Testing Test Talk

[Calm Logic]

My internist told me yesterday to raise my dose of tirz to 15 mg since that will help with my concern about low TST levels (since greater weight loss will help raise TST more).

Regarding lab values for testosterone in obese men:

Also most obese folks have low total testosterone. So every research study will have a low total testosterone patient if obese. A total testosterone means nothing in an obese patient . A free/ bioavailable is better. Low total testosterone in the obese doesn’t mean they need replacement.

Elaboration by Google Gemini:

Let's break down why total testosterone can be misleading in this population and why free or bioavailable testosterone is often a better indicator.

Why Total Testosterone is Misleading in Obese Individuals​

1. Increased Sex Hormone-Binding Globulin (SHBG):
   • Obesity, particularly visceral obesity (fat around the organs), is associated with lower levels of SHBG.
   • SHBG is a protein produced by the liver that binds to sex hormones, including testosterone, estrogen, and DHT. When testosterone is bound to SHBG, it's largely inactive and unavailable to tissues.
   • Counterintuitively, while you might expect lower SHBG to mean more free testosterone, the overall hormonal milieu in obesity often leads to a complex interplay.
2. Increased Aromatase Activity:
   • Adipose tissue (fat cells) contains an enzyme called aromatase.
   • Aromatase converts androgens (like testosterone) into estrogens (like estradiol).
   • In obese individuals, especially those with a large amount of adipose tissue, there's increased aromatase activity. This means more testosterone is being converted into estrogen, leading to lower total testosterone levels and potentially higher estrogen levels. Higher estrogen can also feedback to the brain and further suppress testosterone production.
3. Insulin Resistance and Inflammation:
   • Obesity is often accompanied by insulin resistance and chronic low-grade inflammation.
   • These factors can directly impact the hypothalamic-pituitary-gonadal (HPG) axis, which regulates testosterone production. Insulin resistance can impair Leydig cell function in the testes, and inflammation can suppress GnRH (gonadotropin-releasing hormone) and LH (luteinizing hormone) secretion from the brain, leading to reduced testosterone synthesis.

Why Free/Bioavailable Testosterone is Better​

Given the factors above, here's why free and bioavailable testosterone provide a more accurate picture:

1. Free Testosterone: This is the portion of testosterone that is not bound to SHBG or albumin. It's the biologically active form that can readily enter cells and exert its effects.
2. Bioavailable Testosterone: This includes free testosterone plus testosterone loosely bound to albumin. Testosterone bound to albumin can also dissociate and become available to tissues. Testosterone bound tightly to SHBG is generally not considered bioavailable.

By measuring free or bioavailable testosterone, clinicians can get a better sense of how much testosterone is actually available to the body's tissues, regardless of the total amount or SHBG levels.

Why Low Total Testosterone in Obese Individuals Doesn't Automatically Mean They Need Replacement​

This is the crucial point you've made. Here's why:

1. The Root Cause is Often Obesity Itself:
   • The low total testosterone in obese individuals is often a consequence of their obesity (increased aromatase, altered SHBG, insulin resistance, inflammation).
   • Simply giving exogenous testosterone without addressing the underlying obesity is like treating a symptom without addressing the disease.
2. Benefits of Weight Loss:
   • Numerous studies have shown that significant weight loss (through lifestyle changes, bariatric surgery, or medication) can lead to a substantial increase in endogenous testosterone levels in obese men.
   • Weight loss reduces adipose tissue (less aromatase), improves insulin sensitivity, and decreases inflammation, all of which can restore normal HPG axis function.
3. Potential Risks of Unnecessary Testosterone Replacement:
   • Giving testosterone to someone whose low levels are primarily due to obesity can suppress their natural testosterone production even further.
   • Long-term testosterone replacement carries its own risks, including cardiovascular issues (though this is debated and complex), erythrocytosis (increased red blood cell count), prostate issues, and suppression of fertility.

Clinical Implications​

• Comprehensive Evaluation: When an obese patient presents with symptoms of hypogonadism (fatigue, low libido, erectile dysfunction, depression, etc.) and low total testosterone, a clinician should always measure free or bioavailable testosterone.
• Focus on Lifestyle Intervention: The primary recommendation for obese individuals with low testosterone should almost always be aggressive weight loss and lifestyle modification. This addresses the root cause and often resolves the testosterone deficiency naturally.
• Careful Consideration for Replacement: Testosterone replacement therapy might be considered in obese individuals only after a thorough evaluation, including confirmation of consistently low free/bioavailable testosterone, a comprehensive discussion of risks and benefits, and often after attempts at weight loss have been insufficient to normalize levels or alleviate symptoms.

