Systemlord
Member
No.
Alternating Dosage Every other day on Daily Dosing
- Thread starter Gnairb5
- Start date
Current protocol is 200mg test, 100-125mg nandrolone, 1.35iu’s HGH/ day, 1000iu’s HCG/ week, and 1mg of injectable progesterone/ day. I also inject my test and nandrolone EOD
Systemlord
Member
Systemlord
Member
Thanks.
The graph you've posted is a perfect proof that taking it 3 times a day is the best.You are not understanding the PK.
It is dosed twice daily.
Even then there is no issue with liver toxicity.
Jatenzo, an Oral Testosterone Replacement Therapy
Clarus Therapeutics Announces Commercial Launch and Availability of JATENZO® (testosterone undecanoate) capsules, CIII for the Treatment of Hypogonadism Clarus Therapeutics Announces Commercial Launch and Availability of JATENZO® (testosterone undecanoate) capsules, CIII for the Treatment of...www.excelmale.com
Figure 2: Mean (±SEM) Concentration-Time Profile for NaF-EDTA Plasma Total Testosterone in JATENZO Treated Subjects at Final PK Visit
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JATENZO®: Challenges in the development of oral testosterone
Testosterone therapy (TT) for the treatment of testosterone deficiency (TD) can be administered via several routes of administration. Due to a variety of concerns such as hepatotoxicity, an oral formulation has long been absent in the United States. Recently, JATENZO® (testosterone undecanoate)...
*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
Wake up at 9AM, take one. 6 hours later take another that's 3 PM (40% drop in 6 hours is alot and people still have 6+ hours to go before sleep. Then another one at 9PM.
Some guys like to workout later and they'd totally feel a 40-50% drop in Testosterone levels. I noticed that with the cream.
These studies are done a certain way to impress the FDA, not the most optimal. They want to keep testosterone levels low to mid range
LOL
Have you noticed benefits taking injectable progesterone? Can you take 2mg EOD?
Thats a good question, not sure what the half life of the injectable prog I use is. Maybe @Cataceous would have more insight into this
As far as the benefits, it seems to have helped with acne, and also has made me feel more calm and comfortably socially. Just think I feel more calm, cool and relaxed in general. But not lackadaisical or anything. Might of helped a bit with sleep, but I already slept pretty good, so hard to tell.
How long did it take to feel the positive effects from daily injections?
My shbg came back at 20. So i just started doing daily injections this week
madman
Super Moderator
Really?
If anything most men on trt would want to avoid a surge in T before going to bed.
Testosterone has a tonic effect on the CNS and can easily make one feel amped up let alone have a negative impact on sleep (quality/quantity).
Taking the 3rd dose at 9 pm would have one hitting peak T levels 4 hrs later!
Even then highly doubtful the trough time between doses is going to have a significant impact on the overall effectiveness of oral TU as it is meant to be dosed twice daily.
Natesto is dosed 2-3 times daily and there is a short-lived peak in T 40-60 min post-application with significant trough times between doses yet can be an effective form of T therapy.
If you are truly concerned with achieving let alone maintaining high/very high T levels then you would be wasting your time using Jatenzo let alone Natesto.
Comparison of Testosterone Blood Concentrations from Different TRT Products Versus Normal Diurnal Variations
Abstract Background: To improve symptoms associated with testosterone deficiency (TD), many testosterone therapies (TTh) are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T...
www.excelmale.com
3.8 Oral testosterone undecanoate (TU)
Historically, oral TTh with non-esterified T has been unsuccessful in delivering physiological T due to first-pass hepatic metabolism; to overcome this, high doses were needed to achieve measurable serum T levels.86 A new, oral TU formulation delivered via a self-emulsifying drug delivery system was developed to promote solubilization and absorption of the lipophilic TU in the gastrointestinal tract, and in March 2019, became the first oral TTh approved by the FDA. In a phase 2 study, 200 mg oral TU administered twice a day resulted in 87% of men achieving average serum T levels within the physiological range (10.4–34.7 nmol/L, or 300–1,000 ng/dL), and none of the men had serum T levels >52 nmol/L (1,500 ng/dL). 87 Peak T levels were reached 4 to 5 hours after administration, and levels steadily decreased to baseline at approximately 12 hours unless a second dose was administered. As oral TU capsules are recommended to be taken with a meal, serum T levels appear to be modulated by dietary fat content. 88 Cavg and mean Cmax serum T levels were approximately 2-fold higher when 200 mg oral TU was administered with food compared with fasting. 87 Dietary fat was found to affect mean serum T levels achieved with oral TU; meals with higher fat content increased serum T concentrations. In a phase 3 study comparing the efficacy and safety of 237 mg oral TU given twice daily with once-daily 60 mg topical T solution, 87% (145/166) of men with TD treated with oral TU were able to achieve a mean Cavg within 8.7 to 31.4 nmol/L (252–907 ng/dL), meeting the primary objective.89 At the final study visit on day 105, the mean Cavg was 14.0 nmol/L (403 ng/dL) and Cmax was 34.9 nmol/L (1,008 ng/dL). As oral TU is given twice daily, there were 2 serum T peaks between 20.8 and 24.3 nmol/L (600 and 700 ng/dL) approximately 4 hours after administration, 2 sub-therapeutic troughs (<6.9 nmol/L or <200 ng/dL) 12 hours after administration, and a peak-to-trough ratio approaching 4.
