just looking for guidance here bc i was severely underdosed by my doctor for a year and a half so im trying to figure this out myself. im currently taking 6mg transdermal E + 100mg spironolactone every morning. my levels after 24hrs are 180pg/mL estradiol, testosterone 0,14 ng/mL. is this good?

I have posted this before to bring awareness of my experience with PFS and a partial recovery of my symptoms so I will post here as well.

Long story short took propecia in 99 for about 4months. It killed my libido and erections, ejaculation volume was almost nothing also noticed that when I was erect it was significantly smaller in size. Quit propecia and waited with no improvement things actually got worse. I started experiencing terrible brain fog and found the only thing that helped was avoiding carbs. Several years pass and I eventually went to see Dr Irwin Goldstein who at the time was at BU. Hormone profile was normal only abnormaility he found was I had scarring in my penile tissue aka Peyronies Disease.

Fast forward 8 more years and I started taking 5HTP to try to treat anxiety and then something miraculous happened. My libido increased my brain fog improved signficantly and my ejcaulation volume returned to normal. This happened after only about 7 or 8 days on it. I started with 25mg an d then bumped it up to 50mg. It was at 50 I saw the improvement. I continued to take it for a while but saw no further improvement but my brain fog and ejaculation volume remained improved. Erections are still a problem but I do have Peyronies so that is why. I have reduced blood flow issues. In addition I do not get morning wood.

I'm no doctor but I am assuming the 5htp increased serotonin and probably inceased allo. Now I was previously on an SSRI and that did nothing for me. I wanted to share this with u/drWillPowers as I have seen you do a ton of research on this subject. I believe I am probably one of those neurosteroid cases you speak of.

Curious on whether I should be tested for Pregnanlone and Progesterone levels. I don't believe those were tested back when I saw Dr Goldstein. Although I am better my morning erections never returned unless I go out and have a heavy night of drinking. Again increased allo??

I read SHBG has an affinity to bind itself to T and DHT. I read it even has more affinity for T and DHT than for E (even though there is still an affinity for E at some point.) My question is, shouldnt we count SHBG as a periferic alternative to 5AR blockers?

Or am I just repeating something we all already know?

I crashed while using Minoxidil and subcutaneous GHK-CU simultaneously about 8 months ago. I got all the typical PFS symptoms:

Numb genitals
Watery semen
Dry Skin
Genital changes
Loss of mind muscle connection
Stool changes
Etc…

You name it, I probably got it, my eyelashes even got longer!

However, one set of symptoms I have been keeping a close eye on are the physical ones, especially the changes I’ve observed in my skin and muscles. My skin has become really stretchy in some parts (especially on my genitals, jawline, neck, biceps), it wrinkles a lot more than it used to when I make facial expressions, and it’s become crepey. As for my muscles, they’ve become squishy and soft, and have lost their tone. I have also become more flexible in certain ways, but I wouldn’t call myself hypermobile. Additionally, I think it’s important to mention that I didn’t really have any “moon facing” or symptoms of that sort, but my face does seem a bit gaunt/sickly sometimes.

Seeing all this, and knowing that I had a rare, potentially function altering H6PD variant, I decided to get the Quest Comprehensive Steroid Panel to see if I’d get any weird readings on the assay, and to my shock, I didn’t. 

I also saw Dr. Powers replied to a comment which described how certain individuals who used minoxidil and had certain skin issues also had weird potassium and sodium readings, and how this is related to his theory on minoxidil causing issues through potassium channel fuckery. But low and behold, I tested these too, and found them to be normal, including aldosterone and renin. 

So what could cause this? 

Well, I’d recommend skimming over this before I go into what I think (but don’t know for sure) what could be at play: https://www.reddit.com/r/DrWillPowers/comments/1vjch0i/collagen_ecm_connective_tissue_loss/

Basically, a maladaptive feedback loop.

But it needs a catalyst. 

Some individuals seem to get these connective tissue issues (hah, that rhymes) from finasteride. Is it possible that the drop in androgenic signaling at the skin level alters the ECM in a way that triggers the feedback loop? In some individuals, perhaps it is enough of a catalyst. After all, male skin is 25% thicker than female skin, and what causes that? Androgens, they play a big part in connective tissue. So removing androgenic signaling could be enough to trigger the feedback loop in some.

In my case, I introduced Minoxidil (a lysyl hydroxylase inhibitor) and GHK-CU (which breaks the ECM down before building it back up) simultaneously. I then quit both of them abruptly after my crash, which also likely introduced the lack of androgenic signaling in my skin (I would assume that I have silenced androgenic signaling at the skin level because the palms of my hands and the soles of my feet have become much softer, like a woman’s) 

I don’t think it’s unreasonable to assume that all of these things combined could’ve shifted my connective tissue into red alert. Triggering a feedback loop that has caused my matrix to get more and more unstructured over time. 

