Back in October I got my levels checked, and my doctor was pretty happy. E was 144 pg/mL, T was 42ng/dL. I was pretty happy with the effects I was seeing, and she said it looks good and we'll check again in a few months.

A few months have passed and so I went to get my blood test. Now E is "<50 pg/mL" and T is 448 ng/dL. Nothing has changed, except I've gotten pretty excellent breast growth (especially for a short amount of time, I'm solidly a 34B now) and fat redistribution (my hips are wider than my chest for the first time in my life).  I've seen a few other effects too; my band size went down as I (presumably) have less back muscle, and the hair on my upper legs has been growing much slower. My nipples are still quite sore even today and yesterday.

Overall I've been pretty happy - and effects were very noticeable. So what gives?

I wear patches and take spiro, which hasn't changed since my last test.

Even when I started at the same level of E but half the spiro, my T level was around 200 ng/dL.

So... what the heck? Is this a test error? Has this happened to anyone else?

One reason I got off of patches they were a mess with my levels. And they will probably edit ur post since you have stated ur dosages.



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Patches don't deliver a constant dosage. When you first slap one on, your levels will be higher than when it's time to apply another one. People wearing more than one patch often stagger them rather than apply both patches at the same time in order to level out the swings a bit more. Estrogen just doesn't last long in the body and about the only really constant delivery system is implants so knowing when your received your last dosage is important in interpreting your results. Possibly the best indicator is if your getting proper development. If you are, don't worry about your levels.

Quote from: Dena on February 06, 2018, 05:45:36 PM
Patches don't deliver a constant dosage. When you first slap one on, your levels will be higher than when it's time to apply another one. People wearing more than one patch often stagger them rather than apply both patches at the same time in order to level out the swings a bit more. Estrogen just doesn't last long in the body and about the only really constant delivery system is implants so knowing when your received your last dosage is important in interpreting your results. Possibly the best indicator is if your getting proper development. If you are, don't worry about your levels.

So, two things - First, I thought (with oral, which is known to be very spikey) we were supposed to worry about trough numbers, not peak?  In which case I got a very low trough number

Second, even if my E is not steady because of the patch, what's up with my T being so high? It's  more than 10x what it was in the previous measurement.

As for variation over the time the patch is applied - I looked at the prescribing information... It honestly seems to vary a lot with delivery system. There are graphs for these things that make it much more clear, but... mine is the Sandoz generic for Vivelle Dot, and Vivelle Dot has excellent maintenance of levels across the entire normal 84 hour time range. The minimum is (on average) 85 vs an average of 105 for the patch applied to the buttocks (which is what I do). Applied to the abdomen you get even "cleaner" numbers, the 84 hour min is actually slightly ABOVE the average (because the curve really is pretty flat)

(That' comes from the Vivelle Dot prescribing information (the sandoz is identical, from what I can tell, though I will check when I get the chance): <link removed by moderator>

Other delivery systems look worse; Climara is a steady decline - at the 168 hour point it's still way above baseline but has generally declined.  Minivelle looks terrible; it maintains its dose for 1.5 days and then tanks hard.

The increase in T sounds a bit strange.... Have you started or had changes to other medications during this time...herbals can be known impact some medications? Any physical changes? Bad LAB report? just a couple of suggestions...hope you can work it out.

Take care

Liz

Quote from: Dena on February 06, 2018, 05:45:36 PMPossibly the best indicator is if your getting proper development. If you are, don't worry about your levels.

Exactly that! +1

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Quote from: ElizabethK on February 06, 2018, 07:40:31 PM
The increase in T sounds a bit strange.... Have you started or had changes to other medications during this time...herbals can be known impact some medications? Any physical changes? Bad LAB report? just a couple of suggestions...hope you can work it out.

Take care

Liz

I don't think I've changed anything.  I never was much into herbal medicines.

Physical changes... I have way more breasts than I had before, and less muscle and so on.  I've gotten decent effects.  Though if those were tapering off I don't know how I'd know. My weight has been very steady the entire time.

Mentally... I've felt noticeably spacier than usual the last week or two. Less focus, less short term memory. I have ADHD and this isn't entirely out of the realm of normal for me, but it has been noticeable. Also more energy (especially physical energy) but I've been exercising more and drinking a little less so that's not entirely a surprise either.

Also when I started HRT, after about 3 weeks I got into this zen-like state of contentment with everything. Really low anxiety, really clear head. That lasted several weeks, but gradually went down, partially as a result of life events, that returned me to pretty normal (and annoyingly high) levels of anxiety a little after my last test.  Kind of miss that reduction in anxiety.

Two thoughts come to mind. Labs do make mistakes and if you think thats the case, you can go in for another test. The second possibility is your body adjusted to the dosage and your doctor may need to adjust for the change. This is the reason that a "Standard Dosage" really doesn't exist. Some of us work well with a book dosage while others require more or less. At this point you need to follow up with your doctor and see what your doctor thinks.

An update, since my doctor got back. I hopefully don't fall afoul of anything to say that she recommended an increase in Spiro and to hold off on more E2 until another test in about a month.  I'm a bit cranky and of course want tests sooner and so on, but I'll defer to the doctor.

