FT, TT: How Much is Too Much?

My original post from last year: TRT Questions - Testosterone Replacement - Forums - T Nation

Quick summary: How far should I push my doctor to normalize my FT levels instead of my TT levels? Is it reasonable to expect out-of-reference-high TT from TRT to get my FT up?

Background: 27 year-old with idiopathic pituitary-originating hypogonadism, on TRT for a little over three months now.

My current dose of IM test cyp is 125mg/w, distributed as 80mg e5d.

My SHBG is quite high (10/22: 55.9 nmol/L on a 16.5-55.9 reference) and my bioavailability is quite low (10/22, %Free/Weakly-bound 6.7% on 9.0%-46.0% reference). Body composition and e2 are quite normal; it’s just SHBG that appears to be stratospheric.

The binding issues render my free T disproportionately low relative to my total T; the 10/22 testing (pre-treatment) had me at 301 TT (348-1197 ref) but only 20.2 F/W-bound (40.0-250.0 ref). A test before that was 170 TT with 1.6 FT on a 9.3-26.5 range.

The last trough test before upping my dose from 100->125mg per week had me at 414 TT, which would correlate to 27.8 F/W-bound if ratios remained constant–still very low and very below reference range.

Assuming the 25% increase brings me up 25% or so, together with the frequency increase I expect my next trough check in mid-March to come back around 600 TT; best-case scenario, I’d expect this to bring my estimated F/W-bound to the very low end of the reference range, and my “peak” wouldn’t be much higher than this.

Subjectively, I’ve noted definite improvements since treatment initiation, but I’m nowhere near where I want to be.

Assuming a linear relationship, though (I know this isn’t the case, but bear with me), achieving a mid-reference F/W-bound (145 on 40-250) would require a TT of over 2000 ng/dL, nearly double the reference range and likely triple my current TRT dose. I have a hard time believing I’m going to talk my endo (or most any doctor) into anything even approaching this dramatic–it’s hard to think of 300mg+ per week as a TRT dose and not an AAS dose.

Is pursuing a higher and higher dosage until my FT (or F/W-bound, bioavailable, what have you) and subjective metrics improve the right way to go? I wish I could just raise my bioavailability, but from what I’ve read, that’s not really something you can directly alter. I’m starting to feel a little disheartened, because it seems like I finally found the right road, only to have my car break down on mile 3.

What do you guys think? Anyone run into similar issues?

Keep in mind that free T is a calculation using total T and SHBG in a simple equation. Equations don’t take everything into account, and any discrepancy in numbers gives you a flawed result. Your albumin and possibly other proteins with any affinity for T can also affect free T. I’m not saying it isn’t possibly the source of trouble but remaining open to the interpretation of labs is vital in medicine. Numbers are not everything. Certainly not one or two sets of them. They are just helpful indicators. For example you may have an immunoglobulin that has an affinity for the immunoessay that tests for SHBG and give a false high number(just a hypothesis).

The calculation for estimated glomerular filtration is a good example of a flawed method. The equation does not take into account muscle mass. Anyone with two to three times the normal percentage of muscle is going to appear to be in one of the stages of renal failure due to the elevated creatinine entered into the formula.

Thanks, C27. Yes, I totally understand that the calculations are dubious, and trying to precisely calculate treatment based on those limited-input calculations is not the right way to go. Pretty much everything else in my CBC/CMP tests came back normal, so there’s less that I think could be messing with it, but there’s still undoubted variability.

At the same time, I know for sure that my treatment right now isn’t working. It’s produced an improvement, but it’s intermittent and feels incomplete. Hopefully, continuing to discuss this with my doctor and doing gradual dose increases will end up addressing everything, but the numbers that I do have concern me in their potential to create a gulf that nobody’s going to cross. Maybe it’s just premature worrying combined with impatience.

I know it’s frustrating at times. Seems like docs know nothing and new evidence based research isn’t exactly flooding in on the subject. Be patient. Like you said there have been some improvements. Sometimes the direction of dose is contrary to initial impressions. You’re already fairly high dosed at 125mg/week. I’m on 50mg/week and get good muscle gains and back acne due to increased androgens. Increasing the dose will not create a linear correlation of total T or free T. There’s more to the intravascular and intracellular management of substances than is readily apparent.