High hematocrit prevalence with intranasal vs. intramuscular testosterone

[madman]

Sperm parameters maintained in most men taking nasal testosterone gel

1:08/3:46

 

[M.J]

Thanks very much again @madman. You are a machine.

@Cataceous, I've thought quite a bit about this as once or twice weekly TC really does a number on my Hct.

From the paper above:



Reference 21:

Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets

Objectives Testosterone formulations that have more steady-state pharmacokinetics, such as subcutaneously implanted testosterone pellets, may cause less erythrocytosis than i.m. injections of shorter acting androgen esters. We, therefore, sought to define the prevalence, predictors, and...

eje.bioscientifica.com

Seems to me you'd need something with a very short half life like Natesto or even the creams with crystalline testosterone (half life of hours) to really get the benefit here on reduced Hct.

Let's say you are doing 80 mg per week either 1 weekly injection or breaking it up daily:

View attachment 10306

Either way your trough never drops below physiological. Although AUC invariant, seems like these papers indicate you need time under physiological test levels in order to reap the benefit on your Hct. If I remember correctly trying to trace back the kinetics of testosterone on hepcidin suppression and to EPO, it's first order and you'd reach saturation, so whether you do Test Ester once a day (weekly dosage / 7) or once weekly (weekly dosage / 1) you run into the same problem (trough never drops below physiologic range). To turn off hepcidin suppression and slow down erythropoiesis in an interval fashion, you have to drop test levels intermittently below where they activate the chemical cascade.

Thanks to you guys for bringing this up. Curious your thoughts.

There is seldom a free lunch, bummer.

I saw a Doctor years back he prescribed one injection weekly and put me in daily cream. I used to think he doesn’t know what he is doing, but I recently took an appointment withhim to review my protocol.

currently doing 100mg sustanon, doing good with it but trying to get better and libido anderecrion are not optimum yet.

 

[tareload]

Very nice paper @madman, thank you.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels - PMC

Pharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile ...

www.ncbi.nlm.nih.gov

For someone already shut down after esterified testosterone usage, would be interesting to see if they could restore HPG function (partial or complete LH recovery) while also providing symptom relief during the potential recovery period. This approach may be much more effective that the typical "PCT" methods used with a SERM? An eager expermentalist might vary the daily applications to spend more time below physiological to see if that provided more "driving force" for pituitary.

View attachment 10387

View attachment 10388

Also, I did pick up on this part of the discussion:

Thus, TNG’s ultradian profile is the means to maintain an active HPG. Despite modest Cavg, significant Cmax values may be sufficient for positive symptom outcomes. TNG has up to 12 hours of trough time at or below patients’ baseline (i.e., below the normal range), which is likely a factor in limiting unwanted anabolic effects on hematocrit [22].

Interesting proposition is whether you could use this tool to recover an active HPG as opposed to maintain using frequency modulation. Opens up a lot of potential options but I am probably down a rabbit hole here.

I appreciate it.

Going to try and recover (rather than maintain) my HPG via a troche rather than testosterone nasal gel. I'll report back my results.

Interesting reading:

https://www.tandfonline.com/doi/abs/10.1080/cmt.6.2.104.111

If one is methodical with the troche, my bet is you can also simulate multiple pulses per day (I'll probably just see if I can live with one in the AM to start) with the troche.

For someone who may be secondary (HH), this could be an interesting approach to potential maintain the LF/FSH you have and then supplement with some exogenous T. I aim to find out and potentially maintain upstream pathways. I've corrected the Hct issue by dropping to 60 mg/wk of Test Cyp (once weekly sub-q) but this could be an interesting alternative. With appropriate protocol, the theory and data below show some promise.

Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women

With this type of pulse (and starting at one a day), test and see if you recover LH/FSH. Then ramp up to two or more and repeat until LH inhibition appears. I can say that going cold turkey for a month was no fun (Total T came back at 87 ng/dL). After that experience I now know what true testosterone deficiency is.

Thanks very much to a very intelligent and kind physician for working with me on this. Would make for a very good paper even if anecdotal and give partial HH guys another option to do TRT while also potentially preserving whatever LH/FSH they have. I don't claim to understand the total long-term value of preserving whatever LH/FSH function you have (diurnal pulsing) vs shutdown with test ester.

Thanks for starting this thread @madman and for your discussion @Cataceous

 

[tareload]

Note very different time profile in Fig. 2 above (troche) vs Striant below:

STRIANT® Package Insert & Patient Package Insert

Pharmacokinetics
Absorption

When applied to the buccal mucosa, Striant® slowly releases testosterone, allowing for absorption of testosterone through gum and cheek surfaces that are in contact with the buccal system. Since venous drainage from the mouth is to the superior vena cava, trans-buccal delivery of testosterone circumvents first-pass (hepatic) metabolism. Following the initial application of Striant®, the serum testosterone concentration rises to a maximum within 10-12 hours. The mean maximum (Cmax) and mean average serum total testosterone concentrations for the 12 hour dosing period (Cavg(0-12)) are within the normal physiologic range.

