Controversies with Testosterone Replacement Therapy: Lecture by Dr Khera

[madman]

As usual Nelson's Excel is where it's at!

Mohit Khera, MD, MBA, MPH, Professor of Urology, F Brantley Scott Chair in Urology, Medical Director of the Laboratory for Andrology Research, Medical Director for the Scott Department of Urology Baylor College of Medicine.

 

[madman]

 

[madman]

* If you treat men with testosterone there are 5 controversies you need to be aware of!

 

[madman]

 

[madman]

Is Oral T (testosterone undecanoate) Safe and Effective for Men With Low Testosterone?

Is Oral Testosterone Safe and Effective for Men With Low Testosterone? Ask a sexpert! Dr. Omer Raheem answers this question in the latest episode of this video series.

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Oral testosterone. Who's on it?

Who here is on some form of oral. jatenzo/Kyzatrex? What has it done for you? What are your numbers? Has RBC increases been as much as a problem for you on the orals? How is your liver tests? Thank you

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Prostate Risk and Monitoring During TRT

ABSTRACT Men with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial. Several studies including four larger randomized trials — the Testosterone Trials...

www.excelmale.com

Is testosterone therapy dangerous for the prostate

The EAU Guidelines Office will provide a state-of-the-art update on male hypogonadism and testosterone replacement therapy. This recording will be of great educational value for urologists as internationally-known experts will focus on the controversial and challenging areas of this rapidly...

www.excelmale.com

Male hypogonadism: Testosterone therapy is not dangerous

The EAU Guidelines Office will provide a state-of-the-art update on male hypogonadism and testosterone replacement therapy. This recording will be of great educational value for urologists as internationally-known experts will focus on the controversial and challenging areas of this rapidly...

www.excelmale.com

Is testosterone therapy dangerous for the heart

The EAU Guidelines Office will provide a state-of-the-art update on male hypogonadism and testosterone replacement therapy. This recording will be of great educational value for urologists as internationally-known experts will focus on the controversial and challenging areas of this rapidly...

www.excelmale.com

Testosterone Therapy and Erythrocytosis - the most common dose-limiting effect of testosterone therapy

https://www.thebloodproject.com/cases-archive/testosterone-therapy-and-erythrocytosis-2/ Introduction Androgens play a crucial role in the development and maintenance of: Male reproductive and sexual functions Body composition Erythropoiesis Muscle and bone health Cognitive function...

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Management of Male Fertility in Hypogonadal Patients on TRT

Abstract Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind...

www.excelmale.com

 

[granger]

-if testosterone makes you go bald u have higher risk of Cardio events..DHT levels matter.
-MANY people get elevated liver enzymes on TRT. the new oral form monitored guys for how long? 3 months? is that long enough to really get a picture?
-dosing matters
-if TRT elevates your markers for cardiovascular events then yes it will increase likelyhood of events. OR are they saying huge swaths of cardio science is incorrect? (sure some things in flux, cholesterol, aPOB but they are interconnected)
-castrated animals live the longest

when you see such presentations one has to wonder has he ever done research that he gave to a drug company? if so, having seen it FIRST HAND Drs esp when drive fancy cars will skew results.

when say NO hepatotoxicity yet take 100s of mg a day? where does that extra T go? not the liver? So many gaping holes in this new ORAL T i promise it will be a matter of time before its proven incorrect.. would be interesting if folks on teh net who take oral T if have switched modalities or started T and post blood results including liver enzymes.... everyones TRT dr always gets live enzymes checked to, right?

 

[madman]

-if testosterone makes you go bald u have higher risk of Cardio events..DHT levels matter.
-MANY people get elevated liver enzymes on TRT. the new oral form monitored guys for how long? 3 months? is that long enough to really get a picture?
-dosing matters
-if TRT elevates your markers for cardiovascular events then yes it will increase likelyhood of events. OR are they saying huge swaths of cardio science is incorrect? (sure some things in flux, cholesterol, aPOB but they are interconnected)
-castrated animals live the longest

when you see such presentations one has to wonder has he ever done research that he gave to a drug company? if so, having seen it FIRST HAND Drs esp when drive fancy cars will skew results.

when say NO hepatotoxicity yet take 100s of mg a day? where does that extra T go? not the liver? So many gaping holes in this new ORAL T i promise it will be a matter of time before its proven incorrect.. would be interesting if folks on teh net who take oral T if have switched modalities or started T and post blood results including liver enzymes.... everyones TRT dr always gets live enzymes checked to, right?

