Androgel Not working

[Rclouviere]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

 

[Vince]

Efficacy of changing testosterone gel preparations (Androgel or Testim) among suboptimally responsive hypogonadal men - PubMed

The study objective was to evaluate the efficacy of changing testosterone gel preparations among suboptimally responsive hypogonadal men. The records of all hypogonadal men on gel (Testim or Androgel) testosterone replacement therapy (TRT) were reviewed to identify men who underwent a brand...

pubmed.ncbi.nlm.nih.gov

 

[Systemlord]

Anyone else have this issue?

I had the same issue, lower levels than pre-TRT. My pre-TRT levels was 91 and 120. Poor response to Androgel is commonplace.

It's long coming and time you move to a different delivery system.

You won't have this problem with injections or oral T, the latter not currently available to you.

 

[Melody68]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

I was on it for almost 4 months, big waste of time. Went to injectible enanthate, never looked back.

 

[Systemlord]

I saw a study from 2007 where participants using androgel weren’t seeing results.

The Traverse trial saw the same thing, men with underwhelming lower end testosterone levels.

 

[ziegen]

The only problem is with the amount of Testosterone you're applying. The skin absorbs only about 8-14% of the Testosterone via dermal applications. Most men who successfully do TRT with topical solutions usually use about 100-400mg of Testosterone per day. Typically 10% or 20% (100mg/ml or 200mg/ml) Testosterone creams are used in successful cases. Meanwhile you have a 1.62% (16.2mg/ml) gel, which makes it hard to apply a proper dose. Additionally the gels are usually alcohol based so you can't apply the where your skin absorbs the most, the scrotum. Ask your doctor to switch you to a properly dosed cream, if that's available and if you wish to continue with dermal applications.

 

[madman]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

Seeing as you have been using the TD gel for 12 months then you were clearly benefiting in some way as it is highly doubtful one would put up with feeling shitty that long!

Have no clue where your TT/FT level sits on such as you never posted labs but if you are dosing the 1.62% (4 pumps daily) and are not hitting a high enough FT then you are a poor responder.

The bioavailability of transdermal T (standard application) is around 9-13%.

*Only approximately 10 % of the testosterone applied on the skin surface is absorbed into the circulatory system during a 24-h period.

Most men using the standard 1% Androgel packets or 1% Testim tubes would need the higher-end daily dose of 100 mg T (10 mg T/day) to achieve stellar/high FT levels and again that is if you have no issues with absorption!

Some men can easily achieve a high-end/high TT and more importantly FT level when using the big pharma TD gels but the higher-end dose would be needed.

Unfortunately many men end up being poor responders due to issues with absorption of the transdermal T (standard body application).

In most cases this can be easily remedied by switching to a higher strength compounded T cream applied scrotally!

If anything you could give Testim a go before throwing in the towel as it has been shown to be more effective than Androgel possibly due to the addition of an emollient which can improve absorption.

Just keep in mind whether using Androgel or Testim the higher end dose would be needed in most cases in order to achieve a high-end/high TT/FT level.

If you do not fare well on such due to issues with absorption than a higher strength compounded T cream applied scrotally would be the most sensible move.

If you are ready to move on then oral TU (Jatenzo, Kyzatrex or Tlando) or injectable TC/TE/TP/T-blend is where it's at!

I would give Kyzatrex a go before jumping on injections as oral TU would be a superior formulation when it comes to minimizing sides especially elevated hematocrit!




*Additionally, some gels include emollients that prevent skin drying and ensure better testosterone absorption. There are data to suggest that this may help achieve better bioavailability and higher serum concentrations [37].

[37] Evaluation of the Pharmacokinetic Profiles of the New Testosterone Topical Gel Formulation, TestimTM, Compared to AndroGel (2003)
T. Marbury, E. Hamill, R. Bachand, T. Sebree and T. Smith








2.2.2) Testosterone Gel

There is a wide range of topical products on the market: Tostrex (Tostran, Fortesta), Androgel (Testogel), Testim and Axiron (solution), and Testavan, which is a 2% testosterone gel, currently under registration in Europe and already approved in Australia in May 2017. In Japan too, a new 2% gel is being developed [16]. Androgel 1% (5 g for 50 mg of T) was the pioneer in topical gel applications. In the EU, it was marketed as Androgel 1.62 (2.5 g for 40.5 mg of T). Then came Testim (Testosterone 1%, 5g for 50 mg of T), followed Tostrex (Tostran), sold as a 2% gel with a starting dose of 3 g (60 mg of testosterone. Fortesta (40 mg of T applied to inner thighs) and Axiron (3ml for 30 mg of T applied to each underarm) are also both 2% testosterone solutions. Testavan, also a 2% testosterone gel, is made of a hydroalcoholic and highly viscous topical formulation (1.15 g for 23 mg of T up to 3.45 g for 69 mg of T). A metered dose dispenser including a hands-free cap applicator allows for minimizing exposure to the hands and potential contamination of other people.




