Advice on next steps - mid-low free T

[metflex]

Advice on next steps — mid-low free T? I'm a doctor who does a fair amount of hypogonadism management but looking for some insight given my age and circumstances of normal TT but low normal Free T.

Body:
Age 30, 6’3”, 196 lbs, ~14% body fat by BIA. Train 4–5x/wk (resistance + cardio), Mediterranean-style diet, low alcohol (1–2 drinks/week), no processed foods, ~2600-2800 kcal/day, 160-180 g protein. Supplements: creatine, beta-alanine, omega-3s, MV.

Symptoms: mild fatigue, irritability/mild anhedonia, low libido, reduced orgasm intensity, slower recovery after training. No ED, notable joint pain.

Labs:

• Total T: 614 ng/dL
• Free T: 10.4 ng/dL (20-25th percentile for age)
• SHBG: 47
• DHEA-S: 83.4 ug/dL
• Estradiol: 37.9 pg/mL
• TSH 2.6
• CRP: 0.7
• A1c: 5.4
• Insulin: 2.6

Leaning toward trying enclomiphene or hCG monotherapy first before considering Kyzatrex or TRT. → Goal is to improve free T and DHEA-S. Already have 4 kids so not an issue of infertility.

Would appreciate input —

• Would you even consider increasing T levels?
• What protocols/doses are guys having success with in similar situation?
• Enclo vs hCG first?
• Thoughts on going straight to something like Kyzatrex

Thanks in advance for any advice — looking to optimize long term not just quick fix.

 

[Cataceous]

It's less common to have low-T symptoms with that level of free testosterone. I would steer you away from the three treatment options you're considering. They all come with some risk of doing more harm than good given that you're not firmly into hypogonadal territory. If you want to explore raising testosterone in a safer manner then you might consider trying short-acting testosterone. The readily available forms are testosterone nasal gel or testosterone buccal troches. The short duration of action reduces the level of interference with other hormones. Yet the clinical trials for Natesto demonstrate that this pulsatile delivery can resolve low-T symptoms. If you don't see improvements then you would need to consider that low testosterone is not the cause of your issues.

You can easily raise DHEA-S with an inexpensive oral supplement. For example, I've been taking a quarter tablet of this one twice a day for about 10 years to consistently raise DHEA-S by about 150 µ/dL.

 

[metflex]

Thanks for your thoughts here. Do you know how the pharmacokinetics of Natesto compare to Kyzatrex?

 

[Cataceous]

As I recall, all of the oral forms of testosterone have considerably longer half-lives than the nasal gels. Something like a few hours versus less than an hour. This makes the difference between significant and possibly complete suppression of the HPTA, versus relatively minor suppression. Over the years I have become increasingly convinced that there are some nontrivial concerns about long-term HPTA suppression. For example, GnRH is known to have additional functions.

 

[Systemlord]

Thanks for your thoughts here. Do you know how the pharmacokinetics of Natesto compare to Kyzatrex?

I’ve been on both and my experience on oral testosterone is much better than any other formulation. Natesto benefits were very short-lived, a half an hour after each dose benefits waned.

I stopped Jatenzo (competing brand to Kyzatrex) more than eight months ago and my HPTA fired back up after a week. I’m considering restarting.

Natesto info is detailed (PK profiles) in the first few posts in the linked thread below.

Thread 'My Experience On Jatenzo (Oral TRT) Log'

Jun 16, 2021

I wanted to start a thread detailing my personal experience with Jatenzo (oral TRT) which is remarkable in how quickly it has shown results when compared with injections. The first week on Jatenzo was very pleasant unlike my experience after dosing changes on injections, all with minimal swings and I felt things stabilize on day 7 which is where things felt consistent.

The first few days on Jatenzo my glucose levels were the lowest, then over the next two and a half weeks I would see glucose levels fluctuate wildly and at the end of week three a return to those same lower fasting and...

• Systemlord
• jatenzo oral testosterone
• Replies: 374
• Forum: Testosterone Basics & Questions

• 

 

[FunkOdyssey]

As I recall, all of the oral forms of testosterone have considerably longer half-lives than the nasal gels. Something like a few hours versus less than an hour. This makes the difference between significant and possibly complete suppression of the HPTA, versus relatively minor suppression.

We have data showing no statistically significant suppression with once daily oral testosterone at Maximus which will be published soon on the website. The shorter half-life of bioidentical oral testosterone vs. testosterone undecanoate is likely responsible. Please see attached excerpts.

 

[FunkOdyssey]

• Would you even consider increasing T levels?
• What protocols/doses are guys having success with in similar situation?
• Enclo vs hCG first?
• Thoughts on going straight to something like Kyzatrex

I'll give you my less conservative perspective. Yes, I would experiment with increasing T levels, given your symptoms, which would produce a positive result on the ADAM questionnaire. Your levels, while not low, are not high enough to rule out the possibility that more T could improve the situation. Additionally, the long-term risks associated with everything you are considering trying is very low.

Among the options presented, enclomiphene is less likely to be helpful with low libido than either hCG monotherapy or oral testosterone. I'm not a big fan of the way hCG turns you into an estrogen factory, and given your baseline T/E2 ratio is skewed somewhat estrogenic, that might not do you any favors. Oral testosterone, uniquely among TRT modalities, actually reduces E2 slightly, and the elevated DHT it produces can be very helpful with sexual symptoms. That would be my preference in this scenario.

