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

[madman]

Great stuff. Is this compounded or commercial product? Where do you get it?

Natesto is patented and manufactured by Acerus Pharmaceuticals here in Ontario, Canada.

It is the only big pharma nasal T gel on the market.

Any other nasal T gels/sprays would be compounded.

 

[Fortunate]

Natesto is patented and manufactured by Acerus Pharmaceuticals here in Ontario, Canada.

It is the only big pharma nasal T gel on the market.

Any other nasal T gels/sprays would be compounded.

Thanks to all who have weighed in, including madman. I am very familiar with Natesto. I have been on and off of it over the course of time. I think it is a good product, but the spray has me interested. Might be a bit easier to deal with.

Does anyone else know a compounding pharmacy that makes this or does anyone else have any experience with a spray?

Thanks again.

 

[madman]

Sorry, Fortunate, I should have mentioned that it is compounded. Right now I am using a concentration of 3mg per spray, (18mg per day), but have used 2mg and 4mg at different times. I am not sure it would be acceptable to share source here in the thread.

Hard to believe you would be hitting a high enough TT level on such a dose.

Have you had a blood test done to confirm what serum T levels you are achieving on such a low dose?

The dose used for Natesto is 22.0 mg (twice daily administration) or more commonly 33.0 mg (thrice daily administration) applied every 6-8 hrs which would allow one to achieve high-end T levels temporarily.

Tmax approx. 40 min

Nasal administration of T (4.5% testosterone nasal gel, Natesto) allows for rapid absorption through the nasal mucosa such that serum T levels reach a peak concentration in ∼40 min.

 

[Tester]

Natesto is patented and manufactured by Acerus Pharmaceuticals here in Ontario, Canada.

It is the only big pharma nasal T gel on the market.

Any other nasal T gels/sprays would be compounded.

Yes, you're right, Madman, it's compounded.

 

[Tester]

Hard to believe you would be hitting a high enough TT level on such a dose.

Have you had a blood test done to confirm what serum T levels you are achieving on such a low dose?

The dose used for Natesto is 22.0 mg (twice daily administration) or more commonly 33.0 mg (thrice daily administration) applied every 6-8 hrs which would allow one to achieve high-end T levels temporarily.

Tmax approx. 40 min

Nasal administration of T (4.5% testosterone nasal gel, Natesto) allows for rapid absorption through the nasal mucosa such that serum T levels reach a peak concentration in ∼40 min.

View attachment 13829

I see your point, madman. I find a definite bump at 18mg per day but I have dosed double that. My experience tells me I feel better in the 18-24mg range. In response to the lower test quantities in the dosage - I suspect that the Natesto gel limits absorbtion area and a certain amount goes unutilized picked up in bodily fluids or the carrier agent dries out during respiration (so a higher concentration is needed. (if you dosed 99mg a day via injection you would be at superhuman levels so some must be wasted). This spray/mist covers a much broader surface of the nasal cavity in a thin layer so the uptake is more efficient, I suspect.

 

[madman]

I see your point, madman. I find a definite bump at 18mg per day but I have dosed double that. My experience tells me I feel better in the 18-24mg range. In response to the lower test quantities in the dosage - I suspect that the Natesto gel limits absorbtion area and a certain amount goes unutilized picked up in bodily fluids or the carrier agent dries out during respiration (so a higher concentration is needed. (if you dosed 99mg a day via injection you would be at superhuman levels so some must be wasted). This spray/mist covers a much broader surface of the nasal cavity in a thin layer so the uptake is more efficient, I suspect.

Doubting the T nasal spray will result in better absorption.

The concentration of 4.5% T in Natesto would allow the application of a smaller amount of gel to the nasal cavity improving the absorption and effectiveness.

Only blood work will tell what Tmax levels are truly achieved using lower doses of T nasal spray.

Post labs?


