Anyone tried testosterone base (no ester)?

readalot

Active Member
But is there something special about doing it three times with the nasal gel? Maybe in the the Natesto product development phase they experimented with different frequencies? Are there any references for the half-life of testosterone in oil? What if it is hours instead of minutes? If so then a single morning injection would somewhat approximate a natural rhythm. Natural men do experience "hypogonadal" testosterone levels at their troughs.

From literature I've seen plotting hourly LH and endogenous testosterone levels over the course of a day, there's quite a distribution in terms of what's classified as "normal". If I had to do it over, may start a career studying the frequency response of the HPG axis. Fascinating guys, thank you.
 

madman

Super Moderator
But is there something special about doing it three times with the nasal gel? Maybe in the Natesto product development phase they experimented with different frequencies? Are there any references for the half-life of testosterone in oil? What if it is hours instead of minutes? If so then a single morning injection would somewhat approximate a natural rhythm. Natural men do experience "hypogonadal" testosterone levels at their troughs.


But is there something special about doing it three times with the nasal gel? Maybe in the Natesto product development phase they experimented with different frequencies?

I think with multiple peaks (2-3x daily) it would more effective and you would reap the overall beneficial effects regarding (energy/mood/libido/erectile function/body composition).

They state that testosterone levels or symptoms are used to guide titration decisions between either twice daily or three times a day doses used to restore testosterone levels to the normal range.

If dosing once daily was truly optimal there would be no need for 2-3 times/day application


*Based on the data, Acerus believes that the mechanism of action of NATESTO® is unique whereby the peaks in testosterone generated by NATESTO® dosing provide efficacy and improvement of symptoms, while the time between doses (4-8 hours) allows for the maintenance of testicular testosterone production and sperm production.

*The 24-hour pharmacokinetic profile of testosterone for patients on TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur on average every 2 hours. A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h).

*Natesto, a testosterone-based nasal gel, is self-administered three times per day. Approximately 40 minutes after administration, testosterone levels return to normal, although Natesto’s half-life is widely variable, between 10 and 100 minutes.





Are there any references for the half-life of testosterone in oil? What if it is hours instead of minutes? If so then a single morning injection would somewhat approximate a natural rhythm.

Not that I have come across for an oil-based unesterified T and looking through the studies done using esterified T I find it hard to believe that the carrier oil would have any impact on the delaying the absorption rate to any significant degree.

Let alone the volume of oil-injected using such a low daily dose (100mg/ml strength-based T) would be a measly 10 units/.10 ml

*The pharmacokinetics and pharmacodynamics of androgen esters are therefore primarily determined by ester side-chain length, the volume of oil vehicle, and site of injection via hydrophobic physicochemical partitioning of the androgen ester between the hydrophobic oil vehicle and the aqueous extracellular fluid.

The half-life of unmodified T is 10 min.

Endogenous testosterone secretion is likewise pulsatile and diurnal, with the highest plasma concentrations occurring at about 8 A.M. and the lowest at about 8 P.M.




Natural men do experience "hypogonadal" testosterone levels at their troughs.

Indeed!

Many healthy men, considered to be eugonadal, do have testosterone levels in the hypogonadal range during different times during the day.

The main difference is these men have a healthy functioning hpta let alone are not experiencing any low-t symptoms.
 

Stanfoo

Member
Nothing natural about spiking your T levels once daily only to be back to hypogonadal.

Natural men do experience "hypogonadal" testosterone levels at their troughs.

Indeed!

Many healthy men, considered to be eugonadal, do have testosterone levels in the hypogonadal range during different times during the day.

You made a claim but then later contradicted it. I assume you agree it's natural to have fluctuating highs and lows throughout the day.

The main difference is these men have a healthy functioning hpta let alone are not experiencing any low-t symptoms.

So what exactly is your argument here? From that quote, you're saying having lows in the hypogonadol range is normal only in men with normal hpta functions. So you're implying it's NOT OK for someone on trt (who doesn't have normal hpta functions) to have lows in the hypo range? That doesn't make any sense.

The goal of trt is to achieve optimal well being through exogenous T with a protocol that mimics that of a normal males' natural production of T. What is "nothing natural" about a protocol that'd produce a large high and low? (which we've established does occur in normal men).

You're all over the place.
 

madman

Super Moderator
You made a claim but then later contradicted it. I assume you agree it's natural to have fluctuating highs and lows throughout the day.



So what exactly is your argument here? From that quote, you're saying having lows in the hypogonadol range is normal only in men with normal hpta functions. So you're implying it's NOT OK for someone on trt (who doesn't have normal hpta functions) to have lows in the hypo range? That doesn't make any sense.