So many gaping holes in this new ORAL T i promise it will be a matter of time before its proven incorrect..

-if testosterone makes you go bald u have higher risk of Cardio events..DHT levels matter.

-MANY people get elevated liver enzymes on TRT.


Out to lunch here!

Hope you understand that if one is genetically prone to MPB high DHT levels are not needed in order to accelerate such as it comes down to the sensitivity of the AR at the hair follicle to DHT.

Even then there are also other factors at play here.

Having a low FT level would make one more prone to CVD.

Healthy FT levels let alone T s metabolites estradiol and DHT are needed in order to reap full beneficial effects of testosterone.

Ts metabolites estradiol and DHT are needed in healthy amounts to experience the full spectrum of testosterones beneficial effects on (cardiovascular health, brain health, libido, erectile function, bone health, tendon health, immune system, lipids, and body composition).

Would not even waste my time fretting over liver health/lipids when it comes to oral TU!

You should be far more concerned with the use/abuse of the oral 17α-alkylated AAS such as stanozolol, oxandrolone, methyltestosterone, methandrostenolone, oxymetholone, and fluoxymesterone which are notorious for driving down HDL, increasing LDL, stressing the liver and hammering down SHBG.

The c-17 alpha-alkylated orals put a greater strain on the cardiovascular system and are also known to be liver-toxic when abused especially long-term!

17a-Methyltestosterone was the first oral to hit the market in the early 70s as it was used as a form of testosterone replacement and although it is still being manufactured in the US it is rarely prescribed due to its high potential for liver toxicity.


*The hepatotoxic side-effects are due to the alkyl group in the 17a position and have also been reported for other steroids with this configuration (Krüskemper and Noell 1967). Because of the side effects, methyltestosterone should no longer be used therapeutically for hypogonadism, in particular since effective alternatives are available (Nieschlag 1981). The German Endocrine Society declared methyltestosterone obsolete in 1981, and the German Federal Health Authority ruled that methyltestosterone should be withdrawn from the market (Anonymous 1988). In other countries, however, methyltestosterone is still in use, a practice which should be terminated.


Oral TU (Andriol) was also introduced to the market in the 70s and was the go to oral T for testosterone replacement as it is non-alkylated and was considered a safe non-hepatotoxic oral androgen for long term substitution in men suffering from hypogonadism.

It was on the market in Canada for decades.

It is still on the market in many countries and was the only oral T available in Canada up until recently as it was discontinued in 2018 and replaced with a generic oral TU.

The first oral formulation of testosterone Jatenzo was approved by the US FDA back in 2019.

Jatenzo was the first non-c17 alpha alkylated oral available on the US market.

Other formulations of oral TU such as Tlando and Kyzatrex were released in 2022.

Take home point here:

Oral TU - safe non-hepatotoxic oral androgen




*JATENZO is the first oral testosterone replacement therapy that's been approved by the FDA in over 40 years. The previous product, methyl testosterone, was known to cause hepatotoxicity and therefore is almost never used today. JATENZO is formulated as a self-emulsifying drug delivery system and avoids the first pass effect through the liver

*Effects of testosterone therapy (TTh) on lipid parameters are inconsistent and may depend on treatment duration, route of administration, and adherence. While in short-term studies, testosterone usually lowers HDL, long-term studies seem to increase HDL. Total cholesterol, LDL, and triglycerides are either reduced by TTh, or effects are neutral

*Testosterone modulates the function of different tissues (muscle, adipose, and bone) and cell types (epithelial, endothelial, and hematopoietic) and regulates the metabolism of lipids, carbohydrates, and proteins.

Testosterone is closely related to blood lipid metabolism. Long-term testosterone therapy improves the lipid profile by reducing total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels, and increasing high-density lipoprotein (HDL) cholesterol levels compared with baseline levels.

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

Abstract

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.




Essential Points

• Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis.

• The modest increases observed in serum DHT and in the DHT/T ratio observed after TRT are unlikely to be a cause of clinical concern, particularly when viewed in the context of changes observed in these parameters for currently marketed T-replacement products and those under development for which DHT data are available.

