Lose Skin: HGH/Secretagogues?

[Mushy404]

Hi all,

Regarding loose skin, would you say there's significant benefit to using HGH/Secretagogues throughout the fat loss process for those losing significant fat?

I understand that it likely wont avoid loose skin completely for those losing a lot of fat, and surgery to get rid of it is likely going to be required in some form.

It's my understanding that HGH stimulates:

• IGF‑1 → increases fibroblast activity → promotes collagen + elastin synthesis in the dermis
• Protein synthesis + nitrogen retention → supports muscle growth, which helps "fill out" skin
• Cell turnover and skin thickness
• Improves hydration and dermal volume

Constructive, thoughts?
Any alternatives?

My research has also led me to things like:
- Topicals: tretinoin (Boosts collagen synthesis, increases cell turnover, reduces fine wrinkles, stretch marks, and skin thinning)
- Microneedling or ultrasound on problem areas,Improving skin elasticity and firmness)

 

[songsofpyramids]

If you’re loosing substantial weight there is unfortunately very little one can do to mitigate loose skin.

Go post an intro, share more information (height, weight, drugs you’re on, etc) and you’ll get more substantial help. It is hard for people to chime in with so little info.

 

[Mushy404]

If you’re loosing substantial weight there is unfortunately very little one can do to mitigate loose skin.

Go post an intro, share more information (height, weight, drugs you’re on, etc) and you’ll get more substantial help. It is hard for people to chime in with so little info.

Thanks for the reply.

For me, it's not a query on whether I can prevent lose skin (I'm going to get it), but rather how I can reduce it.

I'm 38, male and somewhere around 375lbs at 5ft 10 (180cm).
I was 410lbs at my heaviest about 1 year ago but wasnt at that weight for long. Got down to 370 with just a keto diet, but recently went up to 390lbs.

Currently taking Retatrutide, started 2 weeks ago, currently at 2mg/week but bumping up to 4mg in a few days.

From my research, it is my understanding that HGH and Secretagogues can help reduce the amount of lose skin I get, along with a topical called tretinoin.

Taken from my original post...
It's my understanding that HGH stimulates:

• IGF‑1 → increases fibroblast activity → promotes collagen + elastin synthesis in the dermis
• Protein synthesis + nitrogen retention → supports muscle growth, which helps "fill out" skin
• Cell turnover and skin thickness
• Improves hydration and dermal volume

 

[adrenalytic]

Thanks for the reply.

For me, it's not a query on whether I can prevent lose skin (I'm going to get it), but rather how I can reduce it.

I'm 38, male and somewhere around 375lbs at 5ft 10 (180cm).
I was 410lbs at my heaviest about 1 year ago but wasnt at that weight for long. Got down to 370 with just a keto diet, but recently went up to 390lbs.

Currently taking Retatrutide, started 2 weeks ago, currently at 2mg/week but bumping up to 4mg in a few days.

From my research, it is my understanding that HGH and Secretagogues can help reduce the amount of lose skin I get, along with a topical called tretinoin.

Taken from my original post...
It's my understanding that HGH stimulates:

• IGF‑1 → increases fibroblast activity → promotes collagen + elastin synthesis in the dermis
• Protein synthesis + nitrogen retention → supports muscle growth, which helps "fill out" skin
• Cell turnover and skin thickness
• Improves hydration and dermal volume

Yes, HGH does do all that but it is a long game. You won't notice it immediately. Several months of daily dosing is required. Also, congrats on the weight loss but that is an enormous amount body fat at that height. I wouldn't expect GH to be noticeable at all for you but everyone is built differently. Pics could help us judge better but you will likely need surgery. The good news is that insurance will typically cover it if it is severe enough.

Anecdotally speaking, I am 5'9" and went from 260 lbs (40% bf) down to 180 (~9% bf) in a very short time and daily use of GH is just now beginning to show signs of skin tightening after 8 months of consistent dosing.

 

[roofer22]

I lost 150 pounds in a year. No peptides or drugs or anything besides surgery is going to help with that much extra skin. Mines not horrible considering. It does cover my lower abs though so only a four pack for me.

 

[Mushy404]

Yes, HGH does do all that but it is a long game. You won't notice it immediately. Several months of daily dosing is required. Also, congrats on the weight loss but that is an enormous amount body fat at that height. I wouldn't expect GH to be noticeable at all for you but everyone is built differently. Pics could help us judge better but you will likely need surgery. The good news is that insurance will typically cover it if it is severe enough.

Anecdotally speaking, I am 5'9" and went from 260 lbs (40% bf) down to 180 (~9% bf) in a very short time and daily use of GH is just now beginning to show signs of skin tightening after 8 months of consistent dosing.