 

[hexagonal]

The problem is that even with significant weight loss, most people don't see that significant of a bump in their total testosterone.

Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis - PMC

Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. ...

pmc.ncbi.nlm.nih.gov

https://www.nature.com/articles/s41366-024-01591-7 - 40kg of weight loss will only get you a 24% boost in total test!

The better off you are initially the better your results will be losing weight, but if you are already quite low, the returns just aren't going to be all that good.

Meanwhile, we know that TRT actively helps with weight loss in hypogonadal men:

https://www.liebertpub.com/doi/10.1089/andro.2020.0010

Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies - International Journal of Obesity

Long-term testosterone replacement therapy (TRT) up to 5 years has been shown to produce progressive and sustainable weight loss (WL) in hypogonadal men. This study investigated effects of long-term TRT up to 8 years in hypogonadal men with different obesity classes. From two independent...

www.nature.com

Some of the Gemini answer is nonsense, too.

Giving testosterone to someone whose low levels are primarily due to obesity can suppress their natural testosterone production even further.

If Gemini can't even get this right it isn't pulling in correct data to begin with. It's not a "can" - it's a 100% will. You will not produce natural testosterone when on TRT. Exogenous androgens shut down the HPTA and testosterone production stops. But you're on exogenous test, so... who cares?

Long-term testosterone replacement carries its own risks, including cardiovascular issues (though this is debated and complex)

TRAVERSE disagrees. The largest and longest running study on the cardiovascular safety of TRT.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Free and bioavailable T are important metrics for anyone and everyone, not just obese people, but your body uses the bound testosterone for things too, so the idea that total test can just be ignored doesn't make much sense.


The idea of going back to being hypogonadal just because I might maybe get within spitting distance of the bottom of the reference range after a year+ of losing weight is so ludicrous (and frankly, terrifying, after seeing how much QOL improvement I have had moving towards the upper quarter of the reference range) to me that I would immediately be talking to another doctor about it if that was the response I had gotten. And I saw continual improvement on my symptoms as I moved up through the range dialing in the dosage - even going from 600s to 700s had marked improvement, though things seem to have taper off around there and higher levels did not make much difference on symptoms.

Yes, you should research things before you make a decision. There's a lot to keep in mind. And yes, you will likely need to do it for life, though most people can come off of TRT and resume their original (shitty) production... But many people here are happy to talk about being on a GLP-1 for life.

 

[Revo39564]

The problem is that even with significant weight loss, most people don't see that significant of a bump in their total testosterone.

Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis - PMC

Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality. Examine the direction and causality of the relationship between body mass index (BMI) and serum testosterone. ...

pmc.ncbi.nlm.nih.gov

https://www.nature.com/articles/s41366-024-01591-7 - 40kg of weight loss will only get you a 24% boost in total test!

The better off you are initially the better your results will be losing weight, but if you are already quite low, the returns just aren't going to be all that good.

Meanwhile, we know that TRT actively helps with weight loss in hypogonadal men:

https://www.liebertpub.com/doi/10.1089/andro.2020.0010

Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies - International Journal of Obesity

Long-term testosterone replacement therapy (TRT) up to 5 years has been shown to produce progressive and sustainable weight loss (WL) in hypogonadal men. This study investigated effects of long-term TRT up to 8 years in hypogonadal men with different obesity classes. From two independent...

www.nature.com

Some of the Gemini answer is nonsense, too.


If Gemini can't even get this right it isn't pulling in correct data to begin with. It's not a "can" - it's a 100% will. You will not produce natural testosterone when on TRT. Exogenous androgens shut down the HPTA and testosterone production stops. But you're on exogenous test, so... who cares?


TRAVERSE disagrees. The largest and longest running study on the cardiovascular safety of TRT.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

Free and bioavailable T are important metrics for anyone and everyone, not just obese people, but your body uses the bound testosterone for things too, so the idea that total test can just be ignored doesn't make much sense.


The idea of going back to being hypogonadal just because I might maybe get within spitting distance of the bottom of the reference range after a year+ of losing weight is so ludicrous (and frankly, terrifying, after seeing how much QOL improvement I have had moving towards the upper quarter of the reference range) to me that I would immediately be talking to another doctor about it if that was the response I had gotten. And I saw continual improvement on my symptoms as I moved up through the range dialing in the dosage - even going from 600s to 700s had marked improvement, though things seem to have taper off around there and higher levels did not make much difference on symptoms.