Otherwise you would need to look into a compounded higher strength cream which can be applied standard body application or scrotally which would be superior when it comes to absorption of the T.

Look over the paper (pdf) in this post which is the most up to date paper on Transdermal androgens!

New TRT user and frustrated on 1.62 Gel

I’m 47 and low T, low energy and no gym gains. I’ve had issue with ED and my libido at the moment is nonexistent right now. 2 months ago my TEST was 160 and my free T was 11 pg/ml! My PA started me on 1 pump per day alternating shoulders and then bumped me to 2 pumps per day (one pump each...

www.excelmale.com

Got Test results after 3 months 1% T-Gel . . . very rattled!

I'm 68 and was diagnosed in December with lower T at 314, hematocrit at 47. I decided together with the Endocrinologist to go with his suggestion of 5gms 1% T Gel, the regular starting dose. Fast forward to my first blood test taken yesterday after applying the gel regularly for 3 months. And...

www.excelmale.com

*Some manufacturers provide both options (Table 11.2). Most testosterone gel preparations are formulated as hydroalcoholic gel, others use other enhancers in lotions. When applied to the skin, testosterone is absorbed into the stratum corneum over time, which serves as a reservoir. Testosterone is slowly released into the circulatory system over several hours resulting in steady-state serum levels of the hormone [22]. The release of testosterone from the reservoir continues for about 24 h. Only approximately 10 % of the testosterone applied on the skin surface is absorbed into the circulatory system during a 24-h period.


*Long-term studies with testosterone gel have shown that steady and relatively consistent serum levels of testosterone levels are attained [7],


*Several formulations of testosterone gels are available on the market [1, 2, 27]. Currently available gels vary in testosterone concentration and are usually applied once a day. Their pharmacokinetic profiles are also similar: Androgel 1 %®/ Testogel 1 %® [7], Testim® 1 % [28], Axiron®2 % [29] Fortesta Gel® 2 %/Tostran® 2 % [30], and Androgel 1.62 %® [31]. These transdermal preparations have been proven to be efficient in normalizing serum levels, as well as the reversal of androgen deficiency symptoms for long periods of treatment [24], and have been considered an acceptable form of testosterone substitution by users [5]. The maximum concentration of testosterone achieved is variable depending on the preparation but usually within 2–5 h of application and is maintained for 24 h. When applied in the morning, a profile somewhat similar to the circadian rhythm in healthy men is maintained. Recent studies in older hypogonadal men have shown that after testosterone gel application there were large fluctuations in serum testosterone concentration both within and between patients [8]. Skin structural differences may be one of the causes of these significant variations in the bioavailability of the drug, which poses challenges in predicting the effectiveness of medication and determining an adequate dose, as well as an appropriate time for testing serum testosterone levels [8, 32]. Nontime-dependent pulses of serum testosterone also occur in relation to exercise and skin temperature. Both factors may be mediated through changes in dermal blood flow. Another important issue is the possibility of blood sample contamination when it is drawn at the gel application site, which has led to a spurious increase in measured testosterone levels [33]. A sampling of blood after testosterone gel applications should be done away from the application sites.


*Additionally, some gels include emollients that prevent skin drying and ensure better testosterone absorption. There are data to suggest that this may help achieve better bioavailability and higher serum concentrations [37]. Differences in gel formulations and their pharmacokinetic profiles are a reason why gels cannot be used and dosed interchangeably. Therefore, it is recommended to follow specific instructions on sites for application and dosing of the drug provided in the labeling. Dosing information and recommendations for some of the preparations are presented in Table 11.2. It should be noted that some gels are marketed in various countries under different names but are in fact produced by the same manufacturer.


*At day 90, peak T levels were reached after 4 and 8 hours with 5 g and 10 g T gel application, respectively.