2.2.4 How were the dose and the dosing regimen of NATESTO for the Phase 3 study and TBM product determined?

Reference is made to the minutes of the End of Phase 2 (EOP2) meeting held between the Division and the Sponsor on March 14, 2011 (dated May 4, 2011, under IND 70512 in DARRTS). A Phase 2 study, Nasobol-01-2009, examined the efficacy and tolerability of the 3.2% TBS-1 nasal gel formulation. In this study, the results for the 11 mg T BID dose did not meet the Agency‘s principle acceptance criterion for standard T therapies (i.e., at least 75% of subjects should achieve an average total T concentration within the normal range of 300-1,050 ng/dL). In addition, a linear increase in T concentrations with escalating doses was not achieved. The sponsor believed that the lack of a linear increase suggested that T absorption was limited by the inability of the nasal cavity to hold the tested volumes of the 3.2% TBS-1 formulation.

The dosing regimen selected for the Phase 3 efficacy and safety study (Study TBS-1-2011-03) was based on results from Studies TBS-1-2010-01 and TBS-1-2011-01. Based on the results of Study Nasabol-01-2009, the Sponsor conducted a Phase 2, dose-finding study, TBS-1-2010-01, evaluating higher concentrations of TBS-1 (i.e., 4.0% and 4.5% T w/w) formulations in reduced volumes. Study TBS-1-2010-01 was an open-label, randomized, balanced, 3-treatments (4.0% TID, 4.5% BID, and 4.5% TID), parallel design, dose-finding, PK study of TBS-1 administered intranasally in 22 hypogonadal males (age of 35-73 years). Subjects were randomized to one of the following 3 treatment groups:

 Treatment A (N=8): TBS-1 syringes pre-filled with 125 μL 4.0% gel to deliver 5.0 mg of T per nostril (intranasal) given TID at 9 pm, 7 am, and 1 pm (total dose: 30 mg/day).

 Treatment B (N=7): TBS-1 syringes pre-filled with 150 μL 4.5% gel to deliver 6.75 mg of T per nostril (intranasal) given BID at 9 pm and 7 am (total dose: 27.0 mg/day).

 Treatment C (N=7): TBS-1 syringes pre-filled with 125 μL 4.5% gel to deliver 5.625 mg of T per nostril (intranasal) given TID at 9 pm, 7 am, and 1 pm (total dose 33.75 mg/day).

TBS-1 was administered for 7 days as per treatment group assignment. On Day 7, subjects for all treatment groups returned to their study centers and underwent a 24-hour PK sample collection after the 9 pm dosing. Total T PK profiles and parameters are presented in Figure 4 and Table 6.

Concentrating TBS-1 from 3.2% to 4.5% T (w/w) allowed for administration of a smaller amount of gel, resulting in improved and consistent absorption of T, and a higher response rate (i.e., achieving serum T average concentration [Cavg] values within the normal range) of subjects using 4.0% T and 4.5% T (w/w) versus 3.2% T (w/w) TBS-1 formulation. Regardless of the concentration of formulation and the dose, approximately 86-88% of the subjects had a total T Cavg within the normal range of 300-1,050 ng/dL. Two (2) out of 7 subjects (i.e., Subject 01-005 Cmax = 1,670 ng/dL; Subject 02-006 Cmax = 1,570 ng/dL) who were in the 13.5 mg BID (4.5% w/w) treatment group had a T Cmax > 1,500 ng/dL. While both the BID and TID doses administered in this study had similar Cavg (approximately 400 ng/mL) within the normal range, the 13.5 mg BID (4.5% T w/w) regimen had a Cmax value above the normal range, while the 11.25 mg TID (4.5% T w/w) regimen did not. All 3 treatments also demonstrated expected increases in mean serum DHT and E2 concentrations following TBS-1 administration (data not shown). The major limitation of this study was that it was a parallel study design instead of being a crossover design (that would allow a direct and accurate comparison between treatment groups). Modeling and simulation of profiles for 200 subjects based on data from the 22 subjects from Study TBS-1- 2010-01 supported a reduction from 11.25 mg to 11 mg T per dose without compromising efficacy. Reference is made to Dr. LaiMing Lee’s Clinical Pharmacology review dated September 21, 2011, under IND 70512 in DARRTS.

