Oral TRT Products: Jatenzo, Tlando, Kyzatrex, & DiTest

Testosterone Replacement Therapy: A Narrative Review with a Focus on New Oral Formulations (2022)
Salman Z Bhat and Adrian S Dobs

FDA approved.webp



Male hypogonadism affects 10–30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with specific benefits and limitations. These replacements include gels, patches, and short- and long-acting injectables. JATENZO® (oral testosterone undecanoate; Clarus Therapeutics Inc., Northbrook, IL, US) is the first oral formulation of testosterone approved by the US Food and Drug Administration. TLANDO® (oral testosterone undecanoate; Lipocine Inc., Salt Lake City, UT, US), another oral testosterone formulation, has also recently been approved by the US Food and Drug Administration. Based on unique chemistry using a self-emulsifying drug delivery system and lymphatic absorption, JATENZO and TLANDO address some of the limitations of other dosing routes while providing a safe option without evidence of liver dysfunction. This review discusses various testosterone treatment options, focusing on the role and pharmacokinetics of the new oral formulations.



Depending on how it is defined, male hypogonadism affects between 10% and 30% of the male population and is often under-recognized and under-treated.1–3 It is defined by low sex hormone levels (<12 nmol/L or <300 ng/dL), which can affect multiple organ systems, resulting in symptoms and signs of testosterone deficiency (Table 1) and significantly reducing the quality of life.4–6 Several studies have shown that patients with hypogonadism have an increased all-cause and cardiovascular mortality rate.7,8 It is also associated with an increased risk of obesity and type 2 diabetes mellitus.9–11

Treatment with testosterone replacement therapy (TRT) is strongly indicated for the structural causes of hypogonadism (i.e. damage to the testes, pituitary gland, or hypothalamus). Positive impacts of TRT on hypogonadism include improvements in erectile dysfunction, libido, lean body mass, and bone mineral density.12–14 Beneficial effects on mood, cognition, and metabolic parameters (body fat, insulin resistance, and lipid levels) have also been noted.15,16 However, the impact of TRT on all-cause and cardiovascular mortality is controversial and not well defined.17,18 The benefit of TRT in age-related decline in testosterone is also not well established, and the US Food and Drug Administration (FDA) has discouraged treatment in this scenario.19

The US Endocrine Society and the European Academy of Andrology recommend testosterone levels in the hypogonadal range (<12 nmol/L or <300 ng/dL) in three or more morning samples sent for biochemical analysis and symptomatic assessment (Table 1) before the diagnosis of hypogonadism.20,21 From the outset of diagnosis, the patient and healthcare provider should discuss and agree on the goals of therapy. Clinical conditions affecting testosterone-binding proteins (sex hormone binding globulin and albumin) result in falsely elevated/low total testosterone values, and the measurement of free testosterone is recommended in such scenarios (Table 2).20,21 Guidelines do not recommend universal screening for hypogonadism;20,21 however, physicians should remain more vigilant with patients at risk of hypogonadism (e.g. patients with HIV, pituitary disease or on chronic opioid therapy).

Caution is advised when treating age-related physiologic decreases in testosterone levels with TRT, as clinical data for the risks and benefits of TRT in the older patient population is not clear.
The Testosterone Trials (The Testosterone Trials in Older Men; ClinicalTrials.gov identifier: NCT00799617) are a prospective analysis of TRT use in older men that showed moderate benefits with regard to sexual function (measured using the Psychosexual Daily Questionnaire-Q4 [PDQ-Q4] score for sexual activity, the Derogatis Inventory of Sexual Function-Men-II score for sexual desire and the International Index of Erectile Function [IIEF] score for erectile function) and a minor but significant effect on some aspects of mood symptoms (measured using the Positive and Negative Affect Score and the Patient Health Questionnaire-9 depression score).22 However, no significant benefit in primary outcomes of physical function and vitality was noted though.22 The trials were not powered to analyze risk.22 Ageing patients display a physiologic decline in testosterone levels, and treating these men in non-specific clinical scenarios (e.g. fatigue, decreased endurance) may do more harm than good.19 The Endocrine Society guidelines thus recommend an individualized treatment approach with a detailed discussion of risks in this patient population, even those patients with a hypogonadal biochemical and symptom profile.2