As for why... With the understanding that this is 100% theory, and mostly unprovable theory at that:

After several days of obsessing and thinking, I think it's most likely that my case is driven by some amount of Androgen insensitivity. I could go into tons of details, but basically, I've never been that strongly virilized.. My voice was frequently described as annoyingly high (long before I identified as trans - I always tried to lower it), I have relatively little body hair, my beard hair growth was mediocre. Physical ability, my face, etc... not feminine per se but on the feminine side of the masculine range.

Also my baseline T was rather high.  Which, given feedback mechanisms, makes some sense.

When I got on HRT, I noticed effects very quickly, because even at a low Spiro dose, it was enough that E2 could shine through (and besides, aromatase could do its thing). Feedback being what it is my body responded by cranking up the T as best it could.  So my T rebounded, as measured.

E2 is trickier to explain. There's really no reason for that to be low other than if I got a bad patch or a bad reading. Even with high T, I'd assume endogenous E2 would be high because Aromatase has more to work with. Sadly I don't have a baseline or anything to work with other than the 1 "good" measurement and the more recent "bad" one.

There are really more questions than answers down this rabbit hole, when I start looking at things like DHT, aromatase, etc. But it does create a path where it's plausible for me to get feminization with still having fairly high T numbers... especially with Spiro being an AR antagonist anyway.

From what I've been reading about Spiro, it seems it's much more an androgen blocker than a reducer (through increased metabolic clearance and interference with cytochrome P-450 in testicular and adrenal tissue) so if T doesn't go down, it's really not surprising given men on high doses for several months saw no change in T but still experienced gynecomastia and semen abnormalities. The E would reduce the T and if E is low, high T.

E is really one of those hormones that fluctuates a lot, even on patches so I find that it's hard to rely on blood tests for that. But, Spiro seems to increase conversion of androgen to estrogen so higher estrone and estradiol.

In the end, I find what matters for me the most is the end results, as in breast growth, overall feminization, and feeling good. I think sometimes, those numbers we see distract us from what is really important. Just my 2 cents.

QuoteFrom what I've been reading about Spiro, it seems it's much more an androgen blocker than a reducer

It does block a bunch of the enzymes involved in synthesis of androgen, so it is at least a partial reducer.  Of course, less T synthesis also means less E synthesis because Aromatase etc.  Also obnoxiously it achieves a lot (perhaps even most) of its affects through its metabolites, so it gets really hard to understand.  It screws with like half of the enzymes in this chart: https://en.wikipedia.org/wiki/Testosterone#/media/File:Steroidogenesis.svg

When I started hormones I asked my doctor - "wait, if the goal is to have natal female T and E levels... but the path to that is an Android Receptor Blocker... wouldn't that mean less AR activation than what a cis woman would have?"  And her response felt like "Well.... there's a lot we don't know and but usually that works out"

So it is, being trans... there's a big gap between complicated stuff like gene expression, receptors, enzymes... and observed effects. The only way to bridge that gap is with well controlled studies, which don't exist nearly as much as I wish they did.

Quote from: JennyJupiter on February 12, 2018, 03:35:22 PM
It does block a bunch of the enzymes involved in synthesis of androgen

In-vitro, in rats. My personal feeling, based on my own readings, is that it doesn't have such a great impact on T levels and that probably, the estrogen is mostly responsible for T reduction.

Quote from: KayXo on February 14, 2018, 06:11:44 AM
In-vitro, in rats. My personal feeling, based on my own readings, is that it doesn't have such a great impact on T levels and that probably, the estrogen is mostly responsible for T reduction.

Spiro is such a complicated, all over the place kind of drug... I don't really understand why it's the preferred one in the US.  It affects all kinds of receptors including ones that have nothing to do with the sex steroids, like glucocorticoids.  And of course there's the fact that so much of its action is accomplished by its metabolites which are only partially studied.  It's just SO COMPLICATED.  It's affecting all kinds of random and unrelated things.

And yes, one of my ever growing concerns with my doctor is that her preference is to crank up spiro to get T down (which doesn't seem super effective anyway) and be very hesitant to increase E. I don't understand why.  We know very high levels of E can be physiological and tolerated (in pregnancy). 

Even from a very abstract viewpoint I reject it; I want feminization far more than de-masculinization. Why not get E levels to where you want them and then get T down?  Her approach is reasonably mainstream I just don't understand why it is so. I don't want the side effects of having no testosterone or AR activation.

I think it's the spectre of VTE caused by EE that's at work here, much as it is when it comes to surgery. That, and that spironolactone can so often induce gynecomastia on its own. Spiro is viewed as safe and hey! It causes boobs often! (Which I think the trans-feminine community is a bit obsessed with when it comes to HRT impacts).  Meanwhile E2 is "dangerous" because of VTE, so why not just throw spiro at the problem?

On the bright side, if it's primarily a receptor-blocker and not a synthesis one, I still get more downstream E2 because of aromatase.  Which is maybe a good thing overall, because so much E2 (like DHT) is synthesized in target tissues.

I like you Jenny, I mean...how you think. 

Finally met with my doctor in person today and now she suggested increasing the estradiol before I could even kick up a fuss about it. She actually forgot she told me to increase the spiro before.

Her words were "it's inaccurate... but at least we want detectable levels".  What a forehead slapper.

She says, overall, that this isn't too unusual, for the body to produce more T (and somehow less E) after getting good values earlier.