 

[tareload]

More early data from Striant SR study:

Note again very different pharmacokinetics than you'd expect with a fast dissolving troche. See discussion I included below. If I am shooting for recovery of HPTA, I am taking the fast dissolving troche over the sustained release.


Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men

 

[Fortunate]

Very nice paper @madman, thank you.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels - PMC

Pharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile ...

www.ncbi.nlm.nih.gov

For someone already shut down after esterified testosterone usage, would be interesting to see if they could restore HPG function (partial or complete LH recovery) while also providing symptom relief during the potential recovery period. This approach may be much more effective that the typical "PCT" methods used with a SERM? An eager expermentalist might vary the daily applications to spend more time below physiological to see if that provided more "driving force" for pituitary.

View attachment 10387

View attachment 10388

Also, I did pick up on this part of the discussion:

Thus, TNG’s ultradian profile is the means to maintain an active HPG. Despite modest Cavg, significant Cmax values may be sufficient for positive symptom outcomes. TNG has up to 12 hours of trough time at or below patients’ baseline (i.e., below the normal range), which is likely a factor in limiting unwanted anabolic effects on hematocrit [22].

Interesting proposition is whether you could use this tool to recover an active HPG as opposed to maintain using frequency modulation. Opens up a lot of potential options but I am probably down a rabbit hole here.

I appreciate it.

@readalot, I have wondered the same (can you use Natesto to wean off TRT without going through a formal restart protocol?)

Have you successfully stopped TRT? How did you do it? Do you have any additional thoughts on Natesto?

I haven't been able to tolerate creams and injections long term, but if on them long enough, I see certain benefits I don't see as much with Natesto. While I tolerate and even appreciate the benefits of Natesto, I also wonder if the effort is worthwhile? Stated another way: Do I get actual benefit from Natesto that I wouldn't feel if successfully weaned off TRT?

Currently, my options are: (1) Status quo = Natesto and daily hCG, (2) Try Empower's nasal option, hoping there may be some benefit over Natesto, or (3) Try a restart protocol to see how I feel compared to being on Natesto.

In any case, would love to hear if you or anyone else has leveraged Natesto to wean off TRT?

 

[madman]

@readalot, I have wondered the same (can you use Natesto to wean off TRT without going through a formal restart protocol?)

Have you successfully stopped TRT? How did you do it? Do you have any additional thoughts on Natesto?

I haven't been able to tolerate creams and injections long term, but if on them long enough, I see certain benefits I don't see as much with Natesto. While I tolerate and even appreciate the benefits of Natesto, I also wonder if the effort is worthwhile? Stated another way: Do I get actual benefit from Natesto that I wouldn't feel if successfully weaned off TRT?

Currently, my options are: (1) Status quo = Natesto and daily hCG, (2) Try Empower's nasal option, hoping there may be some benefit over Natesto, or (3) Try a restart protocol to see how I feel compared to being on Natesto.

In any case, would love to hear if you or anyone else has leveraged Natesto to wean off TRT?

Will have a better idea soon enough!

The Effects of Natesto For Treatment Of Hypogonadism

https://clinicaltrials.gov/ct2/show/NCT04717362 Sponsor: Baylor College of Medicine Information provided by (Responsible Party): Larry I. Lipshultz, Baylor College of Medicine Detailed Description: Testosterone replacement therapy (TTh) is becoming increasingly common among men of...

www.excelmale.com

 

[Fortunate]

Will have a better idea soon enough!

The Effects of Natesto For Treatment Of Hypogonadism

https://clinicaltrials.gov/ct2/show/NCT04717362 Sponsor: Baylor College of Medicine Information provided by (Responsible Party): Larry I. Lipshultz, Baylor College of Medicine Detailed Description: Testosterone replacement therapy (TTh) is becoming increasingly common among men of...

www.excelmale.com

It’s an interesting city, but not totally clear what they are trying to answer. Are they trying to use a Natesto as a bridge to total cessation of TRT or as an alternative to whatever TRT they were on before? Also relevant is if you use a Natesto as a bridge, how do you get off of that eventually?

 

[madman]

It’s an interesting city, but not totally clear what they are trying to answer. Are they trying to use a Natesto as a bridge to total cessation of TRT or as an alternative to whatever TRT they were on before? Also relevant is if you use a Natesto as a bridge, how do you get off of that eventually?

It is being used as a Standard Reboot Protocol (26 weeks) for patients coming off TTh.