• While well-controlled, long-term studies designed to specifically examine the effects of androgen exposure on risk for prostate need to be conducted, the current clinical data base is relatively reassuring that circulating levels of androgens (or changes in such) apparently do not play as pivotal a role as once thought in the development of prostate disease.

• Robust epidemiologic or clinical trial evidence of a deleterious DHT effect on CVD is lacking. There is some evidence that DHT therapy in men with CVD may improve clinical status—a finding that needs confirmation. Data from a longitudinal data base of older normal (i.e., not hypogonadal) indicated an association between serum DHT and incident CV disease and mortality. Conversely, others have reported that higher DHT levels in older men were associated with decreased all-cause mortality and reduced ischemic heart disease mortality. Additional exploration in prospective, placebo-controlled intervention studies of TRT with CVD as the primary endpoint is needed to resolve the long-term effects of androgens on CVD risks.

• DHT does not play a substantive role in body composition compared to T under normal conditions. Thus, elevated levels of DHT in response to TRT are unlikely to appreciably impact lean or fat mass. Nonetheless, data from animals suggest a role for DHT in adipose tissue that inhibits biochemical pathways involved in lipid synthesis and promotes several transcripts associated with apoptosis of adipocytes. Whether these DHT-induced effects also occur in human adipose tissue remains an area for future study.

• There is very limited data available regarding DHT and effects on cognition. Further research is needed, particularly in light of animal data where DHT positively modified synaptic structure and significantly delayed cognitive impairment in a well-regarded animal model for Alzheimer’s disease.

• Recent data indicating that higher levels of DHT were inversely associated with insulin resistance and risk of diabetes merit further mechanistic investigation to understand whether this action is separate from that of T.

Routine laboratory measurements of liver function tests are presented in Table 1 as mean values ± SD, unless they were recorded as below a certain limit. No impairment of liver functions was observed, nor was there a tendency in any of the parameters towards higher/lower values.




Table 3 – Liver function tests in 33 men taking 80-200 mg oral testosterone undecanoate (TU)/day in a 120 month follow-up study. Of the eight men over 50 years of age at the start of the treatment, urine flow was also measured.Values are the mean + SD.

In conclusion, TU appears to be an oral androgen that served 33 hypogonadal over a period of 10 years satisfactorily in spite of low normal to subnormal testosterone levels. There is evidence, however, that restoration of sexual function in men does not require physiological levels of testosterone. There was no evidence of liver function disturbances, nor were there signs of acceleration of the development of BPH in these men. None of the patients had signs of a prostate tumor upon digital examination.

Androgen Physiology, Pharmacology, Use and Misuse - Endotext - NCBI Bookshelf

Oral Testosterone​

Finely milled testosterone (167, 641) or testosterone suspended in an oil vehicle (642, 643) have low oral bioavailability requiring high daily doses (200–400 mg) to maintain physiologic testosterone levels. Such a heavy androgen load causes prominent hepatic enzyme induction (644) without hepatotoxicity (645). Although effective in small studies (646), oral testosterone is not commercially available and little used. Sufficiently high oral testosterone doses (400-900 mg daily) also reduce serum SHBG (647) which may explain the concomitant acceleration of testosterone metabolism (167, 646, 648).

Oral Testosterone Undecanoate​

Oral testosterone undecanoate, a suspension of the ester in 40-mg oil-filled capsules, is administered as 160 to 240 mg in two or more doses per day (677). The hydrophobic, long aliphatic chain ester in a castor oil/propylene glycol laurate vehicle favors preferential absorption into chylomicrons entering the gastrointestinal lymphatics and largely bypassing hepatic first-pass metabolism (173). Oral testosterone undecanoate is not absorbed under fasting conditions but is taken up when ingested with food (678) containing a moderate amount (at least 19 gm) of fat (679). Although oral testosterone undecanoate produces a disproportionate increase in serum DHT which is unaffected by concomitant administration of an oral 5 α reductase inhibitor (680); such modest increases in circulating DHT would have no impact on prostate size (681) or apparent risk of prostate cancer (454, 682) presumably because DHT of extra-prostatic origin fails to increase intra-prostatic DHT concentrations (683). Its low oral bioavailability (684) and short duration of action requiring high and multiple daily doses of testosterone lead to only modest clinical efficacy compared with injectable testosterone esters (657, 685). Widely marketed, it may cause gastrointestinal intolerance but has otherwise well established safety (682). A new formulation of oral testosterone undecanoate was approved for US marketing in 2019 (686) over four decades after its introduction in Europe (687) to close the gap in the market for a safe non-hepatotoxic oral androgen. Its limitations in efficacy, notably its capricious bioavailability, make it a second choice (657), unless parenteral therapy is best avoided (e.g., bleeding disorders, anticoagulation) or a low dose, as for induction of male puberty, must be provided (688, 689) as a better option than the hepatotoxic alkylated androgen, oxandrolone (690).