Thanks for the input.

So did you wait until after you lose the weight to start the GH? Also, what dose you taking? 3IU?


I understand that it's a long game, which is why I am asking now before the weight is lost and can be running along side the fat loss.

I find the cost of the HGH/Secretagogues I am considering running to be affordable and to be honest it's a drop in the ocean compared to how much the surgery is going to cost me - I am in the UK, my insurance aint covering shit! And the public medical (NHS) system are unlikely do do anything either, and if they do, I'll be waiting years on it.

When I get to the point where I have the inevitable loose skin, I am probably going to have to maintain that weight for 6 months or more before getting the surgery, so if I have to live 6+ months with that, then any significant reduction in loose skin as a result of running HGH/Secretagogues as I lose the weight, it gonna be worth it for me.

Ideally we'd be able to quantify how much HGH/Secretagogues and tretinoin will help, but this is going to be impossible to do accurately as there are so many factors.

I will never actually know how much the HGH/Secretagogues and tretinoin helped when running along side fat loss, but I guess just knowing they will help to some extent would be good enough for me.

 

[Mushy404]

According to my research, in terms of lose skin reduction, running Tesamorelin and Ipamorelin along side the fat loss would have better results than running just the GH for the same period (48 weeks).

Autophagy appears to be blunted (via chronic mTOR/IGF-1) if using HGH for the full 48 weeks.

Tesamorelin + Ipamorelin → Pulsatile GH → Supports Autophagy​

• Tesamorelin (a GHRH analog) causes sharp GH pulses and raises IGF-1 without suppressing natural secretion.
• Ipamorelin synergistically boosts GH amplitude without cortisol/prolactin spikes.
• Animal studies show GH pulses (natural or mimicked) activate hepatic and skin autophagy, particularly during fasting.

Key Mechanistic Evidence:

• Pulsatile GH increases LC3-II expression, a key autophagy marker.
  (Cai et al., 2015 – mice; PMID: 25675517)
• Tesamorelin raises GH + IGF-1 while improving insulin sensitivity — a state known to favor autophagy.
  (Stanley et al., JCEM 2011; PMID: 20943777)

============================================

HGH (Exogenous) → Constant GH → Inhibits Autophagy (in some tissues)​

• Chronic GH exposure activates mTORC1 and suppresses autophagy in liver, pancreas, and skin.
• Even at moderate doses (e.g., 3 IU/day), HGH reduces AMPK signaling, opposing the autophagic environment seen in fasting.

Key Evidence:

• GH overexpression mice show impaired autophagy and accelerated aging.
  (Cheng et al., 2014 – PMID: 24368315)
• Chronic GH infusion in humans increases IGF-1 and body mass but blunts FFA release and insulin sensitivity.
  (Møller et al., JCEM 1995; PMID: 7543114)

 

[Mushy404]

Conclusion​

While no study directly compares Tesamorelin + Ipamorelin vs. HGH for autophagy, multiple lines of evidence — animal data, human endocrine trials, and mechanistic pathways — support the idea that T/I is more favorable for autophagy due to:

• Pulsatile GH signaling
• Preserved insulin sensitivity
• Lower chronic mTOR activation

If autophagy is a core therapeutic target (loose skin, anti-aging, fasting synergy), the T/I stack is superior in theory and mechanistic support, even if direct human biopsy data isn’t yet available.​

 

[songsofpyramids]

I don’t mean to the bearer of bad news but hgh, secretagogues, and tretinoin are going to do very very little to help with your skin looseness from extreme weight loss. My buddy lost 100lbs while doing hgh, dry brushing, and tretinoin, and he still needs skin surgery and it does not appear to have meaningfully reduced skin looseness. The unfortunate reality is that when loosing extreme amounts of weight there is very little one can do to mitigate loose skin.

 

[Mushy404]

I don’t mean to the bearer of bad news but hgh, secretagogues, and tretinoin are going to do very very little to help with your skin looseness from extreme weight loss. My buddy lost 100lbs while doing hgh, dry brushing, and tretinoin, and he still needs skin surgery and it does not appear to have meaningfully reduced skin looseness. The unfortunate reality is that when loosing extreme amounts of weight there is very little one can do to mitigate loose skin.

Did he employ these from the beginning of losing fat?

Just to be crystal clear, I KNOW I am going to have lose skin. I am not looking for a way to avoid it - that's impossible.

I am looking for a way to reduce it, particularly on the parts of the body which may be salvageable, or where even a modest reduction in what lose skin I otherwise would have makes all the difference.

