize supraphysiologic spikes seen with intramuscular injections. For many patients, it represents a safer, more elegant, and more physiologic approach to hormone optimization.

Physician explains benefits of transdermal testosterone therapy, who qualifies, and why regular lab monitoring is essential for safe, effective treatment. Best testosterone therapy orlando

This blog explains—using the same language I use in the office—why I often recommend transdermal testosterone, what benefits you might reasonably expect, and why periodic laboratory monitoring is essential to keep the therapy effective and safe. I will also outline how we decide whether you are a good candidate, how we monitor blood counts, prostate markers, and hormone levels, and how recent evidence has clarified cardiovascular and blood-pressure considerations.

When men sit down and tell me they are exhausted, losing strength, gaining abdominal fat, and watching their libido fade, low testosterone is often on the short list of possibilities—but it is never the only one. Thyroid disease, sleep apnea, depression, medications, alcohol, and simple deconditioning can all look similar. That is why I do not prescribe testosterone based on symptoms alone.

Guidelines from the Endocrine Society are very clear: we should make a diagnosis of hypogonadism only when both consistent symptoms and unequivocally low morning testosterone levels on at least two occasions are present.PubMed+2Endocrine Society+2 In other words, we treat a real deficiency, not just a number or a birthday.

Once that diagnosis is made, our next decision is how to replace testosterone. That is where the advantages of the transdermal route become important.

Why transdermal testosterone has become a first-line option

Transdermal testosterone—usually in the form of gels, creams, or patches—delivers the hormone through the skin into the bloodstream. Several features make this route attractive:

Steady, physiologic hormone levels: Daily application produces relatively stable testosterone levels, avoiding the sharp peaks and troughs we often see with intermittent intramuscular injections. Prospective studies of testosterone gel show smooth pharmacokinetics and improvements in quality of life compared with injection schedules.ScienceDirect+4PubMed+4Europe PMC+4
Flexible dose titration: Because we adjust the amount of gel or cream rather than the interval between large injections, it is relatively easy to fine-tune the dose so that your blood level sits in the mid-normal range—high enough to relieve symptoms but not excessive. This titration strategy is supported by controlled trials of 1.62% testosterone gel demonstrating that most hypogonadal men can be brought into the eugonadal range with dose adjustments.PubMed+1
Non-invasive and convenient: Many men simply prefer not to have injections every 1–12 weeks. With transdermal therapy, your “injection” is replaced by a daily morning routine applied to clean, dry skin. For travel, work, and general day-to-day life, this can be substantially more convenient.
Physiologic daily: a physiologic perspective, providing testosterone every day better mimics normal testicular secretion than large, intermittent boluses. Though several modern long-acting injection formulations are excellent therapies, transdermal treatment remains a very reasonable “default” choice for many men, especially those new to TRT.American Academy of Family Physicians+2Wiley Online Library+2

What benefits can you realistically expect?

When testosterone is genuinely low and replaced to normal levels, we see several consistent benefits across randomized trials and meta-analyses:

Improved libido and sexual function TRT improves sexual desire, erectile function, and overall sexual satisfaction in hypogonadal men.OUP Academic+1
More energy, better mood, improved sense of well-being Many men describe a gradual return of “drive” and resilience. Systematic reviews report modest but meaningful improvements in mood and subjective vitality in appropriately treated patients.PMC+1
Increased muscle mass and reduced fat mass Testosterone is a key anabolic hormone. Replacement therapy increases lean body mass and decreases visceral adiposity, particularly when combined with resistance exercise and appropriate diet.PMC+1
Bone health and fracture risk Testosterone replacement improves bone mineral density in hypogonadal men and, in recent large trials, has been associated with reduced fracture risk when combined with standard osteoporosis care.Bioscientifica+1
Correction of anemia in some men TRT can stimulate red blood cell production. In hypogonadal men with otherwise unexplained anemia, treatment has been shown to improve hemoglobin and hematocrit levels.JAMA Network+1

There are also more specialized benefits. For example, small studies of transdermal testosterone suggest improved angina threshold in men with chronic stable angina, likely through vasodilatory and metabolic mechanism.

Of course, these benefits are not guaranteed for every man, and they must always be weighed against potential risks and the burden of monitoring.