4. Diurnal Variation in Serum T Levels
Diurnal variation in endogenous serum T levels in healthy men is well documented, with the highest T levels in the morning and lowest values in the afternoon and early evening, although the amplitudes of peak and trough levels vary by age. In 1983, a study by Bremner et al showed that there was a clear difference between serum T levels in normal young men (mean age 25.2 years) and older men (mean age 71.0 years).5 In young men, serum T levels were highest in the morning, falling to their lowest levels approximately 12 hours later and gradually increasing again to peak levels the next morning. Furthermore, a study to determine how endogenous T levels vary over clinic hours revealed that in 30- to 40-year-old men, morning total T levels are 30% to 35% higher than levels measured in the mid to late afternoon. This amplitude in daily endogenous T variation decreases with age, with a morning-to-afternoon difference of only 10% in 70-year-old men.90 The morning-to-afternoon total T ratios in young and older men were approximately 1.3 and 1.1, respectively, similar to what was observed in the Bremner study. These observations have led to recommendations in various clinical guidelines, including those of the American Urology Association in 2018, to obtain early morning blood tests for the diagnosis of TD, a threshold defined as <10.4 nmol/L (300 ng/dL). 3 While endogenous serum T exhibits a clear diurnal pattern in young men that appears to be blunted naturally as men age, there does not appear to be much diurnal variation for DHT, SHBG, LH, FSH, or E2, regardless of age.90
Diurnal variation appears to be absent in men with TD. Using a population mixed-effect analysis, Gupta et al showed that no circadian rhythm was detected in men with TD, and the mean endogenous T levels in men with TD (serum T levels <10.4 nmol/L, or 300 ng/dL) were much lower than in healthy young (mean age, 28 years) or older (mean age, 71 years) men. 91 Consistent with the literature, their modeling of circadian T in healthy young and older men revealed peak-to-trough ratios of 1.3 and 1.2, respectively. Additionally, univariate analysis of cross-sectional data from 3,007 older men (≥40 years) showed that the proportion of men with serum T levels <10.4 nmol/L (300 ng/dL) did not significantly change during the day (P<0.11), further supporting that endogenous T diurnal variation is absent in men with TD.92 Results from a study by Shlykova et al evaluating endogenous T levels over a 24-hour period in 21 healthy male volunteers showed that men with baseline serum T levels <10.4 nmol/L (300 ng/dL) did not demonstrate diurnal variation within the 24-hour sampling period. 93 To understand the circadian rhythmicity of T levels in men with TD, a population kinetic model built by Gonzales-Sales et al, using baseline T profiles from 859 men with TD, predicted a base T value of 8.3 nmol/L (239 ng/dL), with the amplitude of oscillation estimated to be 1.1 nmol/L (32.4 ng/dL). 94 Their model also predicted that a stretched cosine function was more suitable to describe the circadian behavior of T levels of men with TD, as trough levels occurred approximately 5 hours after peak T levels, and levels then increased until the next peak occurred approximately 19 hours later.94
*A variety of exogenous TTh are available to increase serum T to physiologic levels in males with TD and may alleviate symptoms associated with TD.2 Some T replacement options more closely mimic the circadian levels of T identified in older men, whereas other options seem to provide PK profiles closer to those of younger men (Fig. 1 [Please put figure as close as possible to this callout] and Table 1). Some TTh options provide profiles that exceed the frequency of the natural T circadian rhythmicity.
Once-weekly SC TE injections bring mean T levels into the physiologic range within 24 hours after the first dose, with a total T Cmax/Cmin ratio of 1.8. The PK profile appears to mimic the flatter profile of older males’ endogenous T.95 IM T injections can cause both supratherapeutic T levels post-injection and subtherapeutic levels during the dosing interval, and depending on the formulation and dosage, peak-to-trough ratios of IM TC and TE range between 2 and 5.3. Longer-lasting TU injections do not demonstrate the supratherapeutic peaks of other IM formulations, with trough levels occurring at later time points after each injection and a peak-to-trough ratio of approximately 2.6 to 2.8. All IM TTh preparations result in PK profiles that are unlike those of the normal diurnal variation of healthy young or older men.
