Shifting the Testosterone Treatment Paradigm with Oral Testosterone (Kyzatrex)

Again you heard it here first!

Nelson's domain the one and only!

Very informative webinar on the use of the newer oral TU formulations.

Testosterone therapy has long been dominated by injectable and topical formulations, but the landscape is evolving. This webinar explores how oral testosterone is redefining treatment protocols, offering a convenient and effective alternative. With recent clinical insights and real-world data, we’ll discuss why practitioners should reconsider their approach to testosterone replacement therapy (TRT).




What You’ll Learn:

• The clinical data on oral testosterone therapy and its impact on patient outcomes

• Key considerations for prescribing oral testosterone, including patient selection and monitoring

• Practical strategies for integrating oral testosterone into clinical practice

Briefing Document: The Shifting Paradigm of Testosterone Treatment with Oral Testosterone (Kyzatrex)​

This briefing document summarizes key themes and important facts regarding the evolving landscape of Testosterone Replacement Therapy (TRT), specifically focusing on the emergence and perceived benefits of oral testosterone formulations like Kyzatrex. The information is drawn from excerpts of discussions on the Excel Male TRT Forum, specifically a thread titled "Shifting the Testosterone Treatment Paradigm with Oral Testosterone (Kyzatrex)."

I. Main Themes:​

• Oral Testosterone as a Paradigm Shift: The central theme is the redefinition of TRT protocols through the introduction and increasing acceptance of oral testosterone formulations. Historically, injectable and topical methods have dominated, but oral options are presented as "redefining treatment protocols" and offering a "convenient and effective alternative."
• Emphasis on Clinical Insights and Real-World Data: The forum highlights the importance of understanding "clinical data on oral testosterone therapy and its impact on patient outcomes" to inform prescribing practices. There's an implicit need for practitioners to adapt and "reconsider their approach to testosterone replacement therapy."
• Practical Integration into Clinical Practice: A significant focus is placed on the practical application of oral testosterone, including "Key considerations for prescribing oral testosterone, including patient selection and monitoring," and "Practical strategies for integrating oral testosterone into clinical practice."
• Advocacy for Specific Testing Methods: The forum emphasizes the superiority of Equilibrium Dialysis for testing free testosterone, indicating a preference for precise and reliable diagnostic methods in managing TRT.
• Prominent Figures and Information Sharing: Dr. Andrew Sun is mentioned as a key figure associated with the "breakfast/lunch dosing schedule" for oral testosterone, suggesting expertise and specific protocols being discussed and promoted within the community.

Frequently Asked Questions about Oral Testosterone (Kyzatrex)​

What is Kyzatrex and how is it changing testosterone replacement therapy (TRT)?​

Kyzatrex is a newer oral formulation of testosterone (specifically, testosterone undecanoate, or TU) that is significantly evolving the landscape of Testosterone Replacement Therapy (TRT). Traditionally, TRT has been dominated by injectable and topical applications. Kyzatrex and other oral TU formulations offer a convenient and effective alternative, potentially redefining treatment protocols and making TRT more accessible and manageable for patients.

What are the key benefits of using oral testosterone like Kyzatrex compared to other forms of TRT?​

The primary benefit highlighted is convenience. Oral formulations offer an easier, non-invasive method of administering testosterone compared to injections or messy topical gels. This can significantly improve patient adherence to treatment and overall quality of life. The sources also imply that these newer oral formulations are backed by recent clinical insights and real-world data, suggesting effectiveness.

What are the important considerations for medical practitioners when prescribing oral testosterone?​

When prescribing oral testosterone, practitioners need to consider several key factors. These include appropriate patient selection, as not all patients may be suitable candidates for oral formulations. Ongoing monitoring is also crucial to ensure effectiveness and safety. Additionally, practitioners need to develop practical strategies for seamlessly integrating oral testosterone into their existing clinical practices.

Why is Dr. Andrew Sun mentioned in relation to oral testosterone?​

Dr. Andrew Sun is recognized as the "man behind the breakfast/lunch dosing schedule" for oral testosterone. This suggests he played a significant role in developing or popularizing a specific dosing regimen for these oral formulations, likely optimizing their efficacy and absorption based on meal times. His personal data is also referenced, indicating his involvement in research or practical application of this therapy.

