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It would be very helpful to the TRT community to have a better understanding of the pharmacokinetics of TNE. Our best guess is that TNE is not as fast acting as nasal gels and buccal troches. This could make it comparable to some of the oral formulations. In any case, it would be great to have...

The direct free testosterone test correlates poorly with better methods and should not be used. Nonetheless, the Vermeulen free testosterone calculation also points to lowish numbers. Your total testosterone is artificially boosted by your highish SHBG, and therefore is not useful as an...

Evidence? For what it's worth, ChatGPT agrees with me. Reference ranges are supposed to be representative of the healthy portion of the subject population, not the entire population. Identifying who is healthy is the tricky part. 4. Challenges in Establishing Normal Ranges: Finding a truly...

There are not rigorous studies comparing the protocols, so we're relying on educated guesswork. Most likely any reasonable protocol will work when given enough time. But that includes no treatment as well, since most men do recover eventually. It's reasonable to suspect that hCG is useful...

With those numbers I wouldn't bother switching to exogenous FSH. It seems doubtful it would help. If you've seen the research then you know that the time to return of spermatogenesis is highly variable. If I'm remembering correctly, some men didn't see it until well into the second year...

This is a mistaken belief, but a common one. SHBG has very little to do with the metabolism of testosterone, which occurs primarily in the liver. SHBG is basically a storage reservoir for testosterone. If you have less of it then you cannot store as much testosterone, which lowers total...

"Jiving" is a bastardization of "jibing". jibe 2 | jīb | verb [no object] North American English informal be in accord; agree: the verdict does not jibe with the medical evidence. Been around awhile too. jive 3 [no object] US English informal be in accord; agree: her facial expressions did...

Assuming these are trough measurements, one possibility is that you absorb your TE faster than average. The implication is that your serum testosterone goes very high in the day after the injection, but then decreases relatively rapidly. The solution is to inject more often, at least every other...

If you search you'll find a lot of discussion of the relative merits of immunoassay (non-sensitive) and LC/MS (sensitive) estradiol tests. In a nutshell, the so-called sensitive tests are particularly useful if you want to quantify estradiol that is under ~5 pg/mL or so, which is about the lower...

If you're interested in the details, here's the study containing the graph. They say: Modeling the free E2 vs. free testosterone and free DHT vs. free testosterone relationships showed that our data are consistent with Michaelis-Menten enzyme kinetics in both cases...

If you switch to conventional TRT—including injections or topical gels—then there's little point in continuing with enclomiphene. Your HPTA will still end up suppressed. There are alternatives that keep things going. The most proven is testosterone nasal gel (TNG). Even without enclomiphene it...

Ignore naysayers and give it a try. The lower dose is still giving you as much or more testosterone than the average healthy young guy makes. Just be aware of a transition period in which your body adapts to the new dose. I'm doing great on the equivalent of 5.25 mg TP daily. This wouldn't be...

It’s not quite as off-the-wall as it sounds. We know that as serum testosterone increases the 5α-reductase enzyme starts to saturate, leading to a reduced efficiency in DHT creation, illustrated thusly: Even so, with high testosterone a lack of DHT is not going to be a problem; there’s still...

I agree with @madman that this cookie-cutter protocol is far from ideal. Even less so with a possible diagnosis of primary hypogonadism. I am disappointed in Defy for prescribing it. There is an alternative treatment approach that may be better for your overall health than the current blast with...

It seems to help in some cases, likely due to increased variation in serum testosterone. However, short-lived honeymoon periods are also common. Yes and no. Testosterone applied to the scrotum does efficiently convert to DHT. However, this does not apply to testosterone enanthate. The reason...

I've found it's not an easy issue to overcome if you're injecting in a location that's prone to such leakage. You can try injecting more slowly and/or withdrawing the needle more slowly afterwards. You can also try injecting smaller amounts more often. Otherwise try different injection...

Yes. You should know him. He has posted here as "RobRoy" and previously as "J. Keith Nichols MD". He has quite an ego, and a temper that flares whenever he is questioned.

Dr. Nichols and presumably some others in the TOT crowd. ChatGPT says "Some of his discussions of TRT, while emphasizing a holistic approach, have included mentions that, in specific cases, higher T doses may be needed to optimize the ratio of T to E."

Absorption via injection is almost 100%. And once the testosterone gets into circulation your body can't tell if it was injected or manufactured in the testicles. At that point the only differentiation is in the pharmacokinetics—basically the serum concentration and how it changes over time. If...

That's basically argument from authority. They may simply be responding to the demands of their customers, who by and large have more-is-better thinking. I see that @Willyt has already mentioned Xyosted. Its success dispels the notion that supra-physiological doses are needed to ameliorate...

The protocol is effective, but requires a lot of motivation to sustain. That's why I've expressed enthusiasm for short acting testosterone, such as nasal gels. With these there is continued production of those upstream hormones, along with less downstream disruption.

There's the usual quibble that 105 mg TC/week is nowhere near micro-dosing. In any case, I've hypothesized that a SERM is needed in addition to cistanche to improve the odds of significant LH production under TRT. Ostensibly cistanche attenuates negative feedback from androgens at the...

That's not quite how it works. A reference range is supposed to be established by sampling the healthy portion of the subject population. Now you can argue on an individual basis whether the criteria for being considered healthy are sufficiently rigorous. But don't make a blanket statement...

High estradiol, whether absolute or relative, is a concern because the long-term effects are not well studied. There are at least some hints that it is problematic. Elevated estradiol levels result in vacuolization and increased glycoprotein production impairing Sertoli cell function. It also...

I'll begin with my usual admonitions: contrary to popular perception, 80 mg/week of TE is not a low dose, physiologically speaking. That's over 8 mg/day of testosterone, while typical natural production for healthy young guys is 6-7 mg/day. In some cases injecting twice weekly can make a dose...

Regarding the emotional blunting, high and/or steady testosterone levels can mess with the adrenal axis, which in turn can yield the emotional effects. There can also be effects on dopamine and serotonin. Here's an interesting statement I found earlier. Because circulating T normally...

Even if such upregulation occurs, the effect is clearly swamped by the SERM. That is, at typical doses, concentrations of the SERMs are more than enough to antagonize some additional estrogen receptors.

It is actually heightened sensitivity to estradiol at the pituitary or hypothalamus that can produce secondary hypogonadism. The SERM dulls this sensitivity by antagonizing the receptors. That is, the feedback is negative, so when reduced it yields a positive effect, a significant increase in LH.

A reasonable starting protocol is 40 mg twice a week, or 25 mg three times a week. This is one area where I criticize Defy. It's ridiculous to start somebody on a protocol that provides more than double high-end natural production of testosterone. That is, the normal range of testosterone...

It does seem likely that you have underlying metabolic dysfunction. Throwing TRT at this may or may not be useful. So far it is not clearly established that you are hypogonadal. You need to determine free testosterone before reaching a conclusion on that front. The Vermeulen calculation puts...

This work finds that DSIP can cross the blood-brain barrier. But it may be that nasal administration bypasses regulation of how much can get through. In all cases, we found intact peptide entering the CNS in excess of vascular markers. This clearly demonstrated that the small peptide DSIP could...