Study TBS-1-2011-01 was a Phase 1, randomized, crossover study conducted in 12 healthy men (age of 18-28 years), to compare the BA following a single dose of 11 mg T of TBS-1 from a multiple-dose dispenser (i.e., the proposed commercial method of administration) to that following a single dose of 11 mg T of TBS-1 from a prefilled syringe (i.e., the method of administration used in several studies earlier in the TBS-1 development program). A 12-hour baseline T profile was characterized for each subject to determine their endogenous T concentrations. The TBS-1 treatment was administered at 9 pm. A total of 13 blood samples were collected for each subject over a 12-hour post-dose period. Each treatment period was separated by a washout period of at least 6 days.

As shown in Figure 5, the multiple-dose dispenser had higher AUC(0-12) values compared to those with the prefilled syringe, while also having a higher Cmax. Based on this finding, the sponsor decided to select the multiple-dose dispenser as the proposed commercial method of administration.

Based on the findings from Studies TBS-1-2010-01 and TBS-1-2011-01, an 11.0 mg T dose of TBS-1 administered as a 22.0 mg T daily dose (i.e., BID dosing) or 33.0 mg T daily dose (i.e., TID dosing) using the multiple-dose dispenser was selected for the Phase 3 efficacy and safety study (Study TBS-1-2011-03).

Based on the results of the Phase 3 study, TBS-1-2011-03, the final proposed dosing regimen for NATESTO was determined to be 11 mg T TID (i.e., 33 mg/day).

 

[madman]

*Concentrating TBS-1 from 3.2% to 4.5% T (w/w) allowed for administration of a smaller amount of gel, resulting in improved and consistent absorption of T, and a higher response rate

 

[Tester]

Doubting the T nasal spray will result in better absorption.

The concentration of 4.5% T in Natesto would allow the application of a smaller amount of gel to the nasal cavity improving the absorption and effectiveness.

Only blood work will tell what Tmax levels are truly achieved using lower doses of T nasal spray.

Post labs?


2.2.4 How were the dose and the dosing regimen of NATESTO for the Phase 3 study and TBM product determined?

Reference is made to the minutes of the End of Phase 2 (EOP2) meeting held between the Division and the Sponsor on March 14, 2011 (dated May 4, 2011, under IND 70512 in DARRTS). A Phase 2 study, Nasobol-01-2009, examined the efficacy and tolerability of the 3.2% TBS-1 nasal gel formulation. In this study, the results for the 11 mg T BID dose did not meet the Agency‘s principle acceptance criterion for standard T therapies (i.e., at least 75% of subjects should achieve an average total T concentration within the normal range of 300-1,050 ng/dL). In addition, a linear increase in T concentrations with escalating doses was not achieved. The sponsor believed that the lack of a linear increase suggested that T absorption was limited by the inability of the nasal cavity to hold the tested volumes of the 3.2% TBS-1 formulation.

The dosing regimen selected for the Phase 3 efficacy and safety study (Study TBS-1-2011-03) was based on results from Studies TBS-1-2010-01 and TBS-1-2011-01. Based on the results of Study Nasabol-01-2009, the Sponsor conducted a Phase 2, dose-finding study, TBS-1-2010-01, evaluating higher concentrations of TBS-1 (i.e., 4.0% and 4.5% T w/w) formulations in reduced volumes. Study TBS-1-2010-01 was an open-label, randomized, balanced, 3-treatments (4.0% TID, 4.5% BID, and 4.5% TID), parallel design, dose-finding, PK study of TBS-1 administered intranasally in 22 hypogonadal males (age of 35-73 years). Subjects were randomized to one of the following 3 treatment groups:

 Treatment A (N=8): TBS-1 syringes pre-filled with 125 μL 4.0% gel to deliver 5.0 mg of T per nostril (intranasal) given TID at 9 pm, 7 am, and 1 pm (total dose: 30 mg/day).

 Treatment B (N=7): TBS-1 syringes pre-filled with 150 μL 4.5% gel to deliver 6.75 mg of T per nostril (intranasal) given BID at 9 pm and 7 am (total dose: 27.0 mg/day).

 Treatment C (N=7): TBS-1 syringes pre-filled with 125 μL 4.5% gel to deliver 5.625 mg of T per nostril (intranasal) given TID at 9 pm, 7 am, and 1 pm (total dose 33.75 mg/day).