The goal of trt is to achieve optimal well being through exogenous T with a protocol that mimics that of a normal males' natural production of T. What is "nothing natural" about a protocol that'd produce a large high and low? (which we've established does occur in normal men).

You're all over the place.


You missed the point I was trying to get across which is a fault on my part for not being specific enough.

When I stated:

You are in no way mimicking the natural 24hr circadian rhythm of a healthy young male where levels peak in the early am and decline in the late afternoon/early evening.

Eugonadal!

Nothing natural about spiking your T levels once daily only to be back to hypogonadal.

be back to hypogonadal (I meant suffer low-t symptoms).



I should have been more specific when I say eugonadal I mean having a healthy functioning hpta as oppose to a hypogonadal male (dysfunctional hpta).

During the natural 24hr circadian rhythm T levels peak in the early am and decline in the late afternoon/early evening.

During the trough low periods, these same healthy young males are not experiencing any low-t symptoms.

In your case, you have a dysfunctional hpta and suffer from low testosterone.

Most men would seek out trt and yes as I have stated numerous times over the years the goal of trt is to replace physiological levels through the use of exogenous T which results in relief/improvement of low-t symptoms and increased overall well-being while at the same time avoiding/minimizing and potential side-effects and keeping blood markers healthy long-term.

The majority of men would be on a protocol that would result in having healthy TT/FT levels throughout the week by keeping T levels stable and avoiding too low of a trough.

As you very well should know maintaining stable levels and minimizing the peak---> to trough can have a big impact on the overall effectiveness.

A large percentage of men are using intramuscular/subcutaneous injections using various injection protocol (once weekly, twice weekly, M/W/F, EOD, daily) and in no way are mimicking the natural 24hr circadian rhythm of a healthy young male.

Steady-state, many are running levels well into the supra-physiological range 24/7 let alone the hpta is shutdown.

The closest you could get to mimicking the natural 24hr circadian rhythm would be using the T patch or transdermal but again your hpta is still shutdown.

Top it off with the fact that when using exogenous T we are forcing levels upon ourselves that the body would never produce naturally.

Natural endogenous testosterone secretion is pulsatile and diurnal.



The point I was trying to make is that there is nothing natural about spiking your T once daily only to end up back to being hypogonadal as in experiencing low-T symptoms as I feel that your protocol using an oil-based unesterified T injected once daily would not be optimal for relieving/improving low-t symptoms and overall well-being.

Doubtful anyone treating low-t symptoms would feel great overall spiking T levels once daily using an oil-based unesterified T which would most likely result in a short-lived peak only to end back to your very low natty T levels.

So how many hours during a 24hr period would your T levels be optimal?

Again on such protocol injecting an oil-based unesterified T your levels will most likely spike quickly and fall off fast.

As I stated earlier it would be a piss poor protocol to treat low-t symptoms let alone long-term.
 

Willyt

Active Member
How much mg testosterone base/day do you think would be safe to not cause suppression? I could be the guinea pig and test your theory out. Was planning on running low dose test base daily anyway once I get it.
@Stanfoo - I was thinking along same line and experimented with Natesto once per day prior to workout. Just posted this thread.

As you can see, the results were encouraging, but Natesto’s nasal administration was not the right vehicle for me. I would much prefer injections. For this limited purpose, TNE sounds interesting. Down the rabbit hole I go.
 

Bigben

New Member
@Stanfoo - I was thinking along same line and experimented with Natesto once per day prior to workout. Just posted this thread.

As you can see, the results were encouraging, but Natesto’s nasal administration was not the right vehicle for me. I would much prefer injections. For this limited purpose, TNE sounds interesting. Down the rabbit hole I go.
Why rabbit hole. Just get that shit in you asap. Then see how you feel in a month.
 

madman

Super Moderator
I've used suspension tons. It's awesome at 20 mg a day. Anything less isn't worth it. Great stuff if you u can find micronized that goes thru a 27g slin. Daily or EOD work good.

Such a dose of unesterified T would be overkill for most as it would easily have FT levels through the roof!

Would be the equivalent of injecting 200 mg TC/week which is a whopping dose for trt especially when split into more frequent injections.

Sure some men may need what would be considered the higher end dose but it is far from common.

Most men can easily achieve a healthy let alone absurdly high trough FT on 100-150 mg T whether split twice weekly (every 3.5 days), M/W/F, EOD let alone daily.