*Therapeutic options for male hypogonadism


*Challenges of the existing formulations




*Oral testosterone formulations: A new therapeutic avenue


The oral delivery route is the most common delivery system for the majority of medications. It solves many limitations of the alternative routes discussed above. Studies of other diseases have shown oral therapy to be preferred by patients compared with other routes.31,32 Oral testosterone was not a therapeutic option in the early stages of testosterone drug development due to its metabolism in the gut and high first-pass metabolism in the liver, which resulted in subtherapeutic plasma levels.33 After 17 α-methylation was found to protect testosterone against hepatic metabolism, the 17-methyl-testosterone formulation had higher oral bioavailability and was approved by the FDA.34 However, the use of 17-methyl testosterone and other 17-α alkylated formulations is limited by the significant hepatotoxic effects noted in early case studies.35–37 The hepatotoxic effects include cholestasis, vascular injury (peliosis hepatis), transient hepatitis, and hepatic tumor formation.35–37 The mechanism of hepatic injury is unclear, but it likely involves ductal and hepatocyte growth stimulus.

TU is an esterified form of testosterone introduced in Europe in the 1970s and is available in both oral and injectable formulations. The esterification of the 17 β position coupled with an oleic acid vehicle increased lymphatic absorption in the gut, thus bypassing the first-pass metabolism in the liver. A major advantage of TU is the considerably lower liver toxicity compared with the 17-methylated products in prospective studies. TU is partially metabolized in the intestinal wall, absorbed through intestinal lymphatics, and converted primarily to 5-dihydro-testosterone.
Intake with high-fat-content meals was important to aid absorption and achieve physiologic bioavailability. Earlier studies reported a peak serum testosterone level 2 to 6 hours after dosing, with high inter-individual variability.38 An oleic acid vehicle was used in the initial formulation, which needed to be kept refrigerated to maintain stability. In the early 2000s, it was replaced with castor oil/propylene glycol, which had equal efficacy but a better room temperature shelf life of 3 years.39 Oral TU in the above formulation has been approved for use in Europe, but it is not approved by the FDA due to erratic absorption, unsteady physiologic testosterone levels, patient-reported lack of efficacy, and dependence on high dietary fat for absorption.40

There had been an extensive search for a new drug delivery system that could provide reliable concentrations of testosterone (a hydrophobic molecule) and not require intake with a high-fat-content meal, which could place an additional burden on therapy. The novel self-emulsifying drug delivery system (SEDDS) provided a breakthrough in achieving this.41 SEDDS consists of a surfactant with a high hydrophilic-lipophilic balance, a co-surfactant, and a carrier oil dissolving the hydrophobic drug, which can self-emulsify in the gastrointestinal tract.41 Self-emulsification increases the surface area and enhances drug absorption in the lipophobic environment (Figures 1–3).41


Newer testosterone formulations based on SEDDS bypass the need for high-fat-content meals. In 2019, JATENZO® (TU; Clarus Therapeutics Inc., Northbrook, IL, USA) was the first oral TRT approved by the FDA for use in primary and central hypogonadism caused by structural and genetic defects. Its use for age-related hypogonadism has not yet been approved. It is available in different dosing formulations (158 mg twice daily [BID]; 198 mg BID; 237 mg BID), which helps in titration. The recommended starting dose is 237 mg BID. It still needs to be taken with meals but without the requirement of high-fat content. A phase III trial (A Study of Oral Testosterone Undecanoate [TU] in Hypogonadal Men [inTUne]; ClinicalTrials.gov identifier: NCT02722278) comparing JATENZO to topical testosterone (patients receiving JATENZO: n=166; oral: topical assignment: 3:1) reported comparable efficacy in improving testosterone levels to eugonadal range (87%) (24-hour bioavailability; Figure 4).42 Seventy-two percent of patients treated with the oral formulations required up-titration of the dose, which was performed twice. The titration process used average testosterone concentrations derived from 24-hour pharmacokinetic data on days 21 and 56 of the trial (average of the Na F-EDTA testosterone levels at 0, 2, 4, 6, 9, and 12 hours after the am dose and 0, 2, 4, 6, 9 and 12 hours after the pm dose). The 24-hour data correlated very well with single-point testosterone concentrations (between hours 4 and 6 after oral TU administration), which is typically used in the outpatient setting. The testosterone levels achieved did not depend on the fat composition of meals.