What is the importance of "Equilibrium Dialysis" in the context of testosterone testing?​

"Equilibrium Dialysis" is emphasized as the preferred method for testing free testosterone. This indicates that it is considered the most accurate or reliable method for determining the biologically active form of testosterone in the body, which is crucial for effective diagnosis and monitoring of hypogonadism and TRT.

What is the primary focus of the ExcelMale TRT Forum regarding oral testosterone?​

The ExcelMale TRT Forum is actively promoting and discussing the adoption of oral testosterone, particularly Kyzatrex, as a significant advancement in TRT. They aim to inform practitioners and patients about its clinical data, benefits, and practical integration into treatment plans. The repeated mention of "Shifting the Testosterone Treatment Paradigm" underscores their belief in its transformative potential.

Are there other oral testosterone medications similar to Kyzatrex mentioned?​

Yes, in addition to Kyzatrex, other oral testosterone undecanoate (TU) formulations are mentioned, specifically Jatenzo and Tlando. This indicates that Kyzatrex is part of a broader class of newer oral TRT options.

What is "hypogonadism" and how does oral testosterone relate to it?​

Hypogonadism is a medical condition characterized by a deficiency in testosterone production. Oral testosterone formulations like Kyzatrex are designed to treat hypogonadism by supplementing the body's testosterone levels, thereby alleviating symptoms associated with low testosterone.

 

Thread 'EMPOWER PHARMACY - Personalizing Testosterone Therapy: Exploring Oral Solutions (Kyzatrex)'

Apr 13, 2025

It was inevitable.....you knew this was coming LOL!

As always Nelson's house is where it's at!

Testosterone Undecanoate (Kyzatrex®) Capsules

Choose Empower Pharmacy for compounded Kyzatrex capsules. The leading accredited 503A and FDA-registered 503B compounding pharmacy.

www.empowerpharmacy.com

Go big or go home we say!

Kyzatrex Webinar with Dr. Mohit Khera [April 2025]

Join our free webinar on April 10 2025, at 6:30 PM CST with Dr. Mohit Khera board-certified urologist, as we explore testosterone therapy.

www.empowerpharmacy.com

Hosted by Dr. Mohit Khera, a board-certified urologist and leading expert in testosterone optimization.

Empower is thrilled to host a free educational webinar on KYZATREX®, an FDA-approved oral testosterone treatment designed for men with low testosterone. It’s been shown to be up...

• madman
• oral-t; kyzatrex; empower; hypogonadism
• Replies: 15
• Forum: Compounding Pharmacy Product Reviews

• 

 

Thread 'Testosterone and Men's Hormone Health'

Jul 28, 2024

Dr. Jared Pelo interviews our advisor Andrew Y. Sun on men's hormone health and the nuances of testosterone replacement. This video goes into types of testosterone replacement and the positive benefits of utilizing this medical treatment.




Do you have these questions?

- What are the signs of low testosterone in men?
- How can I naturally increase my testosterone levels?
- What foods boost testosterone production?
- How does exercise affect testosterone levels?
- What are the benefits and risks of testosterone replacement therapy...

• madman
• hypogonadism; testosterone;trt; men's health
• Replies: 12
• Forum: Testosterone and Men's Health Articles

 

Thread 'CDC STANDARDIZED TOTAL T and ESTRADIOL ASSAYS and soon to be FREE TESTOSTERONE!'

Jan 5, 2019

How the CDC Clinical Standardization Programs Are Improving Hormone Tests - AACC.org

WHAT PROGRESS HAS CDC MADE WITH STANDARDIZING TOTAL TESTOSTERONE AND ESTRADIOL TESTS?



Since HoSt began in 2010, CDC has had more than 350 participants in 15 countries. Participants have shown measurable improvements for both total testosterone (TT) and estradiol (E2). Specifically, the among-laboratory bias has decreased from 16.5% in 2007 to 2.8% in 2017 for TT and from 54.8% in 2012 to 13.9% in 2017 for E2. Not only has bias improved, but data...