140 mg unesterified T (suspension) = 140 mg active T

200 mg esterified T (cypionate) = 140 mg active T




Rare anyone is using TS for trt.

Not only do you need to inject very frequently but more importantly the majority would be relying on a black market/UGL source.

Unless you have a trusted reliable source there is a good chance that it is underdosed, unsterile, or pure bunk!


*Currently, testosterone suspension is still available in the U.S., but only through private compounding, pharmacies, which may produce the drug on special orders from a licensed doctor.


*
Availability

Pharmaceutical preparations containing testosterone in an aqueous suspension remain scarce. The bulk of the supply presently comes from underground and export steroid manufacturers. In reviewing some of the remaining products and changes in the global pharmaceutical market, we have made the following observations. Testosterone suspension has been unavailable in the United States for many years now. No old products should still be in circulation. Because the FDA never officially withdrew this drug, it can be specially ordered through a small number of compounding pharmacies. Anything else bearing a U.S. manufacturer name is counterfeit. Testosterone suspension is still produced in India under the Aquaviron brand name, now by Piramal HC. It comes in the strength of 25 mg/mL, and is packaged in 1 mL ampules.
 

Willyt

Active Member
*Currently, testosterone suspension is still available in the U.S., but only through private compounding, pharmacies, which may produce the drug on special orders from a licensed doctor.
The underground aspect would scare me away. I wonder if Defy/Empower would prescribe it?

I am still curious as to whether such a fast acting T could be used to trigger "on-demand" libido similar to how one uses Viagra for ED. The idea would be that you would stay within physiological range while on TRT and then supplement with TNE sparingly since you would not want the side effects of those higher levels on a daily basis.

That of course assumes that a supraphysiological level of free T guarantees increased libido, which seems to have been refuted many times on this forum.
 
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madman

Super Moderator
Will oral micronized Testosterone base work for TRT? If yes, what dose?

Unmodified T.....no!

Your only options would be Jatenzo® (testosterone undecanoate capsules) recently approved in the US, or ANDRIOL® (testosterone undecanoate capsules) which is only available in Canada.

17a-methyltestosterone is no longer prescribed/used due to hepatoxicity.

*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.



*PHARMACOLOGY OF ORAL TESTOSTERONE THERAPY

Oral administration of exogenous TT historically has proven to be unsuccessful. Despite adequate absorption in the gastrointestinal system, this form of testosterone undergoes extensive first-pass metabolism through the liver, and thus requires ingestion of supraphysiological doses to attain therapeutic serum levels [14]. As a way to circumvent the liver metabolism pathway, research efforts to administer oral testosterone have taken two primary paths: alkylation of testosterone at the carbon-17 position and fatty-acid esterification of testosterone to create a testosterone ester (Fig. 1).

Alkylation of testosterone at carbon 17α results in 17αmethyltestosterone which allows for the ability to bypass the first metabolism in the liver. However, this modification has been linked to significant liver toxicity including cholestasis, hepatitis, and hepatic adenocarcinoma [15–17] and lowering of HDL cholesterol [18, 19].
The effects of methyltestosterone on liver function were first described in the 1940s, with studies of liver function demonstrating elevations in both serum direct and indirect bilirubin levels [19]. Foss and Simpson also described a case series of 42 patients who developed jaundice during methyltestosterone therapy [20]. They noted that the duration of therapy to the onset of jaundice ranged from 8 days to 10 months and withdrawal of methyltestosterone therapy resulted in remission of hepatocellular dysfunction within a few days to weeks. Recent work has focused on testing the effects of synthetic androgens on liver function utilizing animal models [21] and has corroborated prior work demonstrating direct increases in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and sorbitol dehydrogenase. Therefore, methyltestosterone is largely not recommended for the management of male hypogonadism [6, 22].

Esterification of testosterone at carbon 17β yields testosterone esters
such as testosterone cypionate, testosterone propionate, and testosterone undecanoate (TU). Specifically for TU, this modification allows testosterone to be absorbed via the lymphatic system and therefore bypass liver degradation. An early oral TU formulation (ANDRIOL®) was approved for use in many countries but never in the United States. This formulation is heavily reliant on dietary fat intake as a means of increasing absorption and therefore leads to significant intra- and inter-patient variability in testosterone response [23, 24]. This results in the need to dose hypogonadal men with several capsules three or more times daily affecting compliance. Several studies have also demonstrated both gastrointestinal and liver adverse effects including severe cholestasis and jaundice [25, 26]. Consequently, these oral TU formulations have never been widely utilized to treat TD in the United States although they remain available in many countries.
 

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