Thread by @mspowahs

A thread on blood testing for transfeminine HRT, beyond just checking estrogen and testosterone levels, heavily based on my recent personal experiences attempting to validate some long-standing hunches about my medical transition.

I'm not a doctor, and this isn't medical advice. It's every individual's right to decide their own best path for accessing the outcomes they desire, and obligation to do so responsibly. If you have corrections, clarifications, or contradicting info, please feel free to share.

This info is shared in the spirit of acknowledgement that many of us are in the position of managing our own treatment, even when under a physician's care. I do think the best outcomes come from informed doctors AND patients working together.

Me: 36yo, HRT since 30yo.
DIY (1y) ➞ Prescription (5y). Orchi 2018.

Stopped HRT 9 months in, resumed 5 months later.
Experimented with various HRT doses earlier in transition.
Long-term effect on endocrine system unclear.

Current HRT: 1mL estradiol cypionate (5mg) every week.

For the past few years, I've felt "stalled" in my transition. The likely answer was sour grapes at my own genetics, but I haven't been able to shake the feeling that something else was up. Both higher AND lower E doses seem to work for a bit, then changes peter out. Ditto with P.

Most doctors only order labs for the total estrogen and testosterone in your body. My levels always come back fine: T pretty low, E where you're supposed to want it, both well within reference ranges.

Cycling hormones kinda helped, but the trough of my cycles felt extremely low, and the peaks just felt like what I expected standard HRT to feel like. I wasn't satisfied.

I finally found a progressive provider willing to order a bunch of labs, checking for the following things:

(Blood was drawn at the end of a 7-day cycle, so theoretically these are all the lowest levels I have.)

Total E2 (estradiol). Main feminizing hormone. Standard in blood tests.

Ref: ~150–500pg/mL.
Mine: 392pg/mL.

Interpretation: Good, but higher than expected at end of cycle.

Free E2 (estradiol). How much of your total E2 isn't bound to anything else, providing a more accurate measure of E2 concentration than total estradiol alone.

Target: >1%–2%
Mine: ~1.5% (5.92pg/mL)

Interpretation: Okay, but curious considering high total E2. Could be higher.

E1S (estrone sulfate). An estrogen precursor. Not the same as E1 (estrone). Circulating E1S acts as a "reservoir" for E2 synthesis, especially in peripheral tissues (like breasts).

Ref: ~200–5000pg/mL (doc targets >6000pg/mL)
Mine: 2460pg/mL

Interpretation: Could be higher.

Total testosterone. Main masculinizing hormone. Standard in blood tests.

Ref: 2–24ng/dL
Mine: 19ng/dL

Interpretation: Reasonably low, but possibly higher than expected for someone who no longer has gonads and is effectively on estrogen monotherapy.

SHBG (Sex Hormone Binding Globulin). A reactive scavenger of excess hormones; responds to high levels of E *and* T and lowers them. Preferential binding to testosterone.

Ref: 17–124nmol/L
Mine: 171 (!)

Interpretation: HERE we go. Curious Thing #1. My E2 dose might be too high?

DHT (dihydrotestosterone). A metabolite of testosterone with its own potent masculinizing effects.

Ref: <20ng/dL (my doc targets <10ng/dL)
Mine: 16ng/dL

Interpretation: Curious Thing #2! A little higher than expected and preferred. Could be counteracting some feminization.

3α-Androstanediol. A DHT metabolite, and possibly an indicator of other circulating androgens/androgen production from other sources (adrenals, kidneys).

Ref: 38–576ng/dL
Mine: 479ng/dL

Interpretation: CT#3. Higher than doc prefers—and again, I got no nads. Something IS up.

Putting it all together: My total E2 and T look fine, but my DHT, SHBG, and 3α suggest that something's not ideal with my endocrinology. SHBG might be lowering my free E2, yet I still have non-preferred levels of androgens that it should be proportionally lowering more.

I didn't order a free T test, which could tell me how much of that 19ng/dL is actually "in use". But, to the best of my understanding, since 3α is a metabolite, my 3α levels are a reasonably accurate indication of androgen activity *besides* whatever's being bound to SHBG.

This possibly explains my cycling and paradoxical dosing experiences.

High E2 dose: initial increase in available E2, then a reduction in free E2 once SHBG catches up.

Low E2 dose: possible increase in free E2 from SHBG backing off, but feminization impacted by other androgens.

Based on these labs, my provider and I are making the following changes to my HRT:
- Bicalutimide, which blocks androgenic action at the receptor level—meaning circulating amounts don't get to do their thing.
- Lowering E2 dose slightly, 0.8mL (4mg) a week, to invite less SHBG.

I'm also going back on a small dose of oral (not sublingual) estradiol pills, in addition to injections, to replenish E1S and intentionally invite estrone metabolization in the liver, which might promote further breast development.

(It might raise SHBG; will keep an eye on it).

In collaboration with my provider, I'm also trying these more experimental, but anecdotally promising changes:
- Supplementing with boron, a non-hormonal mineral which binds to SHBG.
- Going back to microdosing T, which should also lower SHBG while being blocked by bicalutimide.

And finally, I'm making an appointment to get implantable estrogen pellets, which show great promise at an increase in free E2 levels with very low SHBG response.

For final reference, here are the blood tests I ordered that don't normally get ordered, but provided additional diagnostic context:
- Free E2
- SHBG
- DHT
- 3α-Androstanediol glucoronide
- Estrone sulfate (E1S)

And since some will ask and others will guess, yes, I'm working with an NP at the practice of Dr. Will Powers (no relation). I don't agree with all his thoughts, behavior, or conclusions, and I'm not a "Powers Method" superfan, but I appreciate his thorough diagnostic approach.

Thanks for letting me indulgently braindump about my medical treatment—I hope it was at least somewhat informative. My main takeaway is that while we do the work of accepting the limitations of our medical transition, we can also work to make sure we're not accidentally settling.

I'll eventually update this thread with info about how these hypotheses/treatments are borne out in practice.

If you have anything to contribute, please let me know, and if anyone wants a deeper/broader dive on any of these topics, I can give it my best shot.

Thanks!