 

[madman]

Efficacy of changing testosterone gel preparations (Androgel or Testim) among suboptimally responsive hypogonadal men - PubMed

The study objective was to evaluate the efficacy of changing testosterone gel preparations among suboptimally responsive hypogonadal men. The records of all hypogonadal men on gel (Testim or Androgel) testosterone replacement therapy (TRT) were reviewed to identify men who underwent a brand...

pubmed.ncbi.nlm.nih.gov

Grober and Lipshultz!

 

[madman]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

If you plan on ditching the TD gels and have no interest in using a higher strength compounded T cream applied scrotally then oral TU would be your best bet before jumping straight to injectable T!

Many benefits here that most men overlook especially when it comes to minimizing sides!

Understanding Testosterone and Muscle Preservation

Never heard about oral TU LOL! In this episode of The Dr. Gabrielle Lyon Show, Dr. Lyon sits down with Shalin Shah, CEO of Marius Pharmaceuticals, to explore the science, benefits, and future of testosterone therapy. Shalin has been a driving force behind bringing Kyzatrex, an FDA-approved...

www.excelmale.com

 

[Rclouviere]

I had the same issue, lower levels than pre-TRT. My pre-TRT levels was 91 and 120. Poor response to Androgel is commonplace.

It's long coming and time you move to a different delivery system.

You won't have this problem with injections or oral T, the latter not currently available to you.

What did you try and what were the results?

 

[madman]

The Traverse trial saw the same thing, men with underwhelming lower end testosterone levels.

Do you even understand why?

Pick out those take-home points here surely you can figure this one out!

LOL!

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Trial Intervention​

Patients were randomly assigned in a 1:1 ratio to receive daily transdermal 1.62% testosterone gel or matching placebo gel provided in metered-dose pumps. Randomization was stratified according to the presence or absence of preexisting cardiovascular disease. To avoid unblinding, the patients and trial team remained unaware of the post-baseline testosterone levels measured at the central laboratory. Dose adjustments to maintain testosterone levels between 350 and 750 ng per deciliter (12.1 to 26.0 nmol per liter) or to respond to a hematocrit greater than 54% were managed centrally by an automated algorithm (additional details are provided in the Supplementary Appendix). Patients who were randomly assigned to placebo underwent sham adjustments to maintain blinding.

Testosterone or placebo was discontinued in patients with testosterone levels that exceeded 750 ng per deciliter or with a hematocrit that exceeded 54% even after adjustment to the lowest dose, as well as in patients who had a new diagnosis of prostate cancer or were deemed to be at risk for suicide; otherwise, the assigned intervention was to be continued for the duration of the trial. The investigators received specific guidelines regarding care or referral to a urologist for patients with an elevated PSA level.

Trial End Points​

The mean (±SD) daily dose of testosterone was 65±22 mg. Serum testosterone levels that were measured approximately 24 hours after the patient had received a dose of testosterone or placebo over the course of the trial are shown in Figure 1 and Table S3. At 12 months, the median increase from baseline in serum testosterone levels was 148 ng per deciliter; interquartile range, 34 to 312 (5.1 nmol per liter; interquartile range, 1.2 to 10.8) in the testosterone group, as compared with a median increase of 14 ng per deciliter; interquartile range, −21 to 56 (0.5 nmol per liter; interquartile range, −0.7 to 1.9) in the placebo group. Estradiol levels are summarized in Table S4.




Median Serum Testosterone Levels and Changes in Serum Testosterone Levels over Time.

Shown are median serum testosterone levels (Panel A) and changes from baseline in serum testosterone levels over time since randomization (Panel B). Blood samples were collected 24 hours (±2 hours) after the patient received a dose of testosterone or placebo, preferably in the morning. Vertical bars represent interquartile ranges. To convert serum total testosterone levels to nanomoles per liter, divide by 28.84.

Supplementary Appendix

Titration of Testosterone Dose

The patients randomized to testosterone were started on 40.5 mg of study drug (2 actuations of the pump, each actuation delivering 20.25 mg testosterone) once daily; patients randomized to placebo group were started on 2 actuations of the pump delivering placebo on Study Day 1.The dose of the study drug was titrated based on the measurement of serum testosterone levels at the central laboratory (Labcorp) to achieve and maintain levels between 350 ng/dL and 750 ng/dL, as summarized in table below. The titration of testosterone dose occurred inpatients receiving the active testosterone gel, while concurrent sham dose titrations occurred in patients receiving the placebo gel via the central Interactive Response Technology (IRT)system managed by the designated centrally located staff.