Daily transdermal gels and solutions, and nasal and oral T products, provide a consistent serum T level within the physiologic range in most patients. The daily dosing frequency of the topical gel products results in a PK profile with a resemblance to that of endogenous T in younger males.
*Men using nasal and oral T products are able to achieve mean serum T levels that are within the normal range, but they experience several T peaks and troughs throughout the day because of the multiple daily dosing regimens required (2 or 3 times/day). This results in a PK profile that significantly deviates from the endogenous PK profiles of both younger and older patients.
*No single formulation appears to provide an exposure profile that would resemble diurnal variation of both young and older men.
*The importance of diurnal variation of endogenous T is not fully understood, but there may be additional factors (eg, sleep quality and duration) that may influence endogenous T levels.96 However, further clarification is needed for the association between the circadian timing of sleep loss and its effect on T levels.
Keep us updated...I am about to start a nearly identical protocol.
andrepohlann
Member
This is easy to find out. Just do not inject for a view days and see how you sleep. I am on 10mg daily. If I do not inject in the morning (so skip one day) my heart rate decreases by 5 beats or so the following night. In my opinion 14mg is high and 18 is way to high. 10 brings me to 925 total, 15 to 1300.
Or advanced: Buy a Garmin or a cheap Fitbit and track your sleep go off for 3 days and see what happens.
andrepohlann
Member
Right, I am one of the 3/4. I reduce 10mg daily to 20mg 3 times/week an see where this leeds to.
Looks like you just switched to the low dose daily a few weeks ago and you're already feeling good - did you feel like garbage the first week or two?
I posted this thread and ended up not checking it for a bit. I've been doing 18mg a day recently (no AI or HCG) and I feel pretty damn good.
I'm also on the Carnivore MD diet (fruit and meat only ... little bit of dairy) and i feel awesome.
Sleep is still hit and miss, I slept great last night and didn't have many carbs before bed so it could be an insulin spike that has been waking me up?
Because usually ill eat a ton of carbs at bed and while i think it helps me get to sleep, it also wakes me up after 4 or 5 hours...just a theory.
Going to get blood work soon and i will report back. 18mg daily seems to be best for my anxiety, stable mood, etc out of any protocol i have tried.
I'm also on the Carnivore MD diet (fruit and meat only ... little bit of dairy) and i feel awesome.
Sleep is still hit and miss, I slept great last night and didn't have many carbs before bed so it could be an insulin spike that has been waking me up?
Because usually ill eat a ton of carbs at bed and while i think it helps me get to sleep, it also wakes me up after 4 or 5 hours...just a theory.
Going to get blood work soon and i will report back. 18mg daily seems to be best for my anxiety, stable mood, etc out of any protocol i have tried.
As far as diet and sleep goes, I’ve seen multiple people that track their sleep report that the earlier they stop eating, the better their sleep is. I remember a guy tracked his sleep very thoroughly, and he saw pretty big improvements going from having his last meal at 9pm, to having his last meal at 6pm. His sleep scores were all much better when he stopped eating at 6pm. And there’s a bunch of studies at this point showing that when u stop eating at least 2-3 hours before bed that it significantly decreases ur risk of Alzheimer’s/ dementia. I know I personally always sleep better when I stop eating at around 7-9pm, and get to bed usually around 11pm.
Ur definitely on the right track diet wise. I try to follow a diet as close to Paul Saladino as I can. I sleep great. But I also do a ton of other things to optimize my health, so it’s hard to say what’s contributing the most to me sleeping so well. I think that when u give the body everything it needs, and it’s optimized, everything just works how it should, and it’s never one or two things that are responsible. But if I had to pick one thing to improve sleep, it would probably be magnesium. I personally use liquid magnesium chloride, specifically the brand Remag. If ur not already taking high dose magnesium from a quality source, I would get on that asap. I take literally as much as I can tolerate before getting loose bowels. The more the better with magnesium, ime. Best way to dose it, imo, is to find the highest dose u can tolerate without getting loose bowels
I personally have only ever done IM. Been injecting EOD for around 7 years now. The last 2-3 years been on nandrolone and test so been doing 2 IM injections EOD. Did ED injections for about 3 months one time, but didn’t notice any benefits over EOD. I’ve always injected into the outter part of my thighs. Have always used a 27 garage insulin syringe to inject. The injections don’t bother me a bit. I’m a nurse tho, so maybe that’s why they don’t bother me, not sure. But I can easily inject IM like this for the rest of my life. Just becomes habit like going to work or eating after a while
But why? Mix them
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