Breaking New Ground in Men's Health: Oral Testosterone (Kyzatrex)

madman · Feb 6, 2025

In this episode, host McCall McPherson discusses a breakthrough in testosterone therapy with Shalin Shah, CEO of Marius Pharmaceuticals. They explore the development and benefits of Kyzatrex, a new oral testosterone replacement therapy. Shalin shares his journey into the testosterone space and highlights the importance of testosterone for overall health. They address the prevalence of low testosterone, its symptoms, and the limitations of traditional therapies. Kyzatrex offers a safer, more effective alternative with stable hormone levels and fewer side effects. The episode emphasizes the need for increased awareness and research in testosterone health.

madman · Feb 6, 2025

Thread 'Rethinking Testosterone: Oral Testosterone Modern Hormone Therapy'

Jan 23, 2025

Join Dr. Jared Pelo and Shalin Shah for an in-depth discussion about revolutionizing testosterone therapy. Shah, with his extensive background in healthcare investment and drug development, shares insights about Kyzatrex, an innovative oral testosterone medication, and discusses why testosterone has been misunderstood in medicine.

Learn about:

* Why testosterone was historically vilified and how recent research is changing perspectives

* The groundbreaking Traverse Study and its implications for cardiovascular...

molonlabedoc · Feb 7, 2025

How does this differ from Jetenzo?

madman · Feb 7, 2025

molonlabedoc said:
How does this differ from Jetenzo?

Nothing worth fretting over!

All of the oral T formulations use testosterone undecanoate in castor oil and the PKs are similar.

Other than the older oral TU Andriol which was dosed 2-3 times daily all of the newer oral TU formulations (Jatenzo, Tlando and Kyzatrex) are dosed twice daily (am/pm) which will result in 2 daily peaks/troughs.

Starting dose and strength of capsules differ between formulations.

The older oral TU Andriol had to be taken with a high fat meal to improve absorption/bioavailability whereas the newer oral TU formulations (Jatenzo, Tlando and Kyzatrex) can be taken with a normal meal.

Minor differences in some of the excipients between the formulations.

Something worth mentioning here mind you all of the newer oral TU formulations if dosed properly with a meal would allow one to achieve a healthy/high peak TT and more importantly FT level.

* Unique to Kyzatrex is a TU formulation of phytosterols contained in a softgel capsule with the intent of maximizing lymphatic absorption and minimizing liver toxicity.48

file:///C:/Users/bumpy/Downloads/DHPS-383130-safety-aspects-and-rational-use-of-testosterone-undecanoate-%20(5).pdf

Oral Testosterone Undecanoate Formulations

Andriol

History and Development

In the 1970s, when it was found that the esterification of testosterone allowed for its intestinal lymphatic absorption via chylomicrons, oral TT became a possibility.25 The first oral TU formulation has been marketed for use outside the United State as Andriol, and is available in more than 80 countries around the world.26

Efficacy

Initial studies of Andriol showed a modest rise in plasma testosterone levels and a substantial rise in dihydrotestosterone when compared with placebo and non-esterified oral testosterone, which established efficacy of the formulation as early as 1975.27,28 Additional randomized controlled trials confirmed improvement in quality of life scores as compared with placebo.29,30 Few adverse events were found in the trials, and those that did were considered minor, such as headache and gastrointestinal upset.26,29

Dosing

Dosing of Andriol is simple, with 40 and 80 mg capsules available and a starting dose of 120–160 mg divided into a twice-daily administration.31

Adverse Effects

Despite initial positive results with Andriol, there were three major concerns with the drug. First, serum testosterone levels vary widely throughout the day and despite reaching the normal range within hours following ingestion, serum testosterone rapidly falls back to the hypogonadal range.27,28,32 As a result, the average serum testosterone level may not be within the physiologic range of normal for the majority of men using the drug.33 Second, the bioavailability of Andriol has been shown to be highly impacted by a patient’s dietary habits. Similar lipophilic formulations of drugs have been shown to have enhanced absorption and bioavailability with food.34 Taking the drug after an overnight fast led to serum concentrations of testosterone and its downstream metabolites below the limit of quantification.26 Additionally, meals with a higher fat content led to elevated serum concentrations of testosterone and its downstream metabolites.35 Though these studies used smalls ample sizes and heterogenous study techniques, these results suggest that unintentionally elevated serum testosterone levels may occur in patients who consume more fat. Overall, the necessity of combining Andriol with a meal may impact patient satisfaction and compliance with the drug, which make it a less ideal choice for TT. Lastly, Andriol undergoes metabolism in the liver, which decreases the bioavailability of the drug.36 As a consequence, higher doses may be required for the action of the drug and it is important to note that this formulation may not be a suitable choice for those with liver disease. Despite concern, data has not shown change in liver function while on Andriol,36 though caution should still be applied when prescribing this drug for those with comorbid liver conditions.