During study weeks 2, 4, 12, and 26 and months 12, 18, 24, 36 and 48, the study patients were asked to come to the clinical trial site for collection of a blood sample for serum testosterone measurement 24 hours (± 2 hours) after the last applied dose preferably in the morning. The titration of the study drug dose was guided by the on-treatment serum testosterone and hematocrit levels, according to the titration plan described below and the titration schedule shown in the table.

Titration instructions were communicated to the sites via the IRT system, while maintaining blinding of the trial site staff with respect to the intervention and the serum testosterone values. The patients randomized to the placebo arm of the trial also underwent sham dose titrations irrespective of their testosterone levels to maintain blinding.

If serum total testosterone concentration was greater than 750 ng/dL, the patient had his dose reduced by one study drug actuation (20.25 mg daily). The patient was then asked to return to the site for a repeat serum total testosterone measurement approximately 2 – 4 weeks after the dose reduction. If the repeat serum total testosterone level was still greater than 750 ng/dL, the patient had his dose reduced by one study drug actuation followed by a repeat serum testosterone assessment approximately 2 weeks after the dose reduction. If serum testosterone level exceeded 750 ng/dL on the lowest dose (20.25 mg daily), the study medication was discontinued, and the patient was continued in the study in accordance with the intent-to-treat study design.

Hematocrit levels were also used to guide dose-titration as follows. Complete blood counts,including hematocrit levels, were obtained during months 6, 12, 18, 24, 36 and 48. If the hematocrit level was > 54%, the patient was asked to come back to the site for another blood draw approximately 2 weeks later to confirm result via the IRT system. Patients with confirmed hematocrit level > 54% were asked about secondary causes of elevated hematocrit (e.g., sleep apnea, severe dehydration) and had their dose reduced by two study drug actuations (40.45 mg daily). If the patient's dose could not be decreased by two actuations (e.g., in patients on 20.25 or 40.45 mg daily dose), then the dose was reduced by one actuation. The patient had a repeat hematocrit assessment approximately 30 to 45 days following the titration. If the repeat hematocrit level was > 54% even after dose titration to the lowest possible dose (20.25 mg daily), the study medication was stopped, and the patient was followed intent-to-treat.




Table S3 – Serum Testosterone Levels (ng/dL) at Scheduled Visits – Overall (top) and OnTreatment (bottom) Values (Safety Set*)

Blood samples were collected 24 hours (± 2 hours) after the last applied dose, preferably in the morning.

*The Safety Set is comprised of all randomized patients who received at least one dose of study drug (testosterone or placebo).

ƚ Excludes testosterone values after study drug discontinuation.

To convert serum total testosterone concentrations to SI units (nmol/L), divide testosterone concentration in ng/dL by 28.84.

 

[Rclouviere]

Seeing as you have been using the TD gel for 12 months then you were clearly benefiting in some way as it is highly doubtful one would put up with feeling shitty that long!

Have no clue where your TT/FT level sits on such as you never posted labs but if you are dosing the 1.62% (4 pumps daily) and are not hitting a high enough FT then you are a poor responder.

The bioavailability of transdermal T (standard application) is around 9-13%.

*Only approximately 10 % of the testosterone applied on the skin surface is absorbed into the circulatory system during a 24-h period.

Most men using the standard 1% Androgel packets or 1% Testim tubes would need the higher-end daily dose of 100 mg T (10 mg T/day) to achieve stellar/high FT levels and again that is if you have no issues with absorption!

Some men can easily achieve a high-end/high TT and more importantly FT level when using the big pharma TD gels but the higher-end dose would be needed.

Unfortunately many men end up being poor responders due to issues with absorption of the transdermal T (standard body application).

In most cases this can be easily remedied by switching to a higher strength compounded T cream applied scrotally!

If anything you could give Testim a go before throwing in the towel as it has been shown to be more effective than Androgel possibly due to the addition of an emollient which can improve absorption.

Just keep in mind whether using Androgel or Testim the higher end dose would be needed in most cases in order to achieve a high-end/high TT/FT level.

If you do not fare well on such due to issues with absorption than a higher strength compounded T cream applied scrotally would be the most sensible move.

If you are ready to move on then oral TU (Jatenzo, Kyzatrex or Tlando) or injectable TC/TE/TP/T-blend is where it's at!