TBS-1 was administered for 7 days as per treatment group assignment. On Day 7, subjects for all treatment groups returned to their study centers and underwent a 24-hour PK sample collection after the 9 pm dosing. Total T PK profiles and parameters are presented in Figure 4 and Table 6.

View attachment 13831
View attachment 13832

Concentrating TBS-1 from 3.2% to 4.5% T (w/w) allowed for administration of a smaller amount of gel, resulting in improved and consistent absorption of T, and a higher response rate (i.e., achieving serum T average concentration [Cavg] values within the normal range) of subjects using 4.0% T and 4.5% T (w/w) versus 3.2% T (w/w) TBS-1 formulation. Regardless of the concentration of formulation and the dose, approximately 86-88% of the subjects had a total T Cavg within the normal range of 300-1,050 ng/dL. Two (2) out of 7 subjects (i.e., Subject 01-005 Cmax = 1,670 ng/dL; Subject 02-006 Cmax = 1,570 ng/dL) who were in the 13.5 mg BID (4.5% w/w) treatment group had a T Cmax > 1,500 ng/dL. While both the BID and TID doses administered in this study had similar Cavg (approximately 400 ng/mL) within the normal range, the 13.5 mg BID (4.5% T w/w) regimen had a Cmax value above the normal range, while the 11.25 mg TID (4.5% T w/w) regimen did not. All 3 treatments also demonstrated expected increases in mean serum DHT and E2 concentrations following TBS-1 administration (data not shown). The major limitation of this study was that it was a parallel study design instead of being a crossover design (that would allow a direct and accurate comparison between treatment groups). Modeling and simulation of profiles for 200 subjects based on data from the 22 subjects from Study TBS-1- 2010-01 supported a reduction from 11.25 mg to 11 mg T per dose without compromising efficacy. Reference is made to Dr. LaiMing Lee’s Clinical Pharmacology review dated September 21, 2011, under IND 70512 in DARRTS.

Study TBS-1-2011-01 was a Phase 1, randomized, crossover study conducted in 12 healthy men (age of 18-28 years), to compare the BA following a single dose of 11 mg T of TBS-1 from a multiple-dose dispenser (i.e., the proposed commercial method of administration) to that following a single dose of 11 mg T of TBS-1 from a prefilled syringe (i.e., the method of administration used in several studies earlier in the TBS-1 development program). A 12-hour baseline T profile was characterized for each subject to determine their endogenous T concentrations. The TBS-1 treatment was administered at 9 pm. A total of 13 blood samples were collected for each subject over a 12-hour post-dose period. Each treatment period was separated by a washout period of at least 6 days.

View attachment 13833

As shown in Figure 5, the multiple-dose dispenser had higher AUC(0-12) values compared to those with the prefilled syringe, while also having a higher Cmax. Based on this finding, the sponsor decided to select the multiple-dose dispenser as the proposed commercial method of administration.

Based on the findings from Studies TBS-1-2010-01 and TBS-1-2011-01, an 11.0 mg T dose of TBS-1 administered as a 22.0 mg T daily dose (i.e., BID dosing) or 33.0 mg T daily dose (i.e., TID dosing) using the multiple-dose dispenser was selected for the Phase 3 efficacy and safety study (Study TBS-1-2011-03).

Based on the results of the Phase 3 study, TBS-1-2011-03, the final proposed dosing regimen for NATESTO was determined to be 11 mg T TID (i.e., 33 mg/day).

Unfortunately, madman, I can only speak anecdotallyas to how I feel with regard to energy and the pumps and gains I have in the gym. My doc wasn't open to prescribing therapy after my initial testing and certainly wouldn't support my independent use. I have no doubt that Nasotest is a good product but it's not something I have ready access to at this time. On an additional note I haven't experienced what I would perceive as exceptional libido. It's there and fine but not ravenous.

 

[Tester]

So

so the Empower nasal product is a cream not a gel? I wonder how it differs considering that Natesto is patented. I may have to try it.

Interesting post-script to my original post. I ran blood test about two weeks after discontinuing Nastesto. My TT was over 500, which was significantly higher than my pre-TRT baseline of 250-300.

Perhaps the pulsing ramped up your natural production somehow?