Steriodal Androgens​

Most oral androgens are hepatotoxic 17α-alkylated androgens (methyltestosterone, fluoxymesterone, oxymetholone, oxandrolone, ethylestrenol, stanozolol, danazol, methandrostenolone, norethandrolone) making them unacceptable for long-term androgen replacement therapy. The 1-methyl androgen mesterolone is an orally active DHT analog that undergoes neither amplification by 5α reduction nor aromatization but it is free of hepatotoxicity. Mesterolone is not used for long-term androgen replacement due to the need for multiple daily dosing, its poorly defined pharmacology (691) and suboptimal efficacy at standard dose (570, 577). For historical reasons, the other marketed 1-methyl androgen methenolone is used almost exclusively in anemia due to marrow failure (692, 693) although it has no specific pharmacological advantage over testosterone or other androgens.

HEPATOTOXICITY​

Hepatotoxicity is a well-recognized but uncommon side effect of 17α-alkylated (340) whereas the occurrence of liver disorders in patients using non-17α alkylated androgens such as testosterone, nandrolone, and 1-methyl androgens (methenolone, mesterolone) are no more than by chance (341). This is consistent with the evidence of direct toxic effects on liver cells of alkylated but not non-alkylated androgens (758). The risk of 17α alkylated androgen-induced hepatotoxicity is unrelated to the indication for use, although association with certain underlying conditions may be related to intensity of diagnostic surveillance (341). It is possible, but unproven, that the risks are dose-dependent although relatively few cases are reported among women using low dose methyl-testosterone (759, 760) while clinical management of children using the alkylated androgen oxandrolone often omits liver function tests. However, even if the risks are dose-dependent, the therapeutic margin is narrow. By contrast, the rates of hepatotoxicity among androgen abusers who typically use supraphysiological, often massive, doses remain difficult to quantify due to underreporting of the extent of illicit usage and dosage but abnormal liver function tests are common in androgen abusers when checked incidentally as part of other health evaluation.

Biochemical hepatotoxicity may involve either a cholestatic or hepatic pattern and usually abates with cessation of steroid ingestion. Elevation of blood transaminases without gamma-glutamyl transferase may be attributable to rhabdomyolysis rather than to hepatotoxicity if confirmed by increased creatinine kinase (761). Major hepatic abnormalities are related to use of 17-alkylated androgens include peliosis hepatis (blood-filled cysts) (762) and hepatic rupture, adenoma, angiosarcoma (763, 764) and carcinoma; however, these risks do not apply to testosterone or other non alkylated androgens such as nandrolone or 1-methyl androgens. Prolonged use of 17α-alkylated androgens, if unavoidable, requires regular clinical examination together with biochemical monitoring of hepatic function, the latter not required for non-alkylated androgens. If biochemical abnormalities are detected, treatment with 17α-alkylated androgens should cease and safer androgens may be substituted without concern. Where structural lesions are suspected, radionuclide scan, ultrasonography, or abdominal computed tomography scan should precede hepatic biopsy during which severe bleeding may be provoked in peliosis hepatis. Because equally effective and safer alternatives exist, the hepatotoxic 17α-alkylated androgens should not be used for long-term androgen replacement therapy. By contrast, pharmacological androgen therapy often uses 17α alkylated androgens for historical reasons rather than the non-hepatotoxic alternatives. In these situations, the risk-benefit analysis needs to be judged according to the clinical circumstances.