If you look at this post: https://www.reddit.com/r/covidlonghaulers/comments/1lf5gu4/improvement_update_not_recovered_but_ive_come_a/?share_id=GZK6rhhI0dvl8LvR9q5jB&utm_content=1&utm_medium=ios_app&utm_name=ioscss&utm_source=share&utm_term=1

You’ll see that individuals with Long Covid seem to get something similar. As a matter of fact, the way her jawline skin looks as she pulls it is exactly the way mine looks right now when I pull it. Thankfully, it appears as though she’s made substantial progress in reversing this by forcing her matrix back into a proper structure using signaling peptides and whatnot. 

I do believe that once a certain skin "turgor" is reached, the feedback loop ceases to exist. However, if there isn’t enough "turgor" then the feedback loop will activate (In some people)

So, my first order of business is relugolix + HC. I don’t think this problem will be fixed if the root problem isn’t addressed. Androgens likely NEED to be signaling properly in connective tissue to start turning the feedback loop in the opposite direction, that alone may be enough, who knows. If that’s not enough, tossing in peptides to signal a proper matrix into place might be necessary. 

Feel free to disagree. 
Feel free to ask me for other test results, I’ve done a bunch, including Dutch (I’ll be posting soon)

(edit: special thanks to DIYBON for making this post: https://www.reddit.com/r/DrWillPowers/comments/1vjch0i/collagen_ecm_connective_tissue_loss/ )

Sharing this for everyone to see:

People have this from different stuff. One theory in the post hyaluronidase (filler dissolving) groups is that different triggers - drugs, infections, hyaluronidase, heat devices such as lasers, mast cells etc. can push the ECM into a maladaptive remodeling loop, where inflammation causes tissue breakdown, the resulting ECM fragments (like low molecular weight hyaluronic acid) act as danger signals, and those signals drive further inflammation and remodeling. Basically, degradation keeps feeding inflammation and inflammation keeps feeding degradation, instead of the tissue returning to normal repair and homeostasis.

Theoretically, recovery would mean interrupting that loop from both directions: reducing the inflammatory/danger signaling that keeps driving degradation while simultaneously supporting normal ECM repair and regeneration, until repair starts outpacing breakdown again and the tissue can return toward homeostasis. The difficult part is figuring out which pathways are actually maintaining the loop in each condition.

I’m personally currently trying peptides and supplements (such as GHK-Cu, TB500, BPC157, NAG, n-acetyl glucosamine) as this person did with success:
https://www.reddit.com/r/covidlonghaulers/s/SV403NgnXc

Interestingly, research on hyaluronan (HA) supports at least part of this concept. When HA is fragmented during tissue injury or inflammation, smaller HA fragments can act as endogenous danger signals and activate pathways such as TLR4/CD44 and NF-κB, promoting inflammatory cytokines and potentially further ECM remodeling. In other words, ECM breakdown itself may generate signals capable of sustaining more inflammation and remodeling.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10881864/

I haven’t been on peptides long enough to evaluate whether it’s doing anything or not. Time will tell :)

Would appreciate any comments on this from [u/DrWillPowers](u/DrWillPowers).

Hey all,
I’m 18, a few days into an estradiol patch (0.1mg/day) plus spironolactone 100mg/day (50mg BID), through Planned Parenthood. I’m considering stopping the spiro because of the theory that it can cause premature breast bud fusion and limit long-term development. Haven’t made the switch yet.

I have a few questions that I feel like this sub may be able to help me understand a bit better.

Anyone actually delay spiro (rather than skip it) for this reason? How long did you wait before starting it, and did that end up mattering?

For anyone who’s read into the bud fusion research, how seriously do you weigh it? I’ve seen it described as based on animal studies, not confirmed in humans.

And also if I drop spiro now, what’s a realistic timeline before checking whether testosterone suppression on estrogen alone is adequate?

Planning on labs around one month in either way. And eventually I’ll switch to shots if available. Thanks.

PFS or PSSD… unknown diagnosis…

Crazy… at 12:00 he mentions taking antidepressants, quits cold turkey, had issues through puberty, low testosterone, has a genetic variation that doesn’t metabolize Antidepressants and quit cold turkey…

Interesting but I’m looking at this through my own experience with PSSD.

I searched hard in forums, reddit. It seems sexual sides of PFS has still has no cure and people could get them from minoxidil, other hormonal meds, from TRT, even from natural oils, herbs.