 

[Willyt]

Perhaps the pulsing ramped up your natural production somehow?

@Tester - I have wondered the same thing. The 500 TT was a surprise considering my pre-TRT baseline. That said, my FT was still slightly below range, which might explain why I wrote in my notes that I felt decent, but not symptom-free at time of blood test.

I tried similar experiment with scrotal cream using it intermittingly (4 days per week). The test results were the opposite with near complete shutdown of HPTA (TT of 123). This is consistent with several Natesto research papers that @madman has posted comparing Natesto versus T transdermal gel, but I figured scrotal cream might fair better because of its fast-acting profile. I ruled that approach out.

 

[Tester]

@Tester - I have wondered the same thing. The 500 TT was a surprise considering my pre-TRT baseline. That said, my FT was still slightly below range, which might explain why I wrote in my notes that I felt decent, but not symptom-free at time of blood test.

I tried similar experiment with scrotal cream using it intermittingly (4 days per week). The test results were the opposite with near complete shutdown of HPTA (TT of 123). This is consistent with several Natesto research papers that @madman has posted comparing Natesto versus T transdermal gel, but I figured scrotal cream might fair better because of its fast-acting profile. I ruled that approach out.

I think there may be something to this ramping up of one's natural production. I can only speak anecdotally because I am not in a situation where I am able to get corroborating blood tests but when I have cycled off the nasal mist I use, (I do this just for good measure from time to time), I don't feel myself crashing down to where I used to be.

With regard to the scrotal cream - one could wonder if location of application is somehow responsible for the utter shutdown? It's literally permeating the site of production.

 

[Match]

Empower também apenas com receita médica? Pois o Natesto exige receita

 

[Eklutna]

Sim. Com receita. Empower e Natesto.

 

[Fortunate]

@Willyt, @Eklutna (it looks like @fifty is gone?), can you post an update? I think I read elsewhere that @Willyt abandoned the nasal route?

I have been on Natesto on an off for years. For me, it's virtually the only form of TRT that does not give me unpleasant side effects. I have never used the Empower nasal gel and I wonder if it may be worth trying (things I'd be considering: is absorption and therefore benefit better than Natesto? is it less likely to make you feel stuffy? Is it less likely to build up gunk?).

If anyone else here has used the Empower compounded nasal gel/cream, please post feedback. I will likely request an Rx in the near future. If so, I will post feedback for anyone interested.

 

[Fortunate]

I just re-read some of the original thread and see some comments that address my questions above. That said, please feel free to chime in with any more feedback about the Empower cream if you have any.

@fifty, do you really think this is the same as the skin cream? I would think that the skin cream would irritate the nasal cavity, but I don't say that with any expertise.

 

[Willyt]

@Willyt, @Eklutna (it looks like @fifty is gone?), can you post an update? I think I read elsewhere that @Willyt abandoned the nasal route?

I have been on Natesto on an off for years. For me, it's virtually the only form of TRT that does not give me unpleasant side effects. I have never used the Empower nasal gel and I wonder if it may be worth trying (things I'd be considering: is absorption and therefore benefit better than Natesto? is it less likely to make you feel stuffy? Is it less likely to build up gunk?).

Regarding your question, I eventually switched from Natesto to low dose 8mg daily propionate.

Per my review above, I can see the appeal of Natesto with its minimal suppression, but I failed to see much progress in symptom resolution other than a nice workout boost. In fairness, I was only using 1x per day (versus the prescribed 3x) because I found the nasal application somewhat annoying and imprecise.

I am still surprised and disappointed that the T spike from Natesto did not boost libido temporarily. As many forum members have said, libido seems to be driven by more than just T contrary to mainstream thought.

You seemed to experience some lifestyle improvements from Natesto like increased confidence, energy, etc. That might be enough to justify continued use. Who knows, I might come back to it if the low dose Prop does not work out!

One question for you - why would you take HCG with Natesto if Natesto has minimal suppressive effect?

 

[Fortunate]

Regarding your question, I eventually switched from Natesto to low dose 8mg daily propionate.

Per my review above, I can see the appeal of Natesto with its minimal suppression, but I failed to see much progress in symptom resolution other than a nice workout boost. In fairness, I was only using 1x per day (versus the prescribed 3x) because I found the nasal application somewhat annoying and imprecise.