• madman
• Replies: 78
• Forum: Blood Test Discussion

• 

 

Thread 'Updates in testosterone therapy - Oral T combination Therapy'

Apr 28, 2025

* Sun explains how oral testosterone formulations—thanks to their short-acting pharmacokinetics—can preserve some endogenous testosterone production, unlike traditional injections that often completely suppress it.


* He details how he customizes treatment plans by blending oral testosterone with agents like Clomiphene to boost hormonal levels without fully shutting down the body's own system, offering a more physiologically balanced solution for men who may want children in the future.


* Later, they delve into combination therapy strategies, including using oral...

• madman
• hypogonadism; oral t/kyzatrex; trt; fertility/hpta
• Replies: 7
• Forum: Testosterone and Men's Health Articles

 

Thread 'Low Testosterone - Signs, Symptoms, and Treatments'

May 15, 2025

​

Dr. Andrew Sun, Fellowship-Trained Men's Health Urologist in Dallas, Texas, appears as a guest on The New Health to discuss Low Testosterone.

• madman
• hypogonadism; t-therapy; mens health
• Replies: 1
• Forum: Testosterone and Men's Health Articles

 

Thread 'Rethinking Oral TRT with KYZATREX®'

Jun 25, 2025

Modern patients want simple, effective treatment options.

KYZATREX® offers oral testosterone therapy with proven efficacy—and none of the mess, pain, or liver strain of older options.

.Join Dr. John Mulhall for a deep dive into the science and patient selection for KYZATREX®.




John P. Mulhall (Andrologist/Urologist)

• madman
• hypogonadism; oral t-therapy; kyzatrex®
• Replies: 11
• Forum: Testosterone and Men's Health Articles

 

Why does it cause such an extreme Elevation in DHEA Levels ??

 

Why does it cause such an extreme Elevation in DHEA Levels?

You would mean DHT.

This would be due to the activity of 5-alpha reductase in the GI tract.

The enzyme 5AR converts T to DHT.

* Oral TU is absorbed through intestinal lymphatics, bypassing complete first-pass hepatic metabolism. The presence of 5α-reductase in the GI tract leads to significant conversion to DHT, resulting in elevated serum DHT concentrations and an increased DHT/testosterone ratio.

https://www.sciencedirect.com/science/article/abs/pii/S0022356524308845

Because oral administration of TU results in the appearance of TU (and the metabolite 5-dihydrotestosterone undecanoate; DHTU) in lymph of thoracic duct-cannulated rats (Coert et al., 1975; Noguchi et al., 1985) and humans (for whom a thoracic duct cannula was inserted after neck dissection surgery; Horst et al., 1976), the androgenic activity of orally administered TU is generally attributed to T (and 5 -dihydrotestosterone; DHT) formed during the systemic metabolic elimination of TU, which escaped the presystemic first-pass effect due to intestinal lymphatic absorption and transport (Coert et al., 1975; Horst et al., 1976).




Absorption into Lymph after Oral TU Administration

TU and DHTU were observed in thoracic lymph after oral administration of TU to postprandial lymph duct-cannulated dogs, consistent with previous reports in rats (Coert et al., 1975; Noguchi et al., 1985) and humans (Horst et al., 1976). The profile of TU transport in lymph was essentially the same after oral administration of either the Andriol or Andriol Testocaps formulations (Fig. 2, B and E). Although of minor qualitative importance in terms of the mass transported, the profile of lymphatic TU transport was different compared with that observed for TG and DHTU transport. For example, although the maximum rate of lymphatic TU transport occurred 1 to 2 h postdosing, the maximal rate of transport of TG and DHTU occurred 2 to 3 h postdosing (Fig. 2, A and C). Furthermore, the rate of lymphatic TU transport declined rapidly after reaching its maximal transport rate, whereas the rate of TG and DHTU transport declined more gradually (Fig. 2, A–C). These profiles provide possible in- sight into the disposition of TU (and DHTU) within the gastrointestinal tract and enterocyte before absorption into lymph. For example, because TU is metabolized within the intestinal lumen and gut wall (Coert et al., 1975; Horst et al., 1976), which is the basis for the high serum concentrations of T and DHT observed in portal blood in the present study (Fig. 3), the change in the relative rates of TG and TU transport after the 1- to 2-h postdosing period likely reflects the reduction in the available mass of TU within the enterocyte for incorporation into chylomicrons. If a limiting factor in the kinetics of TU lymph transport was rapid hydrolysis within the intestinal lumen, then the observation of the prolonged transport of DHTU in concert with TG transport suggests that DHTU (formed by 5 -reductase metabolism of TU) may have a longer residence time within the enterocyte lipid- processing microdomains which could arise from either differences in the metabolic stability or enterocyte-based processing mechanisms for DHTU and TU.