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 Male hypogonadism affects 10–30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with...

www.excelmale.com

FDA-Approved Oral Testosterone: Jatenzo (Testosterone Undecanoate)

The U.S. Food and Drug Administration today approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or...

www.excelmale.com

 

[granger]

33 men is not much of a study IMO... 27 of them 80mg tablets, are 80mg available currently? or a the MUCH MUCH higher doses that are RX right now? ALOT of unknowns. are we really to believe ORAL LARGE DOSES are LESS harmful than injections of same compound that completely bypass the liver? how could this be? is having high testosterone for longer periods of time like injections allow THAT much worse for the liver? or perhaps the one study on lymphatic absorption we are giving WAY to much credit for being correct?

even at the VERY low dose of 80mg quote from the study on 33men 27 on only 80mg "However, there have been documented reports of gastrointestinal intolerance, increased hematocrit, increased hypertension, and decreased HDL cholesterol levels which changed when increasing dosage". so this is not zero, why did the doctor say NONE? what about triple that dose and more that is normally taken? this study also puts alot of emphasis on correcting blood markers with lowering dose and i dont think in the USA you can even get 80mg to start with nevermind taking less of them a day.

yes dht is very genetic(just like estrogen conversion), that being said, bald men have more heart attacks. this is known..Ive seen it with my own eyes, chances are majority of people you know who had a heart attack have male pattern baldness and even more with gys who lost it earlier it seems.. is it directly T? no, but having higher dht(which oral increases the most according to your study) makes you more prone to heart attacks so if raising your T you raise DHT you are more likely to have a cardiac event.. again, there is a reason bald men usually have more Test and are ALOT more likely to have a heart attack. IF oral test is causing a LARGER increase IN DHT as your study says I would bet that this will lead to higher and more severe cardiac events. again, time will make this more certain. but again INJECTIONS cause elevated liver enzymes too and def arent absorbed in the stomach.. that is to say there is no logic that oral test would be BETTER (esp when doses are SOOOO high) than injections from a liver enzyme point of view and infact likely much worse as other oral testosterone has been proven to be.. if its relative to serum T and time than folks should really consider lower less frequent doses of injectable T. ASSUMING that the factor is the multi troughs of low T per day thats making the difference.

remember we dont have SERIOUS science that confirms anything about lymphatic absorptions and appears to be hypothetical for the most part.

again, have you not talked to men on trt? do they not often have worsening liver function? why is this so common? by what mechanism can injections worsen liver and oral be even worse for liver but a high dose ester not be bad for the liver? just doesn't equate.. and i guess my issue is fancy DRs trying to sell something and despite what DECADES of research says they use the companies small data set or 1 small poorly done study (ie no control) to say something they more than likely know to be false but CAN say otherwise as have SOME literature to indicate as much..

they can say all the theories they want about oral but in reality they are taking HUGE doses, if not processed by the liver were is all that extra testosterone going? doesnt disappear and no sign of it showing up in feces is there? its pretty absorbable so I dont think folks are only absorbing 5% of the dosage, do you? any data on testing feces? or jus the 1 study from park? anyway, time of course will give us answers, im just very sceptical. would be interesting to talk to a dr who RX alot of oral T and see what types of blood markers they see change..(although great Drs its heard to get that type of info as they feel they are just guessing so they won't say anythingas unethical).

that is all to say, new forms are great, we just have to be honest about risks and what we ACTUALLY know and observe in post marketing data vs what drug company says or the fancy salesman DRs say.. i've just been around long enough to know that every "new" thing that has 0 side effects and all the benefits we usually find out that its not the case.

im all for TRT dont get me wrong, but there is little nuance in alot of what the Dr said which is disingenuous to put it mildly. yes MANY guys on any form of TRT can have improved liver function and cardiac health, but many people have much the opposite. many things at play, dosage, modality, but also BMI and changes in BMI from trt. that is to say a big if not majority of benefits of TRT come down to body comp and mental effects. There is no free lunch and everything has draw backs, to not address that or accept it is just silly. super high test is going to increase IGF and if you have high IGF chances are your not going to be 85+yo, thats ok for some people, but shouldnt be ignored.. i guess just get tired of clinics and fast talking Salesman tell half truths and downplay REAL risks and ignore decades of data because some DR gave his patients testosterone and made the loose 50lbs of fat and completely change lifestyle as men on TRT often do (or maintain there active lifestyles). Which of course makes it hard to compare apples to apples when BMI or body comp changes as that has a host of benefits unrelated to test itself.

