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Testosterone Therapy: Cardiovascular Safety & Oral Innovation

Written by Access Medical Labs | Aug 5, 2025 4:39:10 PM

For many men, the idea of starting testosterone therapy comes with hesitation—and often, fear. Will it raise blood pressure? Increase clotting risk? Trigger prostate issues? These concerns have lingered for decades, fueled by early studies that left more questions than answers.

But times—and science—have changed. More recent research, presented by Dr. Andrew Sun (Director of the Center for Men's Health at Urology Partners of North Texas) in a recent Access Live is challenging the old narratives, showing that physiologic testosterone therapy, when monitored carefully, may not only be safe, but supportive of long-term health. And thanks to the arrival of next-generation oral testosterone, there’s now a simpler, more biologically aligned way to offer hormone support without sacrificing safety or fertility.


“Oral Testosterone Undecanoate brings testosterone therapy closer to biological reality. It preserves more natural signaling while delivering consistent symptom relief.”

— Dr. Andrew Sun, Access Live 2025

Here's what you'll find in this article:



Testosterone and the Heart: Clearing the Air

Much of the early concern about testosterone and heart health came from observational studies fraught with methodological flaws that lumped together very different patient groups. In many cases, the data didn’t distinguish between men using medically supervised therapy and those abusing anabolic steroids. 

When you look at more recent, better-controlled studies, the results tell a different story:

  • Blood pressure generally stays stable in men on physiologic TRT
  • Clotting risk (including VTE) does not increase after starting therapy—in fact, it may decline over time
  • Testosterone appears to support vascular health by improving nitric oxide availability, modulating the RAAS system, and lowering inflammatory clotting markers like fibrinogen and PAI-1

“The enduring narrative that testosterone causes hypertension or thrombosis is unsupported by current scientific literature.” — Dr. Mark L. Gordon, MD
Neuroendocrinology and Integrative Physiology

Prostate Health: Looking Beyond Testosterone

Another major concern that often stops therapy before it starts is prostate cancer. But here too, the story has shifted.

In a now well-cited 2004 New England Journal of Medicine study, researchers found no link between higher testosterone levels and increased prostate cancer risk. In fact, low testosterone may be more frequently associated with aggressive disease.

A 2011 Journal of Urology review came to a similar conclusion: testosterone replacement, when prescribed appropriately, doesn’t raise the risk of prostate cancer—and might even offer benefits for tissue integrity and symptom relief.


“Testosterone isn’t the problem. It’s how your body metabolizes it—especially into DHT and estradiol—that matters most.”— Dr. Mitch Ghen

True Health News: Testosterone Therapy & Prostate Cancer


That’s why monitoring downstream metabolites is so important. Elevated DHT and unbalanced estradiol—not total testosterone itself—are more likely to be the culprits when prostate concerns arise.
 

 

Rethinking Testosterone Delivery 

Testosterone therapy has traditionally been delivered through injections or transdermal gels. While both approaches have helped many men manage symptoms of hypogonadism, they come with limitations. Injections often create unnatural peaks and troughs in hormone levels, may completely suppress endogenous testosterone production, and can raise hematocrit or dihydrotestosterone (DHT). Topical gels, while more stable for some, may be less predictable in absorption and pose risks of transference.
Oral testosterone undecanoate (TU) represents an alternative delivery route that differs significantly from older oral formulations.

 

How Oral TU Works

Unlike earlier oral testosterone, which was associated with liver toxicity due to first-pass hepatic metabolism, TU is absorbed via the lymphatic system. This pathway bypasses the liver, improving bioavailability and minimizing hepatic strain.

Clinical Characteristics of Oral TU:

  • Liver-Sparing: TU avoids first-pass liver metabolism, reducing hepatotoxicity risk observed in previous oral formulations.
  • Circadian-Friendly Dosing: Taken twice daily, TU can be timed to align more closely with the body’s natural testosterone rhythm.
  • Fertility Considerations: Studies suggest that TU may partially preserve luteinizing hormone (LH) and follicle-stimulating hormone (FSH) activity, which may help maintain testicular function in some patients.
  • Potentially Fewer Side Effects: When compared to injectable testosterone, some patients report lower incidence of acne, polycythemia, and androgenic side effects like hair thinning.

Patient Adaptation

Some patients choose to take the second dose earlier in the day to better match their energy and activity levels, allowing serum testosterone to decline naturally in the evening—a pattern more reflective of endogenous production.

“I consider oral TU a first-line option—especially for testosterone-naïve men who want a more physiologic and fertility-friendly treatment.”
— Dr. Andrew Sun, Access Live 2025

Who It's For—and When to Be Cautious

Oral TU isn’t for everyone, but it fits seamlessly into a growing number of patient care plans.

Best Fit:

  • Men new to TRT, especially those looking for a non-injectable option
  • Patients hoping to preserve fertility or minimize testicular suppression
  • Individuals who’ve struggled with side effects from injections or gels
  • Men using GLP-1s or in weight-loss protocols who want to protect muscle mass

 

Use With Care:

  • Those with advanced liver dysfunction, despite non-hepatic absorption
  • Individuals seeking bodybuilding-level dosing—oral TU is therapeutic, not supraphysiologic

 

Monitoring: What (and When) to Test

One of the most common mistakes with oral TU? Fasting labs. Unlike injectables, this formulation needs to be taken with food—and lab timing matters.

“If labs look low but the patient feels great, always ask: Did they take their morning dose? Was it with enough fat? Timing matters more than most realize.”
— Dr. Andrew Sun , Access Live 2025

Dr. Sun recommends drawing labs 2–4 hours after dosing, ideally with a meal that includes some fat. This provides a more accurate picture of circulating hormone levels.

Key Panels:

Male Hormone Panel

 

Comprehensive Hormone Panel


These labs help you tailor dosing, catch metabolite imbalances, and ensure patient safety—especially in men at risk for cardiovascular or prostate complications.

Takeaways for Clinical Practice

  • Testosterone therapy, when dosed physiologically and monitored well, has not been shown to increase cardiovascular or prostate risk.
  • Oral TU offers a more natural, patient-aligned option—with better compliance, fewer side effects, and preserved fertility.
  • Specialty hormone panels from Access Medical Labs give you the data needed to optimize therapy safely and precisely.

“With oral TU, we’re not just replacing testosterone—we’re optimizing it in a way that respects how the body was designed to function.”
— Dr. Andrew Sun , Access Live 2025

References:

Disclaimer: Content on the Access Medical Labs blog is for informational purposes only and reflects the views of individual contributors, not necessarily those of Access Medical Labs. We do not endorse specific treatments, products, or protocols. This content is not a substitute for professional medical advice. Always consult a qualified healthcare provider regarding any medical concerns.