Jatenzo

History and Development

In 2019, the United States Food and Drug Administration approved the first oral testosterone ester prodrug – Jatenzo.37 As with all exogenous androgens, Jatenzo exerts its effect through suppressing FSH/LH and therefore endogenous testosterone function and production.38 Jatenzo was developed with a unique self-emulsifying drug delivery system (SEDDS) consisting of hydrophilic and lipophilic components that facilitate intestinal lymphatic absorption. In addition,this formulation allows absorption with a typical meal (15–45 g fat) as opposed to high fat-containing meals required for prior formulations.39 Jatenzo quickly leads to a serum testosterone concentration peak at two to four hours after ingestion, which slowly decreases to sub-physiologic levels near hour 9, thus requiring twice-daily dosing.36,40

Efficacy

Long-term and short-term phase III clinical trials confirmed efficacy of the oral TU formulation, as 84 and 87%,respectively, of patients enrolled in the trials became eugonadal during treatment as compared to topical testosterone gel.36,40 This oral formulation of TT also significantly improved subjective quality of life and metabolic parameters across varied diets, suggesting that Jatenzo absorption is not dependent on consumption of fats and therefore could be beneficial for diverse patient populations.36

Dosing

Dosing of Jatenzo is straightforward, with the usual adult dosage ranging from 158–396 mg.41 Based on the results of the clinical trials, the recommended starting dose is 237 mg taken as one 158 mg capsule twice daily.40 Dosing can be up or down titrated based on the individual’s testosterone concentration drawn 6 hours after morning dose.41

Adverse Effects

In initial trials of this oral TU formulation, adverse effects were consistent with other TT including polycythemia as well asa small, but statistically significant, increase in systolic blood pressure when compared to topical testosterone.36 Other side effects included transient and minor gastrointestinal concerns such as nausea, diarrhea, and burping, which may be associated with any oral medication. Importantly, and unlike other oral TU, Jatenzo partially avoids liver metabolism and has not been associated with liver toxicity. It has also not been shown to elevate markers of prostate cancer such as PSA and prostate volume specifically when compared with topical testosterone formulations. Overall, these adverse effects indicate the need for routine monitoring of hematocrit and blood pressure, as is consistent with AUA guidelines for any patient receiving TT.

Tlando

History and Development

In 2014, a clinical trial comparing a novel TU formulation against topical testosterone gel began, and in 2022 this product, marketed as Tlando, was approved for use in the United States. This capsule contains 112.5 mg of TU in a unique predigested triglyceride lipid formulation.42 Consistent with all other TU products, this lipid emulsification is designed to optimize absorption of TU through the intestinal lymphatic system. This formulation was hypothesized to avoid dose titration when used as twice daily TT.

Efficacy

Initial trials showed efficacy of Tlando in returning the majority of participants to a eugonadal testosterone range.42 Further, early results of a small, single-arm, open-label multicenter study (NCT03242590) presented at the Annual Meeting of the Endocrine Society showed that dose titration of Tlando did not alter pharmacokinetics.43 That same year, presented at the American Urologic Association, results of a year-long, open-label, active-controlled multicenter study confirmed that dose titration had an insignificant impact on pharmacokinetics.44 A final, open-label, multicenter study (NCT03242590) confirmed these results and suggested that adverse effects related to elevated serum testosterone, thus requiring dose titration, can be avoided with the new formulation.42

Dosing

Dosing of Tlando is straight forward, with a starting dose of 225 mg daily split into two equal doses of one, 112.5 mg pill, twice daily.45

Adverse Effects

Adverse effects of Tlando are similar to other forms of TT, including a minor increase in hematocrit and PSA.42 A unique adverse effect of the early trials, an elevated blood prolactin, was the most commonly reported side effect.42 Minor increases in systolic blood pressure along with elevated hematocrit were found to be clinically significant in a small, but significant number of patients.46 Further studies into long-term effects, both positive and negative, will be needed to elucidate side effects of this formulation.