JATENZO led to statistically significant improvement in sexual and mood symptoms (measured using the PDQ), comparable to topical TRT. Common side effects included gastrointestinal reactions (nausea, diarrhea), which occurred at significantly higher rates in the oral TRT group. Besides the previously defined class side effects, JATENZO has a small but significant increase in 24-hour average systolic blood pressure (JATENZO 4.9 ± 8.7 mmHg versus topical testosterone 0.2 ± 9.4 mmHg; p=0.0013) along with an increase in low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol. No increase in the incidence of liver dysfunction was noted. JATENZO was also found to significantly improve quality of life (measured by improvement in the 36-Item Short Form Survey and PDQ, p<0.0001), bone mineral density (mean increase in bone mineral density over 180 and 365 days in the spine was 0.013 ± 0.035 and 0.018 ± 0.042 g/cm2, respectively, and in the hip 0.006 ± 0.019 and 0.012 ± 0.023 g/cm2, respectively; p<0.0001) and lean body mass (an increase of 2.87 ± 2.73 and 3.15 ± 2.69 kg at 180 and 365 days, respectively, (p<0.0001) compared with baseline.43

TLANDO® (Lipocine Inc., Salt Lake City, UT, USA), another oral formulation of TU using SEDDS, has recently been approved by the FDA for the treatment of male hypogonadism.44 As this formulation does not require dose titration, patients do not need to have regular blood work, making use and follow-up easier. A 52-week open-label multicentre study in men diagnosed with hypogonadism comparing a titratable regimen of TLANDO (n=210) to topical testosterone (n=105) showed similar average and maximum concentrations of testosterone, with an equal proportion of study participants achieving eugonadal levels.45 Beneficial effects were noted in sexual and mental domain patient-reported outcomes.46 The effect of titration on the achieved testosterone levels was minimal. Subsequently, an open-label, single-arm trial studying the efficacy and safety of a fixed dose of TLANDO (225 mg BID) treatment for 24 days on hypogonadal men (N=95) demonstrated steady 24-hour average serum testosterone levels in 80% of patients without the need for titration (Dosing validation study of oral testosterone undecanoate [TU, LPCN 1021]. [DV]; ClinicalTrials.gov identifier: NCT03242590).47 Figure 5 shows the 24-hour bioavailability of TLANDO. The effect of fat content in food was studied in a smaller cohort and did not show any difference in bioavailability between different diets. Another trial evaluating a fixed dose regimen of 150 mg thrice daily did not meet efficacy targets.48 Intake with meals is necessary for absorption; however, no requirement of fat content is necessary.


A single-arm study to evaluate the effect of TLANDO on different blood pressure parameters (participants who received at least 1 dose of the study drug: n=138) noted a mean increase of 3.8 mmHg (95% confidence interval: 1.7–6.0) and 1.2 mmHg (95% confidence interval: 0.3–2.1) in 24-hour ambulatory systolic and diastolic blood pressure, respectively.49 The mean increase was higher in patients with baseline hypertension compared with non-hypertensive subjects (4.5 mmHg/1.5 mmHg versus 3.2 mmHg/0.9 mmHg, respectively).49 The increase in ambulatory blood pressure was highest in the quartile with the highest hematocrit increase, promoting the hypothesis of hematocrit-induced hypertension.

Interestingly, a prodrug of TLANDO, LPCN 1144 (Lipocine, Inc., Salt Lake City, UT, USA) was also noted to decrease the hepatic fat content in a subset of patients from the ambulatory blood pressure trial, and its benefit in treating non-alcoholic fatty liver disease, which is associated with male hypogonadism, is currently being studied.50

Another novel oral TU option (KYZATREX™; Marius Pharmaceuticals, Raleigh, NC, USA) that uses a phytosterol carrier vehicle is being studied in the RE-TUne study (Efficacy and safety of oral testosterone undecanoate in hypogonadal men; ClinicalTrials.gov identifier: NCT03198728), but results have not been published yet.51





*The hypertensive effect: Route or class specific?

