Why do some men need supraphysiological doses of testosterone to achieve normal levels

[Gianluca]

Considering the daily natural production of a healthy young male, you would think that if someone inject 100mg tot weekly either using a daily or EOD protocol with an ester like Cypionate, we would see both TT and FT above range, theoretically.

However, people like me: for example I inject 20mg daily, and my levels are TT 5/600 with a FT of 19/20, it doesn't make sense then right?

What I think is happening:

Low SHBG can play a role potentially converting fast Test into metabolites. Testosterone itself can also be metabolized fast. Since we inject the testosterone I do not think we can talk about absorption loss, especially with IM injection. Yet, the "loss" seem to be super fast. I inject at 7am and a couple of hours after when I pull my blood the testosterone already disappeared before it peaks?

@Cataceous @madman what else do you guys think is happening?

 

[Vince]

Considering the daily natural production of a healthy young male, you would think that if someone inject 100mg tot weekly either using a daily or EOD protocol with an ester like Cypionate, we would see both TT and FT above range, theoretically.

However, people like me: for example I inject 20mg daily, and my levels are TT 5/600 with a FT of 19/20, it doesn't make sense then right?

What I think is happening:

Low SHBG can play a role potentially converting fast Test into metabolites. Testosterone itself can also be metabolized fast. Since we inject the testosterone I do not think we can talk about absorption loss, especially with IM injection. Yet, the "loss" seem to be super fast. I inject at 7am and a couple of hours after when I pull my blood the testosterone already disappeared before it peaks?

@Cataceous @madman what else do you guys think is happening?

Are you a fast metabolizer of medicines? - Excel Male TRT Forum

Differences in your DNA that make up the CYP2D6 gene can change how well you are able to break down certain medicines. If you break down a medicine too fast or too slowly, this may cause a bad reaction to the medicine. By testing your DNA (with a pharmacogenetic test), we may find DNA...

www.excelmale.com

 

[Vince]

CYP17A1: This gene plays a role in the synthesis of testosterone.

 

[Cataceous]

Considering the daily natural production of a healthy young male, you would think that if someone inject 100mg tot weekly either using a daily or EOD protocol with an ester like Cypionate, we would see both TT and FT above range, theoretically.
...

In fact this is usually the case. 100 mg per week in divided doses puts my total testosterone over 1,200 ng/dL, and this is common. @Readalot shared data supporting this proposition.

...
However, people like me: for example I inject 20mg daily, and my levels are TT 5/600 with a FT of 19/20, it doesn't make sense then right?
...

Your low SHBG suppresses total testosterone. Free testosterone is proportional to the dose rate. By what method are you determining free testosterone? I hope it's not via the useless direct method. What is calculated free testosterone?

...
Low SHBG can play a role potentially converting fast Test into metabolites. Testosterone itself can also be metabolized fast. Since we inject the testosterone I do not think we can talk about absorption loss, especially with IM injection. Yet, the "loss" seem to be super fast. I inject at 7am and a couple of hours after when I pull my blood the testosterone already disappeared before it peaks?
...

The metabolic clearance rate of testosterone is determined by liver function and by the level of free testosterone. SHBG has very little to do with it. Furthermore, more effective liver function proportionally reduces free testosterone; it does not affect the apparent half-life of testosterone esters. The half-life is tied to the drop in serum testosterone over time. While most men injecting testosterone cypionate daily will see pretty steady serum testosterone, I have seen exceptions, men who appear to be fast absorbers. In these cases the apparent half-life of cypionate is considerably reduced; they do see unusually large drops over the course of a day.

 

[Vince]

AI Overview
Based on the provided search results, the

UGT2B17 gene plays a significant role in testosterone metabolism and clearance, specifically through glucuronidation, a process that makes testosterone easier to excrete.
Individuals with a deletion in the UGT2B17 gene show reduced glucuronidation of testosterone and therefore lower levels of testosterone glucuronide in their urine. This suggests that reduced activity of the UGT2B17 enzyme can lead to potentially higher testosterone levels due to slower clearance from the body.
Other genes are also involved in testosterone metabolism and synthesis, including:

• CYP17A1: Crucial for the production of testosterone and other steroid hormones.
• SHBG: Influences how testosterone is transported and made available in the bloodstream.
• CYP19A1 (aromatase): Converts testosterone to estrogen.
• SRD5A2: Converts testosterone to the more potent androgen, DHT.

However, the UGT2B17 gene deletion is directly linked to the rate at which testosterone is cleared from the body.



Genetic and phenotypic variation in UGT2B17, a testosterone-metabolizing ...
Abstract * Objective. A number of candidate gene and genome-wide association studies have identified significant associations between single nucleotide polymorp...

National Institutes of Health (NIH) (.gov)

UGT2B17

 

[Nelson Vergel]

Thread 'Heavier Men May Require Higher TRT Doses'

Jun 6, 2020

We finally have a study that looked at this common question.

Effect of Weight on Serum Testosterone Levels with Subcutaneous Testosterone Enanthate in Men with Testosterone Deficiency

Introduction

Obesity is a common issue among men and is often associated with low testosterone (T) levels. This association complicates the management of testosterone deficiency (hypogonadism) in overweight and obese individuals. It is known that men with a higher body mass index (BMI) need higher doses of transdermal testosterone therapy (TTh), like T 2% gel, to get their T levels back to normal...

• Nelson Vergel
• trt dose weight
• Replies: 38
• Forum: Testosterone Basics & Questions

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