I would give Kyzatrex a go before jumping on injections as oral Tu would be a superior formulation when it comes to minimizing sides especially elevated hematocrit!




*Additionally, some gels include emollients that prevent skin drying and ensure better testosterone absorption. There are data to suggest that this may help achieve better bioavailability and higher serum concentrations [37].

[37] Evaluation of the Pharmacokinetic Profiles of the New Testosterone Topical Gel Formulation, TestimTM, Compared to AndroGel (2003)
T. Marbury, E. Hamill, R. Bachand, T. Sebree and T. Smith








2.2.2) Testosterone Gel

There is a wide range of topical products on the market: Tostrex (Tostran, Fortesta), Androgel (Testogel), Testim and Axiron (solution), and Testavan, which is a 2% testosterone gel, currently under registration in Europe and already approved in Australia in May 2017. In Japan too, a new 2% gel is being developed [16]. Androgel 1% (5 g for 50 mg of T) was the pioneer in topical gel applications. In the EU, it was marketed as Androgel 1.62 (2.5 g for 40.5 mg of T). Then came Testim (Testosterone 1%, 5g for 50 mg of T), followed Tostrex (Tostran), sold as a 2% gel with a starting dose of 3 g (60 mg of testosterone. Fortesta (40 mg of T applied to inner thighs) and Axiron (3ml for 30 mg of T applied to each underarm) are also both 2% testosterone solutions. Testavan, also a 2% testosterone gel, is made of a hydroalcoholic and highly viscous topical formulation (1.15 g for 23 mg of T up to 3.45 g for 69 mg of T). A metered dose dispenser including a hands-free cap applicator allows for minimizing exposure to the hands and potential contamination of other people.




Otherwise you would need to look into a compounded higher strength cream which can be applied standard body application or scrotally which would be superior when it comes to absorption of the T.

Look over the paper (pdf) in this post which is the most up to date paper on Transdermal androgens!

New TRT user and frustrated on 1.62 Gel

I’m 47 and low T, low energy and no gym gains. I’ve had issue with ED and my libido at the moment is nonexistent right now. 2 months ago my TEST was 160 and my free T was 11 pg/ml! My PA started me on 1 pump per day alternating shoulders and then bumped me to 2 pumps per day (one pump each...

www.excelmale.com

Got Test results after 3 months 1% T-Gel . . . very rattled!

I'm 68 and was diagnosed in December with lower T at 314, hematocrit at 47. I decided together with the Endocrinologist to go with his suggestion of 5gms 1% T Gel, the regular starting dose. Fast forward to my first blood test taken yesterday after applying the gel regularly for 3 months. And...

www.excelmale.com

*Some manufacturers provide both options (Table 11.2). Most testosterone gel preparations are formulated as hydroalcoholic gel, others use other enhancers in lotions. When applied to the skin, testosterone is absorbed into the stratum corneum over time, which serves as a reservoir. Testosterone is slowly released into the circulatory system over several hours resulting in steady-state serum levels of the hormone [22]. The release of testosterone from the reservoir continues for about 24 h. Only approximately 10 % of the testosterone applied on the skin surface is absorbed into the circulatory system during a 24-h period.


*Long-term studies with testosterone gel have shown that steady and relatively consistent serum levels of testosterone levels are attained [7],


*Several formulations of testosterone gels are available on the market [1, 2, 27]. Currently available gels vary in testosterone concentration and are usually applied once a day. Their pharmacokinetic profiles are also similar: Androgel 1 %®/ Testogel 1 %® [7], Testim® 1 % [28], Axiron®2 % [29] Fortesta Gel® 2 %/Tostran® 2 % [30], and Androgel 1.62 %® [31]. These transdermal preparations have been proven to be efficient in normalizing serum levels, as well as the reversal of androgen deficiency symptoms for long periods of treatment [24], and have been considered an acceptable form of testosterone substitution by users [5]. The maximum concentration of testosterone achieved is variable depending on the preparation but usually within 2–5 h of application and is maintained for 24 h. When applied in the morning, a profile somewhat similar to the circadian rhythm in healthy men is maintained. Recent studies in older hypogonadal men have shown that after testosterone gel application there were large fluctuations in serum testosterone concentration both within and between patients [8]. Skin structural differences may be one of the causes of these significant variations in the bioavailability of the drug, which poses challenges in predicting the effectiveness of medication and determining an adequate dose, as well as an appropriate time for testing serum testosterone levels [8, 32]. Nontime-dependent pulses of serum testosterone also occur in relation to exercise and skin temperature. Both factors may be mediated through changes in dermal blood flow. Another important issue is the possibility of blood sample contamination when it is drawn at the gel application site, which has led to a spurious increase in measured testosterone levels [33]. A sampling of blood after testosterone gel applications should be done away from the application sites.