Yes, you should research things before you make a decision. There's a lot to keep in mind. And yes, you will likely need to do it for life, though most people can come off of TRT and resume their original (shitty) production... But many people here are happy to talk about being on a GLP-1 for life.

Obese folks will aromatize the testosterone into estrogen. Weight loss of course helps this. Total testosterone isn’t that helpful in diagnosing hypogonadism in the obese. Smarter for the obese to take a small dose of an aromatase inhibitor when weight normal taper off

 

[hexagonal]

Obese folks will aromatize the testosterone into estrogen. Weight loss of course helps this. Total testosterone isn’t that helpful in diagnosing hypogonadism in the obese. Smarter for the obese to take a small dose of an aromatase inhibitor when weight normal taper off

I started on testosterone while obese. Yes, some portion of my testosterone aromatized, but total testosterone was still a very useful metric that correlated directly with symptom relief.

I don't understand why you think that some aromatization suddenly means one of the primary blood markers for the hormone is suddenly irrelevant.

If you need an AI, sure, take an AI. But that's more about looking at your estrogen levels and symptoms than something that should make you discount your total test.

 

[Revo39564]

I started on testosterone while obese. Yes, some portion of my testosterone aromatized, but total testosterone was still a very useful metric that correlated directly with symptom relief.

I don't understand why you think that some aromatization suddenly means one of the primary blood markers for the hormone is suddenly irrelevant.

If you need an AI, sure, take an AI. But that's more about looking at your estrogen levels and symptoms than something that should make you discount your total test.

Don’t need AI I have prescribed testosterone almost 20 years and have seen the huge spikes in estradiol and many negative side effects . Many providers don’t know how to treat it properly. an aromatase inhibitor with or without testosterone can raise testosterone very well Total testosterone can be good to monitor treatment for obese once it is diagnosed appropriately.

 

[hexagonal]

Don’t need AI I have prescribed testosterone almost 20 years and have seen the huge spikes in estradiol and many negative side effects . Many providers don’t know how to treat it properly. an aromatase inhibitor with or without testosterone can raise testosterone very well Total testosterone can be good to monitor treatment for obese once it is diagnosed appropriately.

Taking an AI would have done nothing positive for me before I was on TRT. My e2 levels were already in reference range. Why would I want to risk crashing my e2? Even outside of the huge impact to mood, why do I want to go to unhealthy levels of something that is neuro and cardio protective? Add in the fact that AIs can impact lipids and blood pressure negatively, potentially cause bone density loss... I've done my best to find a balance between symptom relief and needing to take an AI at all on TRT because I want to avoid taking one if at all possible.

It's very strange to me that you're suggesting an AI as a first line of treatment, when all three doctors I discussed TRT with were adamant that minimizing their use was ideal from a health perspective.

 

[Revo39564]

Taking an AI would have done nothing positive for me before I was on TRT. My e2 levels were already in reference range. Why would I want to risk crashing my e2? Even outside of the huge impact to mood, why do I want to go to unhealthy levels of something that is neuro and cardio protective? Add in the fact that AIs can impact lipids and blood pressure negatively, potentially cause bone density loss... I've done my best to find a balance between symptom relief and needing to take an AI at all on TRT because I want to avoid taking one if at all possible.

It's very strange to me that you're suggesting an AI as a first line of treatment, when all three doctors I discussed TRT with were adamant that minimizing their use was ideal from a health perspective.

Not sure didn’t see your bloodwork . I usually use endocrinologist guidelines, not family doctor or anything like that. most of times I can tell if you’re truly hypogonadal without any blood work too.

 

[Revo39564]

Taking an AI would have done nothing positive for me before I was on TRT. My e2 levels were already in reference range. Why would I want to risk crashing my e2? Even outside of the huge impact to mood, why do I want to go to unhealthy levels of something that is neuro and cardio protective? Add in the fact that AIs can impact lipids and blood pressure negatively, potentially cause bone density loss... I've done my best to find a balance between symptom relief and needing to take an AI at all on TRT because I want to avoid taking one if at all possible.

It's very strange to me that you're suggesting an AI as a first line of treatment, when all three doctors I discussed TRT with were adamant that minimizing their use was ideal from a health perspective.