I am still surprised and disappointed that the T spike from Natesto did not boost libido temporarily. As many forum members have said, libido seems to be driven by more than just T contrary to mainstream thought.

You seemed to experience some lifestyle improvements from Natesto like increased confidence, energy, etc. That might be enough to justify continued use. Who knows, I might come back to it if the low dose Prop does not work out!

One question for you - why would you take HCG with Natesto if Natesto has minimal suppressive effect?

That's actually a good question and have wondered the same.

I originally started hCG as monotherapy with a local doc when I started TRT. That did not work well. My levels actually dropped, so I started injections and continued hCG. I then became a patient of Dr. Crisler's. We did both injections and cream, and he kept me on hCG, but we went to a low daily dose. After he passed away, I resumed treating locally. Somewhere along the way (maybe 2017, but would have to look up the date), I started Natesto. At the time, I asked if I needed to continue hCG and was advised to do so.

I have on a few occasions asked the same question to the same provider and keep getting advised to stay on it. I don't really have a strong explanation. On the other hand, I assume that it raises my baseline T levels a bit. I have also gone off it for a few stretches. While it's not a home run conclusion, I think I feel better overall on it.

I would prefer to not be on it, as it is annoying to travel with it, keep my kids and their friends from wondering why a vial is in the fridge, etc.

 

[Willyt]

I think there may be something to this ramping up of one's natural production. I can only speak anecdotally because I am not in a situation where I am able to get corroborating blood tests but when I have cycled off the nasal mist I use, (I do this just for good measure from time to time), I don't feel myself crashing down to where I used to be.

This is getting interesting...

As mentioned above, in early 2021 I ran blood test about two weeks after discontinuing Nastesto (1x daily). My TT was over 500, which was significantly higher than my pre-TRT baseline of 250-300 (I tested in this hypogonadal range for 5 years straight pre-TRT for my annual physical).

Fast forward to the present. I quit my low dose daily Propionate of 7-8mg (including experiment with twice daily Prop). I went cold turkey then started using nasal T gel again, this time with Empower's nasal gel pen 2x daily (8am & 4pm).

Went for my annual physical and tested 557 TT (300-890 range) at trough before morning application, nearly double my pre-TRT levels. In addition, my HPTA appears intact with FSH of 3.2 (1.6 - 9.7) and LH of 4.5 (1.5 - 9.3). The boys are back

This notion of quick-acting nasal T gel ramping up natural production is consistent with some of the studies that @madman has cited.

Perhaps a new term is needed: TST (Testosterone Supplementation Therapy)!

It is still early days, but exciting nonetheless. More to come next month when I get full blood panel. I will try to test both trough (before morning application) and peak (1 hour after morning application) and will also provide details on my subjective observations.

 

[TLawyer]

This is getting interesting...

As mentioned above, in early 2021 I ran blood test about two weeks after discontinuing Nastesto (1x daily). My TT was over 500, which was significantly higher than my pre-TRT baseline of 250-300 (I tested in this hypogonadal range for 5 years straight pre-TRT for my annual physical).

Fast forward to the present. I quit my low dose daily Propionate of 7-8mg (including experiment with twice daily Prop). I went cold turkey then started using nasal T gel again, this time with Empower's nasal gel pen 2x daily (8am & 4pm).

Went for my annual physical and tested 557 TT (300-890 range) at trough before morning application, nearly double my pre-TRT levels. In addition, my HPTA appears intact with FSH of 3.2 (1.6 - 9.7) and LH of 4.5 (1.5 - 9.3). The boys are back

This notion of quick-acting nasal T gel ramping up natural production is consistent with some of the studies that @madman has cited.

Perhaps a new term is needed: TST (Testosterone Supplementation Therapy)!

It is still early days, but exciting nonetheless. More to come next month when I get full blood panel. I will try to test both trough (before morning application) and peak (1 hour after morning application) and will also provide details on my subjective observations.

How do you feel? Libido improved?

 

[Willyt]

How do you feel? Libido improved?

I want to wait another couple of weeks before making any conclusions, but initial signs are promising.