Does HGH Shorten Your Lifespan? — Here's the Truth | Weekly Q&A

Watch the full video on Rumble: https://rumble.com/v7fugv2-does-hgh-shorten-your-lifespan-heres-the-truth-weekly-q-and-a.html

I have one more really important piece that's coming in next week that I'm waiting for, but I'm just going to go ahead and give you guys the current look at what we have now. Most of what follows comes down to one idea that shows up in three different hormone systems, so it makes sense to build the map before zooming into any single piece.

Your body runs testosterone and growth hormone on the same basic design. A signal comes from the brain, a gland downstream makes the hormone, and then something the hormone turns into travels back up to the brain and tells it to slow down. Break the feedback and you get more hormone. Bypass the gland entirely and you get whatever you inject, with nothing left to stop you.

For testosterone, the chain starts with GnRH from the hypothalamus, which triggers the pituitary to release luteinizing hormone and follicle stimulating hormone. Luteinizing hormone tells the testes to make testosterone, and follicle stimulating hormone handles sperm production.

That testosterone then converts into two other things. Some of it becomes estradiol through an enzyme called aromatase, which lives mostly in fat tissue, and adipose tissue dysfunction in obesity is a well documented driver of low testosterone in men for exactly this reason (Genchi 2022). Some of it becomes DHT through five alpha reductase, an enzyme that shows up in the prostate and also in the brain, where it has roles in neurosteroid production (Paba 2011).

When that estrogen is detected in your brain, that's what's creating the negative feedback to tell your body to stop producing more testosterone.

Blocking the estrogen receptors in the brain is exactly how clomiphene operates, since once the brain reads estrogen as lower than it actually is, it responds by pushing more GnRH, more luteinizing hormone, and more testosterone out the other end. A systematic review and meta analysis of clomiphene in hypogonadal men found consistent increases in total testosterone across studies (Huijben 2022), and there are documented cases of complete reversal of adult onset hypogonadotropic hypogonadism on clomiphene alone (Ioannidou-Kadis 2006).

There is a claim floating around that clomiphene does not suppress your natural production process. I cannot point you to a study that settles that question cleanly, so I am not going to state it as fact.

Where clomiphene actually fits is secondary hypogonadism, especially in guys who are overweight, sleeping badly, or under eating protein and calories, because the signal is intact and the problem is upstream.

But the second reason why in clomophene is a viable option or would be used is in a situation where it's a post-cycle therapy for somebody who's doing like a bodybuilding style, high dose testosterone with other anabolics, right? So we do our eight, 12, 16 week cycle blast, then we phase off, we go onto in clomophene and this helps our body to basically turn on that natural production.

For some men, clomiphene raises sex hormone binding globulin roughly in proportion to how much it raises free testosterone, and that shift is the downside almost nobody brings up when they talk about this drug. SHBG is a protein in the blood that grabs free testosterone and holds it so it cannot bind to androgen receptors, so the number on the page climbs while the way you actually feel stays flat and unchanged.

And if that's the case, a lot of times just moving over to regular testosterone replacement is a better approach because that SHBG problem doesn't occur with TRT. So if you want to move from in clomophene directly to TRT, there's technically nothing that's going to stop you from like doing that in the same day, right? Like there's no conflict there. Clomiphene's mechanism and TRT's mechanism do not fight each other, and clomiphene is well characterized as an alternative rather than a competitor to replacement therapy (Wu 2024).

Some guys avoid TRT because of fertility and stay on clomiphene for years with elevated SHBG. In my opinion, that's way worse of an option than just adding HCG. So if going on to testosterone, your concern is fertility, just add like 500 IU of HCG three times a week and your testicles won't atrophy while you're on the TRT and you'll have no problem having kids.

The lifespan question runs on the same logic as the SHBG question, which is that the dose decides everything and the word on the label decides nothing.

And there are so many guys that I've had to explain to like TRT doses of testosterone and we'll say pro bodybuilding doses of testosterone are two completely different things, right? So like a therapeutic dose of testosterone, we'll say around 200 to 250 milligrams per week, at best bring a guy into like an optimal range, somewhere around a thousand nanograms per deciliter, where like the average pro bodybuilder is doing like five times that in some cases.

One of those is bringing a man back into a range his own body could have produced. The other is a gram a week of something with labs reading off the chart. So that's like something that we've had to work through in the TRT industry, I would say over the past, you know, four or five years that I think we're finally almost through.

The same basic loop governs growth hormone, just with different players running the circuit. GHRH comes out of the hypothalamus, the pituitary releases growth hormone, the liver converts it into IGF-1, and IGF-1 travels back up and raises somatostatin, which puts the brake on GHRH. The function that estrogen serves in testosterone feedback is what somatostatin is doing for growth.

So when we're talking about the use of like, we'll say growth hormone, if you're staying below four IU per day, your IGF-1 levels aren't really going to go much greater than 400.

And when we talk about the risk that's associated with your IGF-1 levels, it's really above 400 where you start to see problems for in terms of risk reward, right? For the average guy who's just looking to optimize his health, feel good, perform better.

A dose of around two to four IU per day is going to get your IGF-1 levels somewhere between two and 400. Three to 400 is the window I want.

Injected growth hormone goes around the pituitary completely, which is how you climb above anything your body would have produced on its own. Secretagogues cannot do that, because they still push through the pituitary and somatostatin still applies the brake.

Tesamorelin replicates the GHRH signal and works on its own. The EGRIFTA trials that took it through FDA approval ran it as a monotherapy over 52 weeks with no meaningful loss of growth hormone production, meaning the GHRH