*Additionally, some gels include emollients that prevent skin drying and ensure better testosterone absorption. There are data to suggest that this may help achieve better bioavailability and higher serum concentrations [37]. Differences in gel formulations and their pharmacokinetic profiles are a reason why gels cannot be used and dosed interchangeably. Therefore, it is recommended to follow specific instructions on sites for application and dosing of the drug provided in the labeling. Dosing information and recommendations for some of the preparations are presented in Table 11.2. It should be noted that some gels are marketed in various countries under different names but are in fact produced by the same manufacturer.


*At day 90, peak T levels were reached after 4 and 8 hours with 5 g and 10 g T gel application, respectively.

Thanks for the response. My last test was 231 and my PSA went up to 5.6.

When i had labs shortly after taking the gel, the numbers were up; however, over time, they went down.

 

[Rclouviere]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

Another quick question; if i want to stop androgel, for now, do i have to taper even though its not raising my testosterone?

 

[madman]

Another quick question; if i want to stop androgel, for now, do i have to taper even though its not raising my testosterone?

No.


Thanks for the response. My last test was 231 and my PSA went up to 5.6.

When i had labs shortly after taking the gel, the numbers were up; however, over time, they went down.

Your T level is absurdly low and more importantly your FT would be in the gutter!

 

[Rclouviere]

I’ve been using androgel for almost a year at different pumps. Lately, 4 pumps of 1.62. Testestesterone has not gone up at all.

I saw a study from 2007 where participants using androgel weren’t seeing results. 70+ percent saw an i crease when they switched to Testim.

Anyone else have this issue?

 

[Rclouviere]

I had the same issue, lower levels than pre-TRT. My pre-TRT levels was 91 and 120. Poor response to Androgel is commonplace.

It's long coming and time you move to a different delivery system.

You won't have this problem with injections or oral T, the latter not currently available to you.

I heard oral t affects kidneys? And is very expensive?

 

[Rclouviere]

Do you even understand why?

Pick out those take-home points here surely you can figure this one out!

LOL!

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Trial Intervention​

Patients were randomly assigned in a 1:1 ratio to receive daily transdermal 1.62% testosterone gel or matching placebo gel provided in metered-dose pumps. Randomization was stratified according to the presence or absence of preexisting cardiovascular disease. To avoid unblinding, the patients and trial team remained unaware of the post-baseline testosterone levels measured at the central laboratory. Dose adjustments to maintain testosterone levels between 350 and 750 ng per deciliter (12.1 to 26.0 nmol per liter) or to respond to a hematocrit greater than 54% were managed centrally by an automated algorithm (additional details are provided in the Supplementary Appendix). Patients who were randomly assigned to placebo underwent sham adjustments to maintain blinding.

Testosterone or placebo was discontinued in patients with testosterone levels that exceeded 750 ng per deciliter or with a hematocrit that exceeded 54% even after adjustment to the lowest dose, as well as in patients who had a new diagnosis of prostate cancer or were deemed to be at risk for suicide; otherwise, the assigned intervention was to be continued for the duration of the trial. The investigators received specific guidelines regarding care or referral to a urologist for patients with an elevated PSA level.

Trial End Points​

The mean (±SD) daily dose of testosterone was 65±22 mg. Serum testosterone levels that were measured approximately 24 hours after the patient had received a dose of testosterone or placebo over the course of the trial are shown in Figure 1 and Table S3. At 12 months, the median increase from baseline in serum testosterone levels was 148 ng per deciliter; interquartile range, 34 to 312 (5.1 nmol per liter; interquartile range, 1.2 to 10.8) in the testosterone group, as compared with a median increase of 14 ng per deciliter; interquartile range, −21 to 56 (0.5 nmol per liter; interquartile range, −0.7 to 1.9) in the placebo group. Estradiol levels are summarized in Table S4.




Median Serum Testosterone Levels and Changes in Serum Testosterone Levels over Time.