Previous trials using TRT for hypogonadism did not address the cardiovascular risk with adequate power. The analysis of cardiovascular outcomes from epidemiological, prescription data, and retrospective studies has shown conflicting results. Among others, the results of the prospective Testosterone in Older Men with Mobility Limitations (TOM: Testosterone in Older Men With Sarcopenia; ClinicalTrials.gov identifier: NCT00240981) trial52 and the retrospective study of hypogonadal men who underwent coronary angiography, subsequently treated with TRT,17 among others, demonstrated a significant increase in major adverse cardiovascular events. As a result, there is an increased focus on evaluating these outcomes in future TRT formulations.


Most of the side effects reported for oral TRT represent a class effect, including headache, elevated prostate-specific antigen, increased hematocrit, and a change in serum lipids. A significant elevation in blood pressure in the oral TRT arm compared with the control arm merits further discussion.
Both TLANDO and JATENZO and a new self-injectable medication, testosterone enanthate (XYOSTED®; Antares Pharma, Ewing, NJ, USA) have shown elevations in ambulatory blood pressure compared with the treatment arm. JATENZO is also associated with increased low-density lipoprotein cholesterol levels, whereas TLANDO is not.


Hypertension is a major cardiovascular risk factor, and, given the unclear association of TRT with increased cardiovascular disease, worsening blood pressure may be detrimental to the long-term use of TRT. Possible mechanisms suggested include a rise in hematocrit and sodium and water retention. It is unclear why oral TRT might be the only therapy with this side effect. Erythrocytosis is a class-wide effect of TRT. TRT stimulates erythropoietin release, increases iron absorption by decreasing hepcidin levels, and directly enhances erythropoiesis.53 An increase in hematocrit, seen with both JATENZO and TLANDO, has been strongly associated with an increase in blood pressure.54,55 Elevation in blood pressure from TRT is likely to be a class-specific side effect, which was not demonstrated with other routes as earlier studies had not specifically looked at outcomes of blood pressure with ambulatory monitoring techniques, which are more sensitive for capturing blood pressure changes.




Conclusion

Oral TRT is an important advance in testosterone replacement options for patients requiring treatment. Oral replacement provides ease of administration with reliable serum levels and adequate efficacy (Table 4). The FDA-approved oral TU formulations discussed above provide reliable testosterone levels when compared with topical TRT, without the need for ingestion with a high-fat-content meal and with no additional incidence of hepatotoxicity. The clinical benefit has also been demonstrated in these studies, although it has not been their primary outcome. Patient satisfaction is similar to other forms of TRT, compared with previous oral TRT medications that were often associated with a decreased efficacy by patients.56 Long-term safety and efficacy data are not available, and direct comparisons to other forms of TRT have not been performed yet. The oral formulations have shown small but significant elevations in blood pressure during ambulatory blood pressure monitoring, which is likely a class-specific effect. With the appropriate monitoring of serum testosterone levels, blood pressure, and complete blood count, oral testosterone is another option for men requiring testosterone treatment. ❑
 
I have tried Jatenzo on a few occasions, but never got to seven days.
Have you tried Jatenzo after no injections for a couple of weeks?

Stacking both may be causing your problems. I felt bad on Jatenzo 2, 3 and 4th week and I’ll bet it has to do with the cypionate leaving my system and my T levels dropping back into the normal ranges.
 
Have you tried Jatenzo after no injections for a couple of weeks?

Stacking both may be causing your problems. I felt bad on Jatenzo 2, 3 and 4th week and I’ll bet it has to do with the cypionate leaving my system and my T levels dropping back into the normal ranges.
Guilty as charged. My feedback is virtually useless as I barely got past a few days.
 
No miracles, LOL. But I'll also add this. I didn't have any problems in the bedroom with my wife, but my urologist asked me one day if I'd like to be like 17 again, and I said I was open to trying it. He gave me 5mg daily of Cialis, and wow, what a difference. I was really surprised by it. I'm also highly interested in the other benefits it offers. if you haven't read about it, see this thread - it's one of the best ones I've seen here:


Already on that and unfortunately dealing with pretty severe Peyronies.
 