The aim for this thread was to discuss whether HGH/Secretagogues can help, and there was a hope - perhaps naively - that we could come close to quantifying the benefit. So as it stands, unless someone can provide evidence to the contrary of the research I just posted, then I guess my plan is to follow it - albeit doing a bit more research between now and then

 

[adrenalytic]

Thanks for the input.

So did you wait until after you lose the weight to start the GH? Also, what dose you taking? 3IU?


I understand that it's a long game, which is why I am asking now before the weight is lost and can be running along side the fat loss.

I find the cost of the HGH/Secretagogues I am considering running to be affordable and to be honest it's a drop in the ocean compared to how much the surgery is going to cost me - I am in the UK, my insurance aint covering shit! And the public medical (NHS) system are unlikely do do anything either, and if they do, I'll be waiting years on it.

When I get to the point where I have the inevitable loose skin, I am probably going to have to maintain that weight for 6 months or more before getting the surgery, so if I have to live 6+ months with that, then any significant reduction in loose skin as a result of running HGH/Secretagogues as I lose the weight, it gonna be worth it for me.

Ideally we'd be able to quantify how much HGH/Secretagogues and tretinoin will help, but this is going to be impossible to do accurately as there are so many factors.

I will never actually know how much the HGH/Secretagogues and tretinoin helped when running along side fat loss, but I guess just knowing they will help to some extent would be good enough for me.

I started with 2IU but have been bouncing around between 3-5 IU depending on severity of CTS symptoms.

Forget the secretagogues. They are only worth it for the very young. You sound very budget conscious so just funnel your money into HGH. Even if you don't get the skin benefits you will get the fat burning and body recomp benefits. Just be sure to keep an eye on your insulin sensitivity. At your weight I'll hazard a guess you are quite resistant. Address this before getting on HGH or just be sure to only use it at night 3 hours postprandial. I would still get a BGM if you don't have one already.

I have no experience with tretinoin so I'll let others speak to that.

Also, simply asking ChatGPT about something is not research. Go read the citations it provided and make sure it is consistent and current (some of those citations are quite old) with what was summarized. If you did this already then kudos to you. Most people don't.

 

[SpicyMeatball]

Take the money you’d spend on gh and start a cosmetic surgery fund. You’re going to need surgical removal if you achieve such massive weight loss, gh will make no difference to that fact so might as well just start saving.

 

[songsofpyramids]

Take the money you’d spend on gh and start a cosmetic surgery fund.

This is the most solid advice in the thread. Hgh is the icing on top of the cake once you have everything else on the cake dialed in. I truly feel its impact will be negligible for someone at the beginning of weight loss like op, and if op’s insulin sensitivity is already bad (very possible) than the hgh could end up being a net negative.

Did he employ these from the beginning of losing fat?

He used them the entire time.

 

[Mushy404]

I started with 2IU but have been bouncing around between 3-5 IU depending on severity of CTS symptoms.

Forget the secretagogues. They are only worth it for the very young. You sound very budget conscious so just funnel your money into HGH. Even if you don't get the skin benefits you will get the fat burning and body recomp benefits. Just be sure to keep an eye on your insulin sensitivity. At your weight I'll hazard a guess you are quite resistant. Address this before getting on HGH or just be sure to only use it at night 3 hours postprandial. I would still get a BGM if you don't have one already.

I have no experience with tretinoin so I'll let others speak to that.

Also, simply asking ChatGPT about something is not research. Go read the citations it provided and make sure it is consistent and current (some of those citations are quite old) with what was summarized. If you did this already then kudos to you. Most people don't.

Thanks for the info.

I am not budget conscious. However, for me (and I would assume most people?) the Tesa/Ipa protocol would be cheaper than the GH for the same period of time. But as I said, not budget conscious.

The fat loss is under control already as I am on Retatrutide. My point of concern as it relates to this thread is loose skin. So while I appreciate the sentiment in saying that even if I don't get the skin benefits from the HGH at least get the fat loss - I'll get the fat loss from the GLP regardless.

Agreed on some of my citations being dated, but unfortunately we gotta make do with older research sometimes, as more current research isnt always there. Plus, our bodies largely work the same as they did 100 years ago, so older studies aren't necessarily useless. "In the land of the blind, the one eyed man is king". So to speak. Though I would absolutely prefer more recent.

Possibly a silly question, but what's BGM?

 

[Mushy404]

Take the money you’d spend on gh and start a cosmetic surgery fund. You’re going to need surgical removal if you achieve such massive weight loss, gh will make no difference to that fact so might as well just start saving.

