Fatigue, anger, swollen ankles, etc.

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I'm currently dealing with a few things that may or may not be TRT related. I scoured these forums to see if I could find help with no conclusive answers.

Background:
  • 38, 5'11", 205lbs
  • TRT since Feb 2018, currently 138mg/week (3x) + 500IU HCG (2x) + .125mg Anastrozole 2-3x as needed
  • DHEA 25mg / Pregnenolone 10mg nightly
  • Powerlifting for the past 2 years 3x/week otherwise sedentary
  • Diet could be better but not terrible, on the higher carb range
Labs (Feb 2019, LabCorp ranges):
  • TT: 723 / FT: 25.4
  • E2: 36.6
  • Hematocrit: 49.3
  • Cholesterol a bit high, otherwise all tests normal
I've been feeling fatigued and out of breath easily for a few months now. I should be in better shape with my regular workout schedule. A couple weeks ago I started getting swollen ankles. Not horrible, not painful, but visibly swollen which is worrisome. Prone to anger too. Lashed out at a good friend recently which was very out of character.

This seems to point to E2, but the labs are fine and almost a year ago the numbers were similar and I felt much better. I had issues when it climbed to the 60s, but the mid-30s were fine until recently.

Any ideas or leads?

All GPs I've seen from Kaiser are VERY anti-TRT so every time I come to them with a complaint they tell me to stop it and go on statins cause my cholesterol is a bit high. I don't want to deal with them for any chronic issues anymore.
 
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I'm curious, did you ever resolve these symptoms? It sounds like you were diagnosed with sleep apena, which could explain the fatigue. Did the ankle swelling subside?
 
Fatigue/feeling out of breath subsided after a phlebotomy.

Anger/volatile emotions subsided by going back on a daily regimen and reducing my overall weekly dosage to 119mg.

Ankle swelling still present...
 
It's great to hear you were able to resolve some of those issues.

I used the "free E2 calculator" spreadsheet to calculate an approximate "free E2" for you, which was 1.11 pg/mL. Range in men is supposedly 0.2 - 1.5 (Free Estradiol (Sensitive)). But this calculator /may/ be more accurate using the "standard" E2 test values versus the sensitive, interestingly enough. So if you have a standard E2 reading it may be worth sharing. If you standard E2 is significantly higher and that's a true trough reading of E2, you could maybe be trending into too-high E2 territory, leading to the water retention.

Another possibility, without any evidence right now -- and just throwing this out there in case you're looking for paths to tread down to investigate -- is that maybe your progesterone is low relative to your estrogen: Could the ratio of progesterone to estradiol affect water retention? I'm looking more into this myself soon, and -- again -- there's no evidence as of now that this could be a factor, but I'm just throwing it out there as it could explain water retention with normal E2. Some men have low progesterone even with HCG.

Yet another possibility is that HCG itself[1] could be causing the water retention. So you could try removing HCG and seeing if it resolves. Of course, it could be due to extra T/E2 from the HCG, so you may want to try this option last.

1. I'm not sure of the mechanism, but I've read a lot of reports of guys having water retention via HCG with normal E2. One possibility is the metabolite of pregnenolone, androstenediol, which binds to the estrogen receptors but is itself not E2. I'm digging into this as well..
 
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It's great to hear you were able to resolve some of those issues.

I used the "free E2 calculator" spreadsheet to calculate an approximate "free E2" for you, which was 1.11 pg/mL. Range in men is supposedly 0.2 - 1.5 (Free Estradiol (Sensitive)). But this calculator /may/ be more accurate using the "standard" E2 test values versus the sensitive, interestingly enough. So if you have a standard E2 reading it may be worth sharing. If you standard E2 is significantly higher and that's a true trough reading of E2, you could maybe be trending into too-high E2 territory, leading to the water retention.

Another possibility, without any evidence right now -- and just throwing this out there in case you're looking for paths to tread down to investigate -- is that maybe your progesterone is low relative to your estrogen: Could the ratio of progesterone to estradiol affect water retention? I'm looking more into this myself soon, and -- again -- there's no evidence as of now that this could be a factor, but I'm just throwing it out there as it could explain water retention with normal E2. Some men have low progesterone even with HCG.

Yet another possibility is that HCG itself[1] could be causing the water retention. So you could try removing HCG and seeing if it resolves. Of course, it could be due to extra T/E2 from the HCG, so you may want to try this option last.

1. I'm not sure of the mechanism, but I've read a lot of reports of guys having water retention via HCG with normal E2. One possibility is the metabolite of pregnenolone, androstenediol, which binds to the estrogen receptors but is itself not E2. I'm digging into this as well..

Wow thank you for taking the time to respond and share what you've found out so far. I really appreciate it.

I'm not too worried about the water retention quite yet, it comes and goes and it's mild. What made me consider it was the possibility it was related to the other symptoms and it could indicate something more serious.

The phlebotomy made a gigantic difference. I'm getting new labs soon and I'm curious to see what my current numbers are, specially HCT and FT. I do feel good and stable currently, specially if I can get good sleep (rare), but the lower T dose also means less energy and lesser performance at the gym...

Incidentally, I never felt my recovery improved much on TRT. I think it's just my chronic sleep deprivation, but I was hoping for a boost from the treatment, but in 1.5yrs on it, I still can't handle more than 3 training days without feeling extremely beat up.
 
'm not too worried about the water retention quite yet, it comes and goes and it's mild.

Coming off TRT two months ago I was in my third week of stopping, I was prescribe a pill for edema and 4 hours after taking it I had good erections, mental clarity, lots of energy and felt normal.

I didn't really have visible swelling either, but I had trouble keeping potassium up (even while supplementing) which these medications can deplete.
 
DHEA makes me feel horible after taking it for 2 weeks.
Tried taking it twice and had same result each time, 25mg.
-Anxious, tired, irrational thoughts
I suggest getting off of the DHEA for a couple weeks and see how you feel.
 
Coming off TRT two months ago I was in my third week of stopping, I was prescribe a pill for edema and 4 hours after taking it I had good erections, mental clarity, lots of energy and felt normal.

I didn't really have visible swelling either, but I had trouble keeping potassium up (even while supplementing) which these medications can deplete.

Which medication was this?
 
It was hydrochlorothiazide and as with everything else I over respond to it. I only needed an 1/8th of a tablet.

how long did you take it? I have some on hand and felt pretty darn good when I took it. Discontinued because it seemed to throw off my blood sugar (which recovered when I stopped) but I did sleep better and feel good on it.
 
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This points to poor diet. It blows my mind how TRT users dont clean up their bad habits once they start treatment. Eat better and swelling will resolve itself. Eat better and you will sleep better. How often do you have sex? The more I get the more relaxed I am throughout the week. Lashing out can be out of character but youre also in flux and you begin to have less patience for crap. You caught yourself so time to add a little meditation and less salt to your day.
 
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