I thought orals were less ideal as caused higher stress on liver esp as take MUCH MUCH larger doses per week. is that false? or was more so with woman oral hormones?

of course risks and benefits to every form so would be interested if anyone has noted elevated liver enzymes etc.
 
I thought orals were less ideal as caused higher stress on liver esp as take MUCH MUCH larger doses per week. is that false? or was more so with woman oral hormones?
Only true for the old methyl testosterone. Oral testosterone undecanoate does not stress the liver.

In contrast to some other oral testosterone forms, testosterone undecanoate enters the bloodstream via the lymphatic system rather than the portal vein. This is important because substances that enter the bloodstream through the portal vein go directly to the liver.

This "first pass" through the liver can be harmful for certain substances, as it may lead to liver damage. Some oral anabolic steroids, for example, have been linked to liver toxicity due to this first-pass metabolism. However, because testosterone undecanoate is absorbed by the lymphatic system, it bypasses this first pass through the liver, thereby reducing the potential for liver toxicity.

This is a prime example of how the method of drug administration can greatly impact its safety profile. Nonetheless, while oral testosterone undecanoate does not have the same risk for liver toxicity as some other oral steroids, it's essential to use it responsibly and under the guidance of a healthcare provider due to other potential side effects.
 
I thought orals were less ideal as caused higher stress on liver esp as take MUCH MUCH larger doses per week. is that false? or was more so with woman oral hormones?

of course risks and benefits to every form so would be interested if anyone has noted elevated liver enzymes etc.

 
cool, def would be interesting to see anecdotal liver enzymes before and after. would be interesting if would have increase risk of lymphatic cancer growths vs other test.

pretty poor absorption obv, so would be interesting how much untouched passes through stool or if ends up being broken down in the gut. or simply destroyed

also INTERESTING HELPS liver.... but also curious if the other subset got an INCREASE in hepatic fat content, and this subset was just guys who lost weight on trt.
"terestingly, a prodrug of TLANDO, LPCN 1144 (Lipocine, Inc., Salt Lake City, UT, USA) was also noted to decrease the hepatic fat content in a subset of patients from the ambulatory blood pressure trial, and its benefit in treating non-alcoholic fatty liver disease, which is associated with male hypogonadism, is currently being studied."

also a small note said oral test tends to increase hemocrit more "and needs to be studied why this oral form does this" I thought all trt is likely to cause this, some more than others..

not hating, but skeptical hippo eyes just because dose is sooo high, like with most things takes awhile to figure out all the side effects. but also may just be a great TRT option..

but ya, waiting with bated breath how folks labs change esp with liver/hemocrit. not much easier than pills! no cross contamination, no embolism/infections, and presumably less HPTA shut down as short acting... neat stuff
 

Comparison of Jatenzo, Kyzatrex, and Tlando​

Overview​

Jatenzo, Kyzatrex, and Tlando are all oral testosterone undecanoate (TU) formulations used for testosterone replacement therapy (TRT) in men with hypogonadism. These medications offer an alternative to traditional intramuscular injections and topical gels, providing a more convenient oral administration route.

Mechanism of Action​

All three drugs work by replacing the testosterone that is not being produced naturally by the body. They are metabolized through the lymphatic system, which helps avoid liver toxicity, a significant issue with earlier oral testosterone formulations.

Dosage and Administration​

  • Jatenzo: The recommended starting dose is 237 mg taken orally twice daily with food. The dosage can be adjusted based on serum testosterone levels, with a range from 158 mg to 396 mg twice daily.
  • Kyzatrex: The starting dose is 200 mg taken orally twice daily with food. The dosage can be adjusted based on serum testosterone levels, with a range from 100 mg once daily to 400 mg twice daily.
  • Tlando: The recommended dose is 225 mg taken orally twice daily with food. Unlike Jatenzo and Kyzatrex, Tlando does not require dose adjustments.

Efficacy​

  • Jatenzo: In clinical trials, Jatenzo achieved eugonadal testosterone levels in 87% of participants. It has shown significant improvements in sexual and mood symptoms, bone mineral density, and lean body mass.
  • Kyzatrex: In a phase III trial, 96.1% of participants achieved normal testosterone levels after 90 days. The drug was well-tolerated, with no serious adverse events reported.
  • Tlando: Approximately 80% of subjects attained testosterone levels within the eugonadal range in clinical studies. Tlando has also shown beneficial effects on sexual and mood symptoms.

