Hi!

tl;dr after injecting the same amount of estradiol valerate (subq) for a month or so, I started to experience more dysphoria and signs of testosterone (esp. mental) started to come back. Any reason this might be?

Longer version / details:

I injected 5 mg (0.25 mL) of estradiol valerate subq into my thighs every four days for a while, and for a couple weeks I started injecting into my abdomen instead to avoid blood supplies.

This dose seemed like more than enough. In the past 3.4 mg every 3 days gave me blood estradiol levels of ~350 pg/mL at trough. Recent labs showed 5 mg every 4 days had ~300 pg/mL at trough for me, which was lower than I expected.

It’s a good level, but I was having weird dysphoric experiences that commonly happen when my hormones are out of wack (usually when I’m taking too little estrogen). Things like really doubting my gender identity, depression (lack of motivation, lethargic), anhedonia (little pleasure, flat affect, often leads to craving short-term reward behaviors). Physiological signs of T were not as evident in this case, and the dysphoria was not as severe as in the past when my estrogen was too low. Still, it seemed a lot like my estrogen was too low.

I increased my dose to 5.4 mg and the dysphoria went away within a day and I felt amazing and continued to feel amazing. I intended to switch to 5.4 mg / 4 days instead, but on day 3 I could feel my hormones coming down and trusting my experience I injected 5 mg a day early with the intention of trying 5 mg / 3 days (which is a lot more than I have taken before in terms of what this should do to my overall levels). Still not sure what I will do next. Part of me wants to stick with a 4 day cycle to keep lower peaks and to minimize overall levels (out of principle, I know injecting is not as risky as oral routes).

I’m trying to figure out why a stable dose that seems so high and was for the most part effective would suddenly not be “enough” (assuming that’s indeed what’s happening).

For context I’m close to 4 months on HRT, I took bicalutamide for a bit but stopped because I don’t think it helped my mental symptoms and that’s the most important therapeutic goal for me with taking HRT. I switched to monotherapy after 2 months which is when I started the 5 mg / 4 days.

I’ve heard sometimes the body can go through phases as it adjusts to estrogen early in HRT, so maybe this is just one of those lurches or adjustments?

Anyway here are some guesses I came up with:

  • I gained some weight (like 15 lbs), some maybe I need a little more EV than before?
  • injecting into abdomen depots the oil differently than the thigh, so maybe I am seeing a slower or lower circulation of EV (or alternatively a much faster circulation that is causing a crash earlier?)
  • maybe the estrogen receptors are downregulating due to taking too high of a dose too regularly? (I see lots of debate about whether this is a thing, mostly people on Reddit rejecting the idea that this has any clinical relevance.)

Just wondering if anyone else has experienced this or has suggestions.

Thanks so much!

  • There have been some times where I was sure my E is low and T high, but when I got the blood test the levels were fine. Dysphoria can really distort your perception. Because you’re already at the higher end of ev doses, My advice is to not increase or shorten the cycle until you get another lab suggesting you need to.

      • Yeah, I felt the same way (much better after an injection, even though the labs showed my levels were probably fine at time of injection). My theory is that I got used to very high, pregnancy-levels of E. Then when my levels went back down to the therapeutic range, it felt “off”. Just a theory, though!

        • Yeah, that was one of my hypotheses - that sustaining too high of a dose causes downregulation of the estrogen receptor, or something along those lines. A bit like a drug tolerance. That said, it’s unclear to me whether that kind of thing is actually likely or possible; I can only say it’s what the experience is like.

    • I started injecting into tummy around mid March, so I guess it’s been a month since I gave up on injecting into the thighs. I started the 5 mg / 4 days in mid February, so I guess it’s been two months at that dose.

      In that case it seems like injecting into the tummy shouldn’t be the reason I started to experience dysphoria. I do think sometimes that some injections depot better than others, and that it depends on various factors like whether I hit any blood supply, how much bleeding I cause when I inject, etc.

      Thanks for the tip on the thigh - I can’t remember if I’ve heard that as well, but it’s good to hear what people are experiencing.

      ❤️