anyway, as i said time will tell and i will be happy to hear of guys having better liver function on oral T and full symptom relief.. unfortunate very few clinics actually order liver panels

 

[granger]

on a side note.. they are already working on making a better form of oral test as to not cause the supraphysiologic increase in DHT(as thats not a good thing for health esp cardiac health) lol.. no ester, MUCH lower doses! An oral lipidic native testosterone formulation that is absorbed independent of food.

just keep in mind when they say "PART" is not absorbed in the stomach ie cause liver issues.. and if it raises testosterone in less than or around 1 hour chances are its MOSTLY getting absorbed in the stomach, just from logical/physical stand point. infact a pill can be stuck for up to 2 hours in your stomach... so just think about that when you take your oral T and you feel effects in 30-40min chances are you arent bypassing much of hepatic system.

 

[Nelson Vergel]

I have been taking Kyzatrex for three months. No liver issues.

 

[madman]

on a side note.. they are already working on making a better form of oral test as to not cause the supraphysiologic increase in DHT(as thats not a good thing for health esp cardiac health) lol.. no ester, MUCH lower doses! An oral lipidic native testosterone formulation that is absorbed independent of food.

just keep in mind when they say "PART" is not absorbed in the stomach ie cause liver issues.. and if it raises testosterone in less than or around 1 hour chances are its MOSTLY getting absorbed in the stomach, just from logical/physical stand point. infact a pill can be stuck for up to 2 hours in your stomach... so just think about that when you take your oral T and you feel effects in 30-40min chances are you arent bypassing much of hepatic system.

I will reply once the issues with the servers are fixed!

 

[madman]

33 men is not much of a study IMO... 27 of them 80mg tablets, are 80mg available currently? or a the MUCH MUCH higher doses that are RX right now? ALOT of unknowns. are we really to believe ORAL LARGE DOSES are LESS harmful than injections of same compound that completely bypass the liver? how could this be? is having high testosterone for longer periods of time like injections allow THAT much worse for the liver? or perhaps the one study on lymphatic absorption we are giving WAY to much credit for being correct?

even at the VERY low dose of 80mg quote from the study on 33men 27 on only 80mg "However, there have been documented reports of gastrointestinal intolerance, increased hematocrit, increased hypertension, and decreased HDL cholesterol levels which changed when increasing dosage". so this is not zero, why did the doctor say NONE? what about triple that dose and more that is normally taken? this study also puts alot of emphasis on correcting blood markers with lowering dose and i dont think in the USA you can even get 80mg to start with nevermind taking less of them a day.

yes dht is very genetic(just like estrogen conversion), that being said, bald men have more heart attacks. this is known..Ive seen it with my own eyes, chances are majority of people you know who had a heart attack have male pattern baldness and even more with gys who lost it earlier it seems.. is it directly T? no, but having higher dht(which oral increases the most according to your study) makes you more prone to heart attacks so if raising your T you raise DHT you are more likely to have a cardiac event.. again, there is a reason bald men usually have more Test and are ALOT more likely to have a heart attack. IF oral test is causing a LARGER increase IN DHT as your study says I would bet that this will lead to higher and more severe cardiac events. again, time will make this more certain. but again INJECTIONS cause elevated liver enzymes too and def arent absorbed in the stomach.. that is to say there is no logic that oral test would be BETTER (esp when doses are SOOOO high) than injections from a liver enzyme point of view and infact likely much worse as other oral testosterone has been proven to be.. if its relative to serum T and time than folks should really consider lower less frequent doses of injectable T. ASSUMING that the factor is the multi troughs of low T per day thats making the difference.

remember we dont have SERIOUS science that confirms anything about lymphatic absorptions and appears to be hypothetical for the most part.

again, have you not talked to men on trt? do they not often have worsening liver function? why is this so common? by what mechanism can injections worsen liver and oral be even worse for liver but a high dose ester not be bad for the liver? just doesn't equate.. and i guess my issue is fancy DRs trying to sell something and despite what DECADES of research says they use the companies small data set or 1 small poorly done study (ie no control) to say something they more than likely know to be false but CAN say otherwise as have SOME literature to indicate as much..