Kyzatrex

History and Development

The most recently approved TT is Kyzatrex, which received FDA approval in August 2022.47 Unique to Kyzatrex is a TU formulation of phytosterols contained in a softgel capsule with the intent of maximizing lymphatic absorption and minimizing liver toxicity.48

Efficacy

A phase III open-label, active-controlled clinical trial (NCT03198728) showed efficacy of the formulation, with 88% (95% CI 82–93) of male patients with an average serum testosterone level in the eugonadal range, which led to FDA approval.49

Dosing

Dosing of Kyzatrex is more variable than Tlando, with 100 mg, 150 mg, and 200 mg softgel capsules available and a recommended starting dose of 200 mg orally twice daily with food, followed by titration up or down based on serum testosterone concentration 7 days after starting treatment.49

Adverse Effects

The initial study was extended (NCT04467697) to further assess blood pressure effects of the formulation. The results of this safety study showed small but significant increases in systolic blood pressure, especially in men already taking antihypertensive therapy and those with type 2 diabetes, which follows trends previously reported with TT.50 Importantly,the clinical relevance of these small increases in systolic blood pressure is unclear, and requires further long-term studies.Other adverse effects of Kyzatrex include rare instances of headache, GI upset, elevated hemoglobin and PSA, anxiety, and peripheral edema.49

Post in thread 'FDA Approves Oral Testosterone Replacement Therapy Kyzatrex'

Aug 11, 2022

Systemlord said:
I'm only seeing this new oral T option hitting a peak at 600 ng/dL and I'm hitting as high as 715-650 ng/dL after 4 hours and 981 ng/dL at 2 hours.

@madman Can you explain why after the second or evening dosage the peak and trough levels are a little higher than after the first dosage?

The only thing I can come up with is a higher metabolism during the daylight hours versus the night time.

Look over the Cmax (Mean/SD) for KYZATREX® in Table 5.

The peak/trough between the two doses (AM/PM) in Figure 2. is nothing to brag about.

The peak between the two doses...

Post in thread 'Kyzatrex or Jatenzo'

Feb 21, 2024

charile12 said:
Good day all. I've been on testosterone cypionate almost 7 years. I inject anywhere from 100 to 120 mg in total divided 2 times a week. Am 47.
I'm feeling good consistently for years now.

Looks like my insurance cover oral testosterone.
I did read some threads on here, I see system Lord is doing well on jatenzo. I'm looking to see if I should switch to oral.

I'm just looking for people's experience on either of these two orals
Kyzatrex or Jatenzo. Any clear winner?
Thank you.

There is no clear winner.

You have 3 options when it comes to oral T (Jatenzo, Tlando, and...

Post in thread 'KYZATREX (oral testosterone undecanoate) now available in all states across the US'

Jun 14, 2024

Possible dose titration (Jatenzo or Kyzatrex) needs to be kept in mind when it comes to the cost as not everyone will fare well or hit a high enough T level with the starting doses.

A phase III, single-arm, 6-month trial of a wide-dose range oral TU (Kyzatrex) product

Abstract Background Oral testosterone undecanoate (TU) formulations may provide effective, safe, and easily titratable testosterone replacement therapy. Objective Demonstrate efficacy and safety of a novel oral TU formulation. Design An open-label, single-arm, multi-center trial treated...

www.excelmale.com

Dose and impact of baseline characteristics.

The distribution of final doses is provided in Figure 3. The logistic regression analysis of the impact of baseline characteristics on final dose demonstrated that body weight and diabetic status were positively associated...

madman · 2025-03-07T23:47:56-0600

Thread 'How Affordable Oral TRT Could Save Your Manhood'

Yesterday at 11:46 PM

Shalin Shah and his company's product have totally changed my opinion about TRT. I had a ton of misconceptions about testosterone replacement therapy. My thoughts have changed, and I think you'll find this episode very revealing.

In this episode we cover:

-The difference between oral and injectable testosterone

-Dispelling the myths about TRT

-Determining the minimum effective dose for TRT dosage

-The synergistic effects