Safety: what we know now about cardiovascular and other risks

For several years, testosterone therapy carried an FDA warning regarding a possible increased risk of cardiovascular events. More recent high-quality data have clarified this picture.

The large TRAVERSE trial and related analyses found that in middle-aged and older hypogonadal men at increased cardiovascular risk, testosterone therapy was non-inferior to placebo for major adverse cardiovascular events when used appropriately.WJMH+1 In 2025, the FDA updated labeling for testosterone products to reflect these data, removing language suggesting an overall increased cardiovascular risk while adding required warnings about potential increases in blood pressure with certain formulations.Reuters

There are still important safety considerations:

Erythrocytosis (high hematocrit) is the most common lab abnormality on TRT and is a dose-related effect. Meta-analyses show a clear increase in elevated hematocrit among treated men, which is why regular blood count monitoring is non-negotiable.OUP Academic+1
Prostate health must be monitored. In men without known prostate cancer, TRT has not been shown to meaningfully increase prostate cancer incidence in the short to medium term, but it can increase biopsy rates and slightly raise PSA, hence the need for routine PSA and digital rectal examination (DRE) according to age-appropriate guidelines.Frontiers+2American University Alumni Network+2
Skin-to-skin transfer risk is unique to transdermal preparations. Testosterone gel can be transferred to partners or children if the application site is not covered; this is preventable with proper precautions—washing hands, allowing the gel to dry before dressing, and keeping the area covered.FDA Access Data

When we select patients carefully, stay within physiologic dosing, and monitor regularly, the overall risk-benefit balance for men with true hypogonadism is generally favorable.

Why periodic laboratory monitoring is essential—not optional

I tell every patient starting testosterone: the prescription and the lab schedule are a package deal. You do not get one without the other.

Most evidence-based protocols and consensus guidelines recommend the following approach:PubMed+3NCBI+3Endocrine Society+3

Before starting treatment
- Two separate morning total testosterone measurements (usually before 10 a.m.)
- LH and FSH to distinguish primary from secondary hypogonadism
- Hematocrit/hemoglobin
- PSA and DRE in men over about 40–50, or younger with risk factors
- Consider lipid profile, fasting glucose or A1C, liver function tests, and in some settings estradiol and SHBG
3–6 months after starting or changing dose
- Serum testosterone level, checked after steady state is reached (for gels, typically after 2–4 weeks of consistent use); we aim for a mid-normal range
- Hematocrit/hemoglobin
- PSA and DRE as appropriate
- Re-assessment of symptoms, blood pressure, and any adverse effects
Annually thereafter (or more often if needed)
- Testosterone level
- Hematocrit/hemoglobin
- PSA and DRE
- Periodic bone density testing in men with osteoporosis or high fracture risk

If hematocrit rises above about 54%, we hold therapy, look for contributing factors (sleep apnea, smoking, dehydration), and restart at a lower dose or switch routes once the level normalizes.NCBI+2MD Edge+2

This monitoring is not busywork; it is the mechanism by which we turn testosterone from a blunt instrument into a precise treatment.

Practicalities of using transdermal testosterone replacement therapy

From a day-to-day standpoint, I coach men through a few key steps:

Apply once daily in the morning to clean, dry, unbroken skin—commonly shoulders, upper arms, or upper chest, depending on the formulation.
Allow it to dry fully before dressing.
Wash your hands thoroughly after application.
Cover the application site with clothing to reduce the risk of transfer to others.
Avoid showering or swimming for the period recommended in the product labeling (often a few hours) to ensure adequate absorption.FDA Access Data

We then adjust the dose based on both your symptoms and your blood levels. If you report feeling “flat” in the late afternoon but your levels are high-normal, we do not chase subjective energy with supraphysiologic dosing; instead, we look for other causes—sleep, nutrition, comorbidities.

Who is not an ideal candidate?

Even the best therapy is not for everyone. Men with any of the following need special consideration or should generally avoid TRT:

Known or suspected prostate or breast cancer. Use with appropriate caution.
Markedly elevated PSA or abnormal DRE not yet evaluated
Severe untreated obstructive sleep apnea
Uncontrolled heart failure or recent major cardiovascular events (where guidelines recommend individualized risk–benefit discussion)
Very high hematocrit at baseline

For men with age-related borderline low testosterone and minimal symptoms, current guidelines and FDA labeling urge caution; indiscriminate use in otherwise healthy men is not recommended.Endocrine Society+2OUP Academic+2

Bringing it all together

Testosterone replacement therapy, when used judiciously, can restore much of what hypogonadism has quietly taken away: sexual function, strength, bone integrity, and a sense of vitality. Transdermal preparations offer a highly practical and physiologic way to deliver that hormone—daily, non-invasively, and with the flexibility to fine-tune dosing to your individual needs.