they can say all the theories they want about oral but in reality they are taking HUGE doses, if not processed by the liver were is all that extra testosterone going? doesnt disappear and no sign of it showing up in feces is there? its pretty absorbable so I dont think folks are only absorbing 5% of the dosage, do you? any data on testing feces? or jus the 1 study from park? anyway, time of course will give us answers, im just very sceptical. would be interesting to talk to a dr who RX alot of oral T and see what types of blood markers they see change..(although great Drs its heard to get that type of info as they feel they are just guessing so they won't say anythingas unethical).

that is all to say, new forms are great, we just have to be honest about risks and what we ACTUALLY know and observe in post marketing data vs what drug company says or the fancy salesman DRs say.. i've just been around long enough to know that every "new" thing that has 0 side effects and all the benefits we usually find out that its not the case.

im all for TRT dont get me wrong, but there is little nuance in alot of what the Dr said which is disingenuous to put it mildly. yes MANY guys on any form of TRT can have improved liver function and cardiac health, but many people have much the opposite. many things at play, dosage, modality, but also BMI and changes in BMI from trt. that is to say a big if not majority of benefits of TRT come down to body comp and mental effects. There is no free lunch and everything has draw backs, to not address that or accept it is just silly. super high test is going to increase IGF and if you have high IGF chances are your not going to be 85+yo, thats ok for some people, but shouldnt be ignored.. i guess just get tired of clinics and fast talking Salesman tell half truths and downplay REAL risks and ignore decades of data because some DR gave his patients testosterone and made the loose 50lbs of fat and completely change lifestyle as men on TRT often do (or maintain there active lifestyles). Which of course makes it hard to compare apples to apples when BMI or body comp changes as that has a host of benefits unrelated to test itself.

anyway, as i said time will tell and i will be happy to hear of guys having better liver function on oral T and full symptom relief.. unfortunate very few clinics actually order liver panels

Found a temporary way around this!

Oral TU - Safety/Efficacy

@granger

www.excelmale.com

 

[granger]

thank you for posting info!

i guess what im saying is no one is going into liver failure area.. i think we can agree, this is what is considered CLINICAL significance. what we do know is liver markers will change.

I have been taking Kyzatrex for three months. No liver issues.

let us know when you get your first bloods and if have pre trt other trt and current oral trt levels that would be cool to see liver markers and lipids!

anyway dht is not great for one whatever degree you feel it is cardiac DRs feel its bad so thats enough for me. oral TU is bad for DHT increase. i may be incorrect but DHT itself is harder on the liver, ie the higher it is typically same BMI will have worse liver function. what makes kidney stones more likely again in TRT patients? at the very least we know it increases DHT ad DHT is bad for liver (among other things) so by what magic does this TU bypass all these mostly accepted facts?


do we have fecal analysis of oral TU users? are we to assume testosterone that is VERY easily absorbed is 90% passed through the feces unchanged? or is it more likely it actually is processed by the liver? the TU is very absorbable and AGAIN how is it possible it kicks in within 30-40min when it doesn't even START to leave the stomach until 1-2 hrs? ie if serum raises before 1 hour its not bypassing stomach absorption. this is also why the levels go up and down so fast.. unless i am missing what they are saying about stomach absorption which may be highly likely..

why had previous attempts for TU fail? did they complete randomized trial yet? "I also agree that a randomized trial should be done; I would argue that it ought to be done pre-approval, not post-approval. I think cardiovascular clinical endpoints really do sway a clinician's practice habits..,?"FDA Panel: Two Thumbs Down for New Oral Testosterone Drugs

remember 80mg or 160mg is different than ~500mg a day..even if differnt formulas get same T level, what about the extra taxation on liver?


no cardiovascular risk the dr says.? "Around 5.9% of the overall group receiving Jatenzo treatment had to begin a new antihypertensive medication or had a dose increase of an existing medication versus only 2.2% of the Axiron group"

"around 45% of participants receiving Tlando treatment had a reduction in HDL cholesterol levels, falling below normal range by the conclusion of the study. "

do we ignore all these findings? the answer is likely in the middle maybe not as bad as some studies show but also not near zero as the DR 10000% misleadingly says