Nelson Vergel
Founder, ExcelMale.com
Transcript:
Nelson Vergel: Hello, everybody. Nelson Vergel here with ExcelMale.com and DiscountedLabs.com. I'm very honored today to have one of the top urologists here in Texas. He's in Dallas, Dr. Andrew Sun. He's actually in Arlington, north of Dallas. Dr. Sun specializes in men's health, focusing on issues such as erectile dysfunction, Peyronie's disease, low testosterone, post-prostate cancer recovery, and testicular issues. He completed his undergraduate studies at the University of Maryland, medical school at Harvard, residency at the Cleveland Clinic, and a fellowship at UCLA in Male Reproductive Medicine and Surgery at the University of California, Los Angeles. So, welcome, Dr. Sun. I'm very honored to have you here. Today, we're going to speak about oral testosterone in general, specifically U Citra, trying to demystify the myths and misconceptions about oral testosterone. We previously had a product many years ago that was liver toxic, but now we're going to talk about the new paradigm and the new products coming through, approved by the FDA. This one was approved, I think, in 2021 or 2022. Dr. Sun, welcome, and he's going to give us a lecture on PowerPoint, and hopefully, we can ask him a few questions at the end. So, welcome and thanks for joining us.
Dr. Andrew Sun: Thank you so much, Nelson. It's an honor to be here with you and your group. As you kindly introduced, I am a urologist, and I exclusively practice in male sexual medicine. We have a large urology group here in the Dallas-Fort Worth area called Urology Partners of North Texas, where we have a Men's Health Center. It's a pleasure to talk to you about this new product, or rather, this new form of oral testosterone. We'll discuss the misconceptions, particularly around the term "oral testosterone," due to historical products that were liver toxic. I'll go ahead and get started. Feel free to interrupt me with any questions or anything; it should be a fun conversation. I have some slides to go through with some data to highlight the key points.
Dr. Sun (Slide Presentation): Every pharmaceutical presentation starts with a disclaimer, including the indication and black box warning from the FDA. All testosterone products carry a warning regarding high blood pressure, although the degree of increase can vary. This particular testosterone product, like others, has this warning but is still considered safe when used correctly.
Testosterone was first synthesized in 1935, and the earliest attempts at administration were oral. However, to get the testosterone to pass through the liver and into the bloodstream, it had to be methylated. Methyl testosterone, the form we used to mean when we said "oral testosterone," was very bad for the liver and was eventually taken off the market. This history has led to a persistent bias against oral testosterone. However, the new oral testosterone agents do not go through the liver and, therefore, do not have those liver toxicity issues.
What we have now are testosterone injections, first available in 1979, with various esters like cypionate, enanthate, and propionate. Topical applications came as an alternative, though they're not popular due to variability in absorption and the risk of transfer to others. Recently, we've had new products like Natesto, a short-acting nasal gel, which has been interesting in that it may allow for testosterone replacement while preserving endogenous production and potentially fertility. Another new method is an auto-injector pen for testosterone enanthate.
In 2019, a new form of oral testosterone, testosterone undecanoate, became available in the United States under different brand names, with Kyzatrex being the latest. This new formulation doesn't go through the liver and is thus not liver toxic. It's important to differentiate these new products from the old methyl testosterone.
Oral testosterone undecanoate (T.U.) is taken twice daily, in doses ranging from 100 to 200 mg per capsule. Patients typically take two capsules twice a day, amounting to 400, 600, or 800 mg daily. These numbers are higher than the weekly doses of injectable testosterone because oral forms have lower bioavailability. The medication must be taken with food to ensure proper absorption through the lymphatic system, bypassing the liver.
The advantages of oral T.U. over other testosterone forms include a better safety profile, the ability to titrate doses easily, and a lower risk of side effects like blood pressure increases. The absorption mechanism is unique, involving a phytosterol ester that helps the testosterone absorb through the lymphatic system. This means it bypasses the liver, avoiding liver toxicity issues.
Regarding food intake, studies show that low, medium, and high-fat meals result in similar absorption rates. So, while a substantial meal may aid absorption, it's not necessary to be overly specific about the fat content.
Clinical data show that oral T.U. effectively raises testosterone levels. In studies, the average serum testosterone levels reached therapeutic ranges, with peaks within 3 to 5 hours of dosing and declining thereafter. This twice-daily dosing can be customized to better mimic the natural circadian rhythm of testosterone production, potentially benefiting patients by aligning with their daily energy needs.