Any treatment plans should be based on physical assessment and bloodwork. There’s no one-size-fits-all if you have high estradiol. Surely don’t need any testosterone to raise it higher that be crazy.

 

[Calm Logic]

I think a lot of docs shy away from TRT since it is a controlled substance and don't want to deal with the bullies at the DEA.

 

[hexagonal]

Any treatment plans should be based on physical assessment and bloodwork. There’s no one-size-fits-all if you have high estradiol. Surely don’t need any testosterone to raise it higher that be crazy.

If my testosterone levels are in the toilet my primary concern is getting them out of the toilet and figuring out the downstream effects from there.

I'm glad the doctors I have gone through have not approached the problem the way you are suggesting, because TRT has been as life-altering in a positive manner for me as GLP-1 medications have.

 

[Revo39564]

If my testosterone levels are in the toilet my primary concern is getting them out of the toilet and figuring out the downstream effects from there.

I'm glad the doctors I have gone through have not approached the problem the way you are suggesting, because TRT has been as life-altering in a positive manner for me as GLP-1 medications have.

I have seen great benefits from TRT but also an equal amount of great harm. Unfortunately many providers check one total testosterone on a patient in the late afternoon and dx hypogonadism. Heck many providers don’t even warn patients about the sterility and other risk.

 

[Revo39564]

I think a lot of docs shy away from TRT since it is a controlled substance and don't want to deal with the bullies at the DEA.

TRT is easy to prescribe.. imho. . I’ve had more difficulty with glp’s and crazy rules and shortages

 

[Calm Logic]

I would have walked out yesterday with a prescription for TRT, but my scaredy-cat doc doesn't prescribe any controlled substances. I didn't tell him I already have vials of test-e already from India, which will have to continue to be my source.

 

[Revo39564]

I would have walked out yesterday with a prescription for TRT, but my scaredy-cat doc doesn't prescribe any controlled substances. I didn't tell him I already have vials of test-e already from India, which will have to continue to be my source.

Gotta get a good internal med doc.. love my DO…… he knows where I get my glp’s lol…… down 195 lbs

 

[AndyPanda]

I would have walked out yesterday with a prescription for TRT, but my scaredy-cat doc doesn't prescribe any controlled substances. I didn't tell him I already have vials of test-e already from India, which will have to continue to be my source.

A doctor who is that narrow minded should not even be practicing medicine. That’s like saying “I’m a mechanic, but don’t use screwdrivers.”

 

[Revo39564]

A doctor who is that narrow minded should not even be practicing medicine. That’s like saying “I’m a mechanic, but don’t use screwdrivers.”

Wonder if he couldn’t prescribe scheduled meds? Some might be on drug diversion ?

 

[Calm Logic]

Yeah, I will try another internist. I don't see any criminal records, but the AZ medical board had him on probation for a year, which just ended earlier this month. There were at least several patient cases where there were issues, including providing less than the standard of care.

Regarding controlled substances, he prescribed a patient a higher dose of clonazepam than currently prescribed by the patient's psychiatrist, without consulting the psychiatrist at any point or documenting the rationale.

 

[AndyPanda]

I don't see any criminal records, but the AZ medical board had him on probation for a year, which just ended earlier this month. There were at least several patient cases where there were issues, including prescribing a patient a higher dose of clonazepam than currently prescribed by the patient's psychiatrist.

Benzodiazepines are a far cry from testosterone. It’s kind of amusing. When I was in Sedona a few years ago there must have been 5 different clinics peddling ketamine therapy.

 

[Calm Logic]

Regarding Sedona, I also like the views from the old mining town of Jerome, which is nearby. I don't like Flagstaff much, except for the indigenous museum.

 

[Revo39564]

Yeah, I will try another internist. I don't see any criminal records, but the AZ medical board had him on probation for a year, which just ended earlier this month. There were at least several patient cases where there were issues, including providing less than the standard of care.

Regarding controlled substances, he prescribed a patient a higher dose of clonazepam than currently prescribed by the patient's psychiatrist, without consulting the psychiatrist at any point or documenting the rationale.

Would make sense that he would be afraid to prescribe a controlled substance…… surprised they cared about klonopin

 

[AndyPanda]

Regarding Sedona, I also like the views from the old mining town of Jerome, which is nearby. I don't like Flagstaff much, except for the indigenous museum.

Jerome is a creepy little place. Lol. The lead singer from Tool lives there. Has a winery called Merkin Vineyards and a record shop.