Post in thread 'Should You Apply Testosterone Gel or Cream on Your Testicles for Best Absorption?'

Nov 18, 2018

where you have no hair follicle... most hairless area (shaven ballsack doesnt count for some reason)..
shoulders, forearms and scrotum are most androgenic (a lot of dht conversion)

Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels

Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue due to homeo

academic.oup.com

Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels (2017)
Ronald S. Swerdloff, Robert E. Dudley, Stephanie T. Page, Christina Wang, and Wael A. Salameh


Skin

Skin possesses all of the requisite steroidogenic capabilities to ensure local homeostatic control of...

• madman

Serum DHT levels are dependent upon the concentration of serum T achieved with TRT and the expression of normal levels of functional SRD5A in tissues. In adult eugonadal men, serum DHT levels are about one-tenth that of total serum T concentrations. As would be expected, the pattern of rise in DHT generally tracks with the increase in T, but the magnitude of change is substantially less. Differences in circulating DHT in response to various routes of T and prodrug (e.g., T esters) administration have been reported. In some cases, this can result in supraphysiologic DHT concentrations, thus leading to an important clinical question: What are the potential health effects of supraphysiological serum DHT concentrations in the setting of androgen therapy (e.g., TRT)?

To assess the clinical significance of modest elevations in serum DHT and DHT/T ratio observed with some delivery systems of TRT, we performed a comprehensive review of the published literature to identify relevant data. We examined not only studies in which elevated DHT was documented, but also those where 5AR-Is were used to suppress DHT production. Where appropriate, we have also included data from salient animal studies, although the focus of our analyses is principally on human data. In the case of some currently available TRT preparations, no pertinent published DHT data were available, and thus they are not included in this review. This points to a weakness in some studies of TRT or SRD5A inhibition, namely, the absence of data on circulating DHT levels. A notable case in this regard is the Prostate Cancer Prevention Trial (1), which evaluated the effects of 5AR-I treatment but did not directly measure serum DHT in the men treated with finasteride. Instead, serum 5α-androstane-3α, 17β-diol glucuronide, a distal metabolite of DHT, was used as a surrogate measure of intraprostatic DHT (5).




Oral TU preparations

An oral form of T replacement therapy that utilizes TU in an oil formulation was originally developed in the 1970s (253). Although never approved as a TRT in the United States, it remains on the market in over 80 countries across the world. A unique aspect of TU is its absorption exclusively via the intestinal lymphatics whereupon T is liberated via the action of nonspecific esterases (142). The typical dose for this product ranges from 80 to 200 mg/d of TU, which is roughly equivalent to 50 to 125 mg/d of T. A major disadvantage of this TU formulation is that the serum T response tends to be relatively low, as evidenced by mean T levels below the eugonadal range or only sporadically within normal limits (253, 254). In addition, this formulation must be administered with food containing some fat to ensure adequate bioavailability. Serum T, DHT, and DHT/T ratios observed after administration of this oral TU formulation in hypogonadal men are summarized in Table 4 (46, 75, 255,–257). In four studies in which sufficient data were reported, the average DHT/T ratios in response to therapeutic doses of oral TU ranged from 0.34 to 0.52. These DHT/T ratios are generally higher than ratios reported for most T replacement products and may reflect, in part, use of an immunoassay for analyzing DHT concentrations (68). Long-term exposure of hypogonadal men to oral TU, with the resultant elevations in the DHT/T ratios, has not resulted in toxicity, particularly related to the prostate gland. Gooren has provided the most comprehensive chronic safety summary for oral TU (75). Thirty-five hypogonadal men (aged 15 to 62 years) were administered oral TU (80 to 200 mg/d) for 10 years. Mean DHT concentrations (measured by RIA) increased modestly above the upper normal limit of 73 ng/dL (2.1 nmol/L) to about 96 ng/dL (3.31 nmol/L) over the period that the men were followed. The DHT/T ratio averaged 0.54 over the 10-year period compared with a reference range of 0.08 to 0.125. Despite these higher serum DHT and DHT:T ratios, long-term exposure to oral TU was not associated with any adverse effects on prostate as assessed by digital rectal exam, urine flow studies, and PSA. None of the subjects in the study developed prostate cancer.