Side Effects​

  • Jatenzo: Common side effects include gastrointestinal reactions (nausea, diarrhea) and a small but significant increase in systolic blood pressure (4.9 mmHg).
  • Kyzatrex: The most notable side effect is a slight increase in systolic blood pressure (1.7 mmHg). No serious adverse events were observed in the study.
  • Tlando: Similar to Jatenzo, Tlando has been associated with increases in blood pressure and prolactin levels. The mean increase in systolic blood pressure was 3.8 mmHg.

Cost and Insurance​

The cost and insurance coverage for these medications can vary. All three drugs are prescription-only and may present a barrier for some patients due to cost and lack of insurance coverage.

Conclusion​

Jatenzo, Kyzatrex, and Tlando offer effective and convenient oral options for testosterone replacement therapy. Each has its own dosing regimen and side effect profile, but all have shown to be effective in achieving normal testosterone levels in hypogonadal men. The choice between these medications may depend on individual patient needs, side effect tolerance, and cost considerations.


Citations:
[1] Jatenzo vs Tlando Comparison - Drugs.com
[2] Oral Drugs Offer New Option for Testosterone Replacement
[3] A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product
[4] Oral Testosterone Replacement Therapy: What’s Available and What Took so Long? - American Urological Association
[5] Kyzatrex vs Tlando Comparison - Drugs.com
[6] https://www.goodrx.com/classes/androgens/oral-testosterone-vs-injection
[7] https://www.liebertpub.com/doi/full/10.1089/andro.2022.0011
[8] Testosterone oral agents (JATENZO, TLANDO) - www.westernhealth.com
[9] Testosterone Replacement Therapy: A Narrative Review with a Focus on New Oral Formulations
[10] A Review of Testosterone Therapy Options for Men
[11] https://www.touchendocrinology.com/...review-with-a-focus-on-new-oral-formulations/
[12] https://liebertpub.com/doi/full/10.1089/andro.2021.0025
[13] Testosterone Update on Oral Products
 
where is the cheapest place I can get Kyzatrex with no insurance?

One average $149 and even then keep in mind this is for the starting dose 200 mg 2x/day.

Some men will not achieve high enough levels on such and may need to titrate up to 300 or 400 mg dosed twice daily (600-800 mg/day)!

Look over post #48!




post #6/48
 
One average $149 and even then keep in mind this is for the starting dose 200 mg 2x/day.

Some men will not achieve high enough levels on such and may need to titrate up to 300 or 400 mg dosed twice daily (600-800 mg/day)!

Look over post #48!




post #6/48

 
I have heard Kyzatrex can reverse testicular atrophy to some extent versus injectables, is this correct?

Is it reasonable to expect similar free and total T numbers on Kyzatrex as e.g. EOD test cyp injections or is there an upper limit?
 
I have heard Kyzatrex can reverse testicular atrophy to some extent versus injectables, is this correct?

Is it reasonable to expect similar free and total T numbers on Kyzatrex as e.g. EOD test cyp injections or is there an upper limit?

I have heard Kyzatrex can reverse testicular atrophy to some extent versus injectables, is this correct?


Kyzatrex (oral TU) dosed 2x daily will result in less suppression of the hpta than injectable esterified T due to the PK which will result in 2 shorter-lived daily peaks with longer trough times between doses.

The trough levels achieved (sub-physiologic) are nothing to brag about!

From the most recent pilot study I uploaded in (post #8).

High-dosed oral TU (Kyzatrex 400 mg) BID, LH/FSH while lower were maintained at non-zero levels, minimal impact on hematocrit!

None of the patients reported testicular atrophy.

Even then need to keep in mind the only way for an individual to truly know how much testicular shrinkage occurred would be to have testicular volume measured using a prader orchidometer or ultrasonography pre/post TRT.

You would never truly know playing the guessing game!