Primary Outcome Measures :

1. Change in Semen Analysis [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   Change in Total Motile Sperm

Secondary Outcome Measures :

1. Change in Hypogonadal Panel [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   change in blood LH levels
2. Change in Hypogonadal Panel [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   change in blood FSH levels
3. Change Hypogonadal Panel [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   change in blood Testosterone levels
4. Change in Hypogonadal Panel [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   change in blood E2 levels
5. Change in Quality of Life Questionnaire [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   Change in SF36 score
6. Change in Quality of Life Questionnaire [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   Change in IPSS score
7. Change in Quality of Life Questionnaire [ Time Frame: Baseline, 14 weeks, 26 weeks. ]
   Change in IIEF score

The spontaneous recovery of spermatogenesis after cessation of TTh is possible but may take months to years and cause the patient to experience a new onset of severe hypothalamic hypogonadal symptoms. Human chorionic gonadotropin (HCG) is a naturally occurring protein that mimics LH and may be used as a therapy to support the return of spermatogenesis quickly with minimal side effects and resolve hypogonadal symptoms. Studies have shown that testosterone-induced infertile patients can recover sperm in the ejaculate in 4.6 months when treated with HCG supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant FSH. With the cessation of TTh, despite the use of LH stimulatory protocols, these patients still experience hypogonadal symptoms.


In this prospective study, the investigators seek to confirm the role of Natesto to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional TTh.

 

[madman]

@readalot, I have wondered the same (can you use Natesto to wean off TRT without going through a formal restart protocol?)

Have you successfully stopped TRT? How did you do it? Do you have any additional thoughts on Natesto?

I haven't been able to tolerate creams and injections long term, but if on them long enough, I see certain benefits I don't see as much with Natesto. While I tolerate and even appreciate the benefits of Natesto, I also wonder if the effort is worthwhile? Stated another way: Do I get actual benefit from Natesto that I wouldn't feel if successfully weaned off TRT?

Currently, my options are: (1) Status quo = Natesto and daily hCG, (2) Try Empower's nasal option, hoping there may be some benefit over Natesto, or (3) Try a restart protocol to see how I feel compared to being on Natesto.

In any case, would love to hear if you or anyone else has leveraged Natesto to wean off TRT?

Highly doubtful there will be any significant difference in absorption let alone effectiveness between Natesto and Defys compounded Nasal Cream.

Application site reaction.....hard to say.

Keep in mind that the non-medicinal ingredients listed in the compounded version are numerous.


post #13

My pre-workout Natesto experiment - Embrace your natural trough!

What if you could enjoy the benefits of exogenous testosterone - even if on a limited basis - while minimizing many of the usual side effects? I was determined to find out through a very unscientific experiment with Natesto, a short-acting nasal testosterone gel discussed numerous times on...

www.excelmale.com

 

[Fortunate]

Highly doubtful there will be any significant difference in absorption let alone effectiveness between Natesto and Defys compounded Nasal Cream.

Application site reaction.....hard to say.

Keep in mind that the non-medicinal ingredients listed in the compounded version are numerous.


post #13

My pre-workout Natesto experiment - Embrace your natural trough!

What if you could enjoy the benefits of exogenous testosterone - even if on a limited basis - while minimizing many of the usual side effects? I was determined to find out through a very unscientific experiment with Natesto, a short-acting nasal testosterone gel discussed numerous times on...

www.excelmale.com

I tend to agree. I don't know how the ingredient list compares to Natesto, but I am a general believer that Less is More!

 

[madman]

I tend to agree. I don't know how the ingredient list compares to Natesto, but I am a general believer that Less is More!

Testosterone Nasal Gel-cream

Non-medicinal ingredients: 29

What are the ingredients in NATESTO?

Medicinal ingredient: Testosterone.

Non-medicinal ingredients: Castor oil, colloidal silicon dioxide, oleoyl polyoxylglycerides.


* slightly yellow gel


NATESTO

Non-medicinal ingredients: 3

 

[Fortunate]

Testosterone Nasal Gel-cream

Non-medicinal ingredients: 29
View attachment 16306



What are the ingredients in NATESTO?

Medicinal ingredient: Testosterone.

Non-medicinal ingredients: Castor oil, colloidal silicon dioxide, oleoyl polyoxylglycerides.


* slightly yellow gel


NATESTO

Non-medicinal ingredients: 3

Boom! Great information, and I definitely feel lazy not pulling it myself.

Thanks again.

 

[tareload]

Some more intraday profiles:

Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men

AbstractObjective. To investigate the relationship between LH and testosterone (T), which characteristics associate with the strength of this relationship,

academic.oup.com

Age Attenuates Testosterone Secretion Driven by Amplitude-Varying Pulses of Recombinant Human Luteinizing Hormone during Acute Gonadotrope Inhibition in Healthy Men

Abstract. Context: Whether testosterone (Te) depletion in aging men reflects deficits in the testis, hypothalamus, and/or pituitary gland is unknown.Object

academic.oup.com