An interesting aspect of this medication is its effect on sex hormone-binding globulin (SHBG) levels. Unlike other forms of testosterone, oral T.U. lowers SHBG, which can increase the proportion of free, biologically active testosterone. This can be particularly beneficial for patients with high SHBG levels, who may have symptoms of low testosterone despite normal total levels.
Regarding pituitary hormones like LH and FSH, oral T.U. seems to have a less suppressive effect compared to other testosterone forms, which could mean a lesser impact on fertility. Ongoing studies are investigating the long-term effects on sperm production and overall fertility.
Nelson Vergel: Dr. Sun, a question about food: Do we need a specific amount of fat in the food?
Dr. Sun: Good question. The studies suggest that low, medium, and high-fat diets result in similar testosterone absorption. While you don't need to count macros, I recommend taking it with something substantial for best results.
The effectiveness data shows that most patients achieve therapeutic testosterone levels, with some variability. The pharmacokinetics indicate a peak at around 3 to 5 hours post-dose, with levels tapering off by about 10 hours. This supports a twice-daily dosing regimen, which can be customized to align with a patient's daily routine and energy needs. For example, many patients take their second dose after lunch, which helps maintain energy levels into the evening and aligns with their natural circadian rhythm. This dosing strategy can also help regulate sleep patterns by avoiding elevated testosterone levels late at night.
Regarding safety, oral T.U. shows a lower incidence of adverse effects compared to injectable forms, particularly concerning high blood pressure and polycythemia (increased red blood cell count). The risk of liver toxicity is also minimal due to the drug's absorption method. Some patients report improvements in cholesterol and triglyceride levels, aligning with the broader health benefits of addressing low testosterone as part of metabolic syndrome management.
As for the titration guide, patients typically start at 200 mg twice daily, with adjustments based on serum testosterone levels and clinical response. Many patients eventually require higher doses, around 400 mg twice daily, to maintain optimal levels. I often start patients at this higher dose to achieve a more immediate therapeutic effect and assess safety and efficacy from the outset.
Nelson Vergel: Thanks, Dr. Sun. It's refreshing to hear from a clinician actively prescribing and adapting treatments based on patient needs. It's clear that customizing treatment protocols is crucial, as every patient is different. Can you discuss the availability and access to Kyzatrex, given the challenges with insurance coverage?
Dr. Sun: Sure. Kyzatrex has taken a different approach by opting for a direct cash pay model, bypassing insurance. This simplifies access and reduces paperwork for both patients and physicians. It also eliminates the delays associated with insurance authorizations. The average price is about $160 per bottle, which is a one-month supply. While this is more expensive than generic testosterone cypionate, it offers a more convenient and lower-risk option for many patients. For those who may need to donate blood frequently or take additional medications due to side effects from injections, the overall cost may be comparable.
Nelson Vergel: What kind of patients do you typically prescribe Kyzatrex to? Are there specific scenarios where it works best?
Dr. Sun: Kyzatrex is suitable for a variety of patients, including those who've experienced side effects from injectable testosterone, such as high blood pressure or polycythemia. It's also a good option for younger men who may still want to preserve fertility, as it has a less suppressive effect on LH and FSH. Additionally, it's beneficial for first-time testosterone users who may be needle-averse or looking for a less invasive option.
Nelson Vergel: Thank you for the comprehensive overview. It's clear that Kyzatrex offers a viable alternative to traditional testosterone therapies, with unique benefits. The focus on minimizing side effects and preserving natural hormone production is particularly interesting. We'll be sure to keep our audience updated on the latest developments and data as they become available.
Dr. Sun: Absolutely. It's been a pleasure discussing this topic. The landscape of testosterone therapy is evolving, and it's important to stay informed about the latest options and research. I'm happy to share my experiences and insights, and I look forward to future discussions, especially on topics like fertility and other emerging treatments. Thank you for having me, and I hope to join you again soon.
For more information: Oral Testosterone Replacement - KYZATREX® (testosterone undecanoate)
Dr Andrew Sun's Clinic: Andrew Y. Sun, MD | Urology Partners
Related video: Interview with Shalin Shah, CEO of Marius Pharmaceuticals, on Kyzatrex: An Oral Testosterone Treatment