Newer formulations of oral TU for TRT are in development. One such formulation (CLR-610) for which clinical data has been published contains TU in a self-emulsifying drug delivery system (258). Inherent in this formulation are excipients that foster the solubility and bioavailability of TU even when taken in a fasted state. Nonetheless, optimal TU absorption occurs when administered with food containing a typical level of fat. The pharmacokinetics of CLR-610 have been evaluated in trials reported by Yin et al. (68). After 28 days of oral TU administration at a dose of 316 mg TU, BID (equivalent to 200 mg T, BID), the average serum DHT levels increased from a baseline of 21 to 110 ng/dL (0.7 to 3.8 nmol/L), and the serum DHT/T ratio increased from 0.09 to approximately 0.3. The DHT and DHT/T ratio reference range reported by Yin et al. was approximately 14 to 77 ng/dL (0.5 to 2.7 nmol/L) and 0.04 to 0.11, respectively, as measured by LC-MS/MS.

Why oral TU tends to increase DHT more than parenteral forms of TU probably relates to several factors associated with the absorption of TU. As noted previously, TU enters the circulation only by intestinal lymphatic absorption. In the enterocyte, TU can be hydrolyzed to T by nonspecific esterases whereupon it can be further metabolized to DHT by 5α-reductase. DHT formed in intestinal tissue is rapidly metabolized to inactive glucuronides in gut or, if absorbed into the portal circulation, in liver tissue (6, 46) and thus contributes appreciably little, if any, to the circulating DHT pool. But TU can also be converted by enterocytic 5α-reductase to dihydrotestosterone undecanoate (DHTU), which then may be absorbed lymphatically. Action by nonspecific esterases on DHTU yields DHT, and it is this pathway that probably accounts for the modest elevations in DHT observed in response to oral TU preparations (142). Transient high concentrations of TU and DHTU occur after oral TU, and these may also impact circulating DHT (68). However, the impact of this must be considered small given modest increases in DHT after oral TU at a time of robust levels of TU and DHTU. Notably, TU and DHTU do not effectively bind to the AR due to an absence of a hydroxyl group at the C-17 position on T and steric hindrance created by the presence of the undecanyl group at this same position (21). Furthermore, TU and DHTU are rapidly metabolized and do not accumulate in the circulation after oral TU (68), nor are they sequestered in tissue (259).

 

Thread 'KYZATREX® - A NEW ORAL TESTOSTERONE & Why It's Better Than Injections'

Today at 5:52 PM

Show notes:

(0:00) Intro
(1:01) The 13-year FDA journey and breaking stigmas
(4:09) Why it’s different from other oral testosterone
(6:12) Mimicking the body’s natural testosterone rhythm
(9:10) Estrogen balance, side effects, and fertility concerns
(13:51) Testosterone’s role in women’s health
(16:56) Free vs total testosterone and SHBG reduction
(24:08) Testosterone vs weight loss drugs
(29:55) Who should be cautious with testosterone therapy
(35:46) What counts as low...

• madman
• hypogonadism; oral-t/kyzarex; mens health
• Replies: 3
• Forum: Testosterone and Men's Health Articles