*At a mean follow up time of 6 months, patients demonstrated a significant increase in TT (263 to 798 ng/dL), drop in SHBG (32.4 to 17.83 nmol/L), and increase in calculated fT (7.24 to 26.74 ng/dL). FSH and LH, while lower, were maintained at non-zero levels (FSH from 5.7 to 2.9 mIU/mL and LH from 3.3 to 1.9 mIU/mL). Estradiol modestly increased (20.5 to 24.7 pg/mL) while hematocrit did not significantly increase (44.9% to 47.4%). No patients reported testicular atrophy or were initiated on aromatase inhibitors. One patient had a hematocrit rise above 52% (53.2%) and was reduced to 300 mg BID.


* Initiating oral TU therapy with Kyzatrex at 400 mg BID is safe and effective in achieving therapeutic serum testosterone levels. The high dose was well-tolerated and resulted in substantial symptom improvement, high patient satisfaction, and adherence. These findings support considering a higher starting dose for hypogonadal men considering oral TU therapy.






Also keep in mind there are only 2 other studies on oral TU/gonadotropins using Jatenzo and one was short-term (2 weeks) which had minimal impact while the other study was much longer (16 weeks) and showed a strong suppression of LH/FSH.

Suppression of LH 75%!

Again the most recent pilot study using high-dosed oral TU (Kyzatrex 400 mg) BID mean follow-up time 6 months LH/FSH while lower were maintained at non-zero levels.

Other than nasal T gel (Natesto) any form of exogenous whether T pellets, oral esterified T (Jatenzo), transdermal gels/creams, injectable esterified T when used in therapeutic doses to treat low testosterone will have a strong impact on suppression on the hpta.

Formulation/PKs, dosing protocol/minimum effective doses needed to raise T levels in order to achieve a healthy FT level in order to provide relief/improvement of symptoms will results in suppression of the hpta.

Long and medium-acting injectable esterified TU/TC/TE/mixed will have the strongest impact.

Even short-acting injectable esterified TP can still have a strong suppressive effect on the hpta

As I stated in a previous thread when using daily short-acting TP the T levels achieved peak vs trough let alone the time period over those 24 hrs T levels are elevated whether mid-range/high/absurdly high will still result in a strong suppression of the hpta.

Top it off there are many injecting daily TP hitting very high/absurdly high peaks let alone healthy troughs.

Next would be oral TU (Jatenzo) and transdermals.

Nasal T gel would be the least suppressive due to the PK/dosing protocol.

Any formulation that has a strong suppressive effect on the hpta will result in testicular shrinkage and negative effect on fertility/spermatogenesis.

As you would know the addition of an LH mimetic (hCG) will allow one to maintain some degree of intra-testicular testosterone (ITT) which will helps minimize/prevent testicular atrophy and maintain fertility while using exogenous T.

The addition of hCG + rFSH would be more effective!








Is it reasonable to expect similar free and total T numbers on Kyzatrex as e.g. EOD test cyp injections or is there an upper limit?


Looking over any of the studies done using oral TU one can easily achieve a high-end and in some cases very high peak TT/FT level let alone a small % of outliers have been able to hit an absurdly high peak!


*The percentage of patients who received KYZATREX and had testosterone Cmax threshold less than or equal to 1200 ng/dL, between 1440 and 2000 ng/dL, and greater than 2000 ng/dL at the final PK visit were 88%, 4%, and 0%, respectively.


*The percentage of patients who received JATENZO and had Cmax less than or equal to 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL at the final PK visit were 83%, 3%, and 3%, respectively.


* The percentage of patients who received TLANDO and had a T Cmax threshold less than or equal to 1620 ng/dL, between 1944 ng/dL and 2700 ng/dL, and greater than 2700 ng/dL at the PK visit were 82%, 5%, and 0%, respectively.



Keep in mind dose used/absorption of T is what matters as the bioavailability is very low compared to injections.

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


Even then one could never achieve the TT/FT (peak/trough) let alone steady-state levels that one can easily attain when using injectable T due to the dose of T/bioavailability/PK.

As I stated in a previous thread:

Keep in mind if your goal is to take advantage of the anabolic properties of T then injectables are where it's at as one can easily attain high/absurdly high trough FT levels.

When it comes to reaping the full anabolic benefits not only is having supra-physiological levels of FT steady-state 24/7 important but also how high you drive up FT levels.

When it comes to packing on size/mass/strength T is king!


Would definitely look into giving oral TU (Kyzatrex) a go if you are interested!
 

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