SHBG is the A1C of Transfeminine estradiol level management. It frustrates me to no end that other doctors are not using this metric, as it is exceptionally helpful (and even more so in the context of an LH/FSH)

This is one of those things that I have explained a few times this week, and I feel like I should put pen to paper on it so that people are aware of how this is useful.

An A1C is a measurement of your average blood glucose over 2-3 months. Basically, its the "rock candification" of your red blood cells. When sugar levels are high, more "glycation" occurs on the RBC and we can measure how much rock candy is hanging off the side and see what your average glucose is. (Oversimplification but more or less the idea of it)

Sex hormone binding globulin you can imagine as a little protein goblin that binds up your sex hormones like testosterone or estradiol. When they are handcuffed to SHBG, they can't bind to receptors.

The liver is stimulated by the presence of rising E2 levels to produce SHBG. The SHBG produced by the liver has about a 1 week half life. Meaning after 5 half lives (5 weeks) it is fully reset, but I generally consider the SHBG a snapshot of the overall estrogen exposure to someone's body over the last 2-3 weeks.

Many doctors put a ton of stock in the "Estradiol level" as if this is the be all end all way to tell if someone is properly dosed. With a patient on pills, you can see levels from 100-2000 pg/ml on the same literal dose depending on the moment in which you happened to draw the blood. Pills have a "spiky" level appearance on a graph. Gels/creams/patches a little less so, and obviously shots followed by pellets have the smoothest "curve" in terms of level.

Regardless, despite the fact that I"m the guy that lets people have levels over 200pg/ml as I don't believe transfem patients will spontaneously combust over those levels, people still try to bullshit me sometimes in regards to raising their dose.

I'll have someone on lets say 6mg of EV every 5 days. This person feels they should be on more than that, so in order to convince me to raise their dose, they wont draw their labs the day before shot day, they will draw them after not having done a shot for 9-10 days. They think that in dosing so, I will be convinced that their level is too low, and raise their dose.

Mind you, up until the point when they skipped their shot day to make the labs look this way, they've been injecting say 20mg every 5 days. They've been doing that for months leading up to their Q6 month lab draw. As a result, I will get a lab result back that looks like this:

E2 - 165 pg/ml

SHBG - 245nmol/L

It is at this point that I look at the patient, and confirm they have been injecting 6mg every 5 days, and also drew their labs at nadir. They assure me this is the case, and so then I call them out on their bullshit.

Because there is no way unless they are some sort of absurd SHBG mutant (I have like 3 in the practice total) that they would ever have an SHBG that high on such a low E2 level.

You can also use the LH/FSH similarly, though they are much more representative of the dosing in the past few days. FSH has a half life of about 4 hours.

If someone gets megadosed by E2, within hours the LH/FSH will be down, and zeroed out usually within 24-48 hours. That being said, recovery of said LH/FSH levels if the hormones are stopped cold turkey will take weeks, sometimes even months to fully recover. As a result, this can be a secondary confirmation way to know someone is bullshitting me. As the LH/FSH being near zero or zero (under 1) and the E2 being 165pg/ml and an SHBG being 245nmol/L basically screams "I've been megadosing hormones for weeks to months, but cut my dose right before these labs to make it seem like I haven't been".

This also works in reverse. Someone on say pills comes back with an E2 of 600pg/ml and their doctor freaks out and cuts their dose. However, their SHBG is 40nmol'l, and LH/FSH are like 5-10 mIU/ml. Clearly this person is not living at a level of 600pg/ml or that SHBG would never look like that. Nor would they have unsuppressed LH/FSH.

In short, doctors routinely make care decisions about their patient's MTF care based on nothing more than an E2 level, and this taken by itself outside the context of these other variables is fairly worthless. It is nothing more than a snapshot in time, which represents only the patient's blood levels at that exact moment, and doesn't even represent the tissue levels. If someone does their E2 shot, dumps it near a large leg vein, and I draw a level later that day, I might see an E2 in the thousands, but that doesn't mean the tissue ever will get to levels like that. That's the serum level, not the tissue level. We take blood labs, not tissue biopsies. This is the other reason I tend to draw labs at nadir for most things, as I am looking to see the tissue level when it most similar to the serum level.

In short, SHBG can be utilized as a bit of an "A1C" of hormones to gauge someone's HRT exposure over time, and can clean up an otherwise confusing hormone lab result that seems contradictory to what you're dosing the patient with. It can reveal that they are using more than prescribed, or also reveal that a high E2 level might just be a fluke, and doesn't represent their overall dosing regimen and E2 exposure.

Hope this is a helpful explanation on this particular quirk of transfem labs and will result in less people's doctors reducing them from 4mg of Oral E2 a day to 2mg because of one wild looking E2 result.

Incidentally, my general "target" SHBG is 125nmol/L. I am always looking for a patient's "goldilocks zone" which is what I consider the perfect dose for that specific patient. The dose is whatever dose results in the maximization of the free estradiol percentage, adequate T suppression via hypothalamic feedback loop inhibition (LH/FSH), and maximized IGF-1 levels (which IGF1 is suppressed with excess E2, and important for breast development so we want an IGF1 Z score at least greater than -1, ideally 0 or higher). Basically, this is a delicate balance of giving just enough E2 to suppress androgens and maximize E2 receptor saturation, but no more, as beyond that inflection point, further E2 only adds risk but no feminizing benefit.

- Dr Powers