But TRT is not a lifestyle supplement; it is a prescription hormone therapy that demands a structured diagnostic process and ongoing laboratory monitoring. If we respect those requirements, we can maximize the likelihood that you enjoy the benefits while minimizing risk.

If you recognize some of the symptoms described here, the next step is not to start testosterone on your own; it is to have a thorough conversation with a clinician who understands both the promise and the limits of this therapy—and who is committed to monitoring you properly over time.

Selected References

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. https://pubmed.ncbi.nlm.nih.gov/29562364 PubMed+1
Endocrine Society. Testosterone Therapy for Hypogonadism Guideline Resources. March 19, 2018. https://www.endocrine.org/clinical-practice-guidelines/testosterone-therapy Endocrine Society+1
Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009;5(3):427-448. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701485 PMC
Petering RC, Brooks NA. Testosterone therapy: review of clinical applications. Am Fam Physician. 2017;96(7):441-449. https://www.aafp.org/pubs/afp/issues/2017/1001/p441.html American Academy of Family Physicians
Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med. 2011;8(7):2079-2089. https://pubmed.ncbi.nlm.nih.gov/21492400 PubMed+1
Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C. One-year efficacy and safety study of a 1.62% testosterone gel for hypogonadal men. J Sex Med. 2012;9(1):209-219. https://pubmed.ncbi.nlm.nih.gov/22321357 PubMed
Scott JD, Murdoch FE, Mudge DW. Prospective study of topical testosterone gel (AndroGel) versus intramuscular testosterone in the treatment of hypogonadal men. Aust N Z J Med. 2007;37(3):268-272. https://pubmed.ncbi.nlm.nih.gov/18042506 PubMed+1
Mwamba RN, et al. The efficacy, safety, and outcomes of testosterone use in hypogonadal men. Neurourol Urodyn. 2023;42(4):887-899. https://onlinelibrary.wiley.com/doi/10.1002/nau.25094 Wiley Online Library
Kalra S, et al. Testosterone replacement in male hypogonadism. Indian J Endocrinol Metab. 2010;14(Suppl 2):S89-S94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262378 PMC
Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N, et al. Efficacy and adverse events of testosterone replacement therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018;103(5):1745-1754. https://academic.oup.com/jcem/article/103/5/1745/4939466 OUP Academic
Hackett GI. Long-term cardiovascular safety of testosterone therapy. World J Mens Health. 2025;43(2):e11. https://wjmh.org/DOIx.php?id=10.5534/wjmh.240081 WJMH
Snyder PJ, Bhasin S, Cunningham GR, et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med. 2024;390(5):421-433. https://www.nejm.org/doi/full/10.1056/NEJMoa2308836 New England Journal of Medicine
Pencina KM, D’Agostino RB, Basaria S, et al. Efficacy of testosterone replacement therapy in improving anemia in men with hypogonadism. JAMA Netw Open. 2023;6(8):e2328153. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811115 JAMA Network
Bhasin S. Testosterone therapy in men with hypogonadism: monitoring recommendations. In: Testosterone Therapy in Men with Hypogonadism – An Endocrine Society Clinical Practice Guideline (plenary slides). Endocrine Society; 2018. Table: “Recommendations for Monitoring of Men Receiving Testosterone Therapy.” https://www.ncbi.nlm.nih.gov/books/NBK278998/table/age-rel-chang-mra.T.recommendations_for/ and https://www.endocrine.org/-/media/endocrine/files/cpg/testosterone-therapy-plenary-6-1-18_online.pdf MD Edge+3NCBI+3Endocrine Society+3
U.S. Food and Drug Administration. Labeling changes for testosterone products based on cardiovascular outcomes and blood pressure studies. Reuters summary, Feb 28, 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/fda-issues-labeling-changes-testosterone-products-2025-02-28/ Reuters