Interestingly, oral testosterone can dramatically increase DHEA-S levels based on our internal data. We don't understand the mechanism yet, but that might be another reason to consider it in your case.

Also, if you haven't experimented with stopping the fish oil supplementation, I would suggest trying that at some point. A minority of men experience reduced libido and depressed mood with fish oil, which you will discover with a Reddit search. I am one of them; perhaps you are also. I would give the multivitamin the same scrutiny, with a trial stoppage to ensure that is not having a negative effect.

 

[FunkOdyssey]

Just curious: how did you manage to have four kids by age 30, having been in med school and residency the entire time? I feel like there's a story there.

 

[metflex]

I'll give you my less conservative perspective. Yes, I would experiment with increasing T levels, given your symptoms, which would produce a positive result on the ADAM questionnaire. Your levels, while not low, are not high enough to rule out the possibility that more T could improve the situation. Additionally, the long-term risks associated with everything you are considering trying is very low.

Among the options presented, enclomiphene is less likely to be helpful with low libido than either hCG monotherapy or oral testosterone. I'm not a big fan of the way hCG turns you into an estrogen factory, and given your baseline T/E2 ratio is skewed somewhat estrogenic, that might not do you any favors. Oral testosterone, uniquely among TRT modalities, actually reduces E2 slightly, and the elevated DHT it produces can be very helpful with sexual symptoms. That would be my preference in this scenario.

Interestingly, oral testosterone can dramatically increase DHEA-S levels based on our internal data. We don't understand the mechanism yet, but that might be another reason to consider it in your case.

Also, if you haven't experimented with stopping the fish oil supplementation, I would suggest trying that at some point. A minority of men experience reduced libido and depressed mood with fish oil, which you will discover with a Reddit search. I am one of them; perhaps you are also. I would give the multivitamin the same scrutiny, with a trial stoppage to ensure that is not having a negative effect.

Thank you for this @FunkOdyssey! I appreciate the thoughts. My idea is to do a trial of something that has a high degree of certainty of increasing levels just to see if it improves anything. My thoughts are to get free T up safely somewhere in the range of 15 ng/dL but open for feedback here? As far as med school - yeah 2 kids in school and 1 as soon as I graduated - we didn't waste any time haha. As far as dosing; you thinking hCG 250IU twice weekly and kyzatrex 100mg in morning only (to error on lesser dose)?

 

[FunkOdyssey]

As far as dosing; you thinking hCG 250IU twice weekly and kyzatrex 100mg in morning only (to error on lesser dose)?

hCG will only complicate things - I would leave that out (at least initially). I work for Maximus so my bias is towards our oral testosterone, but with Kyzatrex, you will need much higher doses than 100 mg to move the needle. 200 mg bid only produced 14 ng/dL free T in their phase 3 trial. You'd probably want at least 300 mg to make a real difference here.

 

[metflex]

hCG will only complicate things - I would leave that out (at least initially). I work for Maximus so my bias is towards our oral testosterone, but with Kyzatrex, you will need much higher doses than 100 mg to move the needle. 200 mg bid only produced 14 ng/dL free T in their phase 3 trial. You'd probably want at least 300 mg to make a real difference here.

Interesting! If I understand you correctly, since my total levels are already normal, I would need higher oral dose to increase both endogenous/exogenous levels? What form of oral do you guys use at maximus? can you share the data on oral increasing free T levels at given doses? I cannot find

 

[FunkOdyssey]

If I understand you correctly, since my total levels are already normal, I would need higher oral dose to increase both endogenous/exogenous levels?

In the kyzatrex trial I mentioned, they started at 7 ng/dL free T and increased by 7 ng/dL to 14 ng/dL with the 200 mg bid dose. I would be looking to create a dramatic difference from your 10 ng/dL baseline with this experiment to ensure the results are noticeable, and targeting something more like 20 ng/dL free T. I'm not sure where your personal comfort zone is with levels, but bear in mind we're measuring this at peak with oral T, while many doing well on injectable TRT are troughing significantly higher than that.

 

[FunkOdyssey]

What form of oral do you guys use at maximus?

Compounded bioidentical / native testosterone in a lipid-based delivery vehicle, similar in that respect to Kyzatrex and the other oral TU products. The bioidentical testosterone is better tolerated than TU with fewer gastrointestinal side effects, and appears to be less suppressive of the HPT axis as well.

 

[Cataceous]

We have data showing no statistically significant suppression with once daily oral testosterone at Maximus which will be published soon on the website. The shorter half-life of bioidentical oral testosterone vs. testosterone undecanoate is likely responsible. Please see attached excerpts.

That's good to know and nice work by Maximus. It sounds like I may be able to add it to the list of short-acting testosterone treatments. I still don't like the use of the term "bioidentical" to differentiate it from products that in the end also yield bioidentical testosterone. "Non-esterified" would be more honest, but possibly off-putting to the potential customers.

.... Additionally, the long-term risks associated with everything you are considering trying is very low.
...

The problem is that we don't know that for a fact. For differing reasons, any of these treatments could be significantly increasing the risk of dementia later in life. I hope not, but hope alone is not grounds for dismissing the risk in the absence of any quantitation.