Thanks for the input - sound advice on the surgery fund!
I've already been working on it and thankfully I am in a financial situation where I don't have to chose from 1 of the other. I can do both.

 

[songsofpyramids]

Tesa will absolutely be more expensive than generic hgh. Regardless, neither are going to do what you’re hoping. If they mitigate the loose skin it will likely be to an imperceptible amount. IMO the best thing you can do for you loose skin right now is supplement collagen and focus on getting in as much clean bioavailable proteins as possible while loosing weight. I think you are underestimating the health issues you could run into doing these substances while being morbidly obese. They make you hold water which can stress your already stressed body. They can raise prolactin and increase estrogen, both of which are likely already not great for you due to your weight.


Are your hormones being managed already? Do you have a baseline of what’s happening in your body via bloodwork? Do you have baseline igf1? How’s your a1c? Have you checked your test? Are you on trt? What other drugs are you doing?


Why I suggested you to make an intro is that you’ve got a site literally brimming with people who can help you in your quest, but you’re not giving people the information they need to help you.

 

[Mushy404]

This is the most solid advice in the thread. Hgh is the icing on top of the cake once you have everything else on the cake dialed in. I truly feel its impact will be negligible for someone at the beginning of weight loss like op, and if op’s insulin sensitivity is already bad (very possible) than the hgh could end up being a net negative.


He used them the entire time.

I'd agree with you that I am insulin resistant. However, I am on a ketogenic diet, on Retatrutide, and for the last 3 weeks was trying out Tesa/Ipa in regards to improving sleep mainly - all of these Improve insulin resistance. And of course the fat I've been losing. Granted it takes more than a month to dramatically improve insulin resistance.

Interestingly, I am about to move from TRT gel to TRT injection tonight, so in 8 weeks I'll be getting a blood test. This includes HbA1c - and though it's not a direct indicator of insulin resistance, it does provide clues. I'll start a thread soon for my fat loss progress, and will update there any changes in my bloods since my last test.

 

[adrenalytic]

Why 8 weeks? Why don't you have baseline numbers already? Is this self-prescribed TRT? (I'm guessing yes bc a doctor would order bloodwork first and if your doctor hasn't then find a new one). Every 4-6 week blood testing is the gold standard for exogenous hormones especially if you're morbidly obese. 8 weeks can be fine if you're dialed in and stable. You are not. More fat=more aromatizing, higher BP, worse lipids and a host of other issues caused by obesity. Retatrutide will not save you from these things.

BGM = Blood glucose monitor. Get one.

 

[Mushy404]

Tesa will absolutely be more expensive than generic hgh. Regardless, neither are going to do what you’re hoping. If they mitigate the loose skin it will likely be to an imperceptible amount. IMO the best thing you can do for you loose skin right now is supplement collagen and focus on getting in as much clean bioavailable proteins as possible while loosing weight. I think you are underestimating the health issues you could run into doing these substances while being morbidly obese. They make you hold water which can stress your already stressed body. They can raise prolactin and increase estrogen, both of which are likely already not great for you due to your weight.


Are your hormones being managed already? Do you have a baseline of what’s happening in your body via bloodwork? Do you have baseline igf1? How’s your a1c? Have you checked your test? Are you on trt? What other drugs are you doing?


Why I suggested you to make an intro is that you’ve got a site literally brimming with people who can help you in your quest, but you’re not giving people the information they need to help you.

As mentioned earlier, I will make a thread for my progress soon. In that I will include previous blood results I've had for my TRT.

Also, I apologise, you are correct. HGH is about half the price at 3 IU per day than the T/I combo. Brain fart.

Valid point regarding water retention on GH, though much less of an issue on Tesa/Ipa. I'll be monitoring my bloods anyway, so we can see what's what on the progress thread as the weeks/months go by.

 

[Mushy404]

Why 8 weeks? Why don't you have baseline numbers already? Is this self-prescribed TRT? (I'm guessing yes bc a doctor would order bloodwork first and if your doctor hasn't then find a new one). Every 4-6 week blood testing is the gold standard for exogenous hormones especially if you're morbidly obese. 8 weeks can be fine if you're dialed in and stable. You are not. More fat=more aromatizing, higher BP, worse lipids and a host of other issues caused by obesity. Retatrutide will not save you from these things.

BGM = Blood glucose monitor. Get one.

Ah, haha, duh me!
Yep, I have a blood glucose monitor.

No, I am on legitimate TRT, I have been getting bloods for the last 6 months since I started TRT.

8 weeks was in relation to checking my bloods after switching from Gel to injectable. The have me on Anastrazole for my E2, which is in check.