Shown are median serum testosterone levels (Panel A) and changes from baseline in serum testosterone levels over time since randomization (Panel B). Blood samples were collected 24 hours (±2 hours) after the patient received a dose of testosterone or placebo, preferably in the morning. Vertical bars represent interquartile ranges. To convert serum total testosterone levels to nanomoles per liter, divide by 28.84.

View attachment 48926​

Supplementary Appendix

Titration of Testosterone Dose

The patients randomized to testosterone were started on 40.5 mg of study drug (2 actuations of the pump, each actuation delivering 20.25 mg testosterone) once daily; patients randomized to placebo group were started on 2 actuations of the pump delivering placebo on Study Day 1.The dose of the study drug was titrated based on the measurement of serum testosterone levels at the central laboratory (Labcorp) to achieve and maintain levels between 350 ng/dL and 750 ng/dL, as summarized in table below. The titration of testosterone dose occurred inpatients receiving the active testosterone gel, while concurrent sham dose titrations occurred in patients receiving the placebo gel via the central Interactive Response Technology (IRT)system managed by the designated centrally located staff.

During study weeks 2, 4, 12, and 26 and months 12, 18, 24, 36 and 48, the study patients were asked to come to the clinical trial site for collection of a blood sample for serum testosterone measurement 24 hours (± 2 hours) after the last applied dose preferably in the morning. The titration of the study drug dose was guided by the on-treatment serum testosterone and hematocrit levels, according to the titration plan described below and the titration schedule shown in the table.




View attachment 48927


Titration instructions were communicated to the sites via the IRT system, while maintaining blinding of the trial site staff with respect to the intervention and the serum testosterone values. The patients randomized to the placebo arm of the trial also underwent sham dose titrations irrespective of their testosterone levels to maintain blinding.

If serum total testosterone concentration was greater than 750 ng/dL, the patient had his dose reduced by one study drug actuation (20.25 mg daily). The patient was then asked to return to the site for a repeat serum total testosterone measurement approximately 2 – 4 weeks after the dose reduction. If the repeat serum total testosterone level was still greater than 750 ng/dL, the patient had his dose reduced by one study drug actuation followed by a repeat serum testosterone assessment approximately 2 weeks after the dose reduction. If serum testosterone level exceeded 750 ng/dL on the lowest dose (20.25 mg daily), the study medication was discontinued, and the patient was continued in the study in accordance with the intent-to-treat study design.

Hematocrit levels were also used to guide dose-titration as follows. Complete blood counts,including hematocrit levels, were obtained during months 6, 12, 18, 24, 36 and 48. If the hematocrit level was > 54%, the patient was asked to come back to the site for another blood draw approximately 2 weeks later to confirm result via the IRT system. Patients with confirmed hematocrit level > 54% were asked about secondary causes of elevated hematocrit (e.g., sleep apnea, severe dehydration) and had their dose reduced by two study drug actuations (40.45 mg daily). If the patient's dose could not be decreased by two actuations (e.g., in patients on 20.25 or 40.45 mg daily dose), then the dose was reduced by one actuation. The patient had a repeat hematocrit assessment approximately 30 to 45 days following the titration. If the repeat hematocrit level was > 54% even after dose titration to the lowest possible dose (20.25 mg daily), the study medication was stopped, and the patient was followed intent-to-treat.




Table S3 – Serum Testosterone Levels (ng/dL) at Scheduled Visits – Overall (top) and OnTreatment (bottom) Values (Safety Set*)

View attachment 48932

Blood samples were collected 24 hours (± 2 hours) after the last applied dose, preferably in the morning.

*The Safety Set is comprised of all randomized patients who received at least one dose of study drug (testosterone or placebo).

ƚ Excludes testosterone values after study drug discontinuation.

To convert serum total testosterone concentrations to SI units (nmol/L), divide testosterone concentration in ng/dL by 28.84.

That’s the study i referred to.

 

[Systemlord]

I heard oral t affects kidneys? And is very expensive?

There’s a lot of ignorance, bias and fear mongering out there from ignorant people. You might be talking about the older oral T, and not the newer formulations.

 

[Systemlord]

That’s the study i referred to.

The majority of studies are of poorly done and the people doing the studies have an agenda. As far as oral T being expensive, it depends upon your insurance company. Cash pay is much cheaper when you cut the insurance company, middle man out of the loop.

 

[madman]

That’s the study i referred to.

You would mean the 2007 study Vince uploaded in post #2 and I uploaded the paper (pdf) in post #8!

Not the Traverse Trial study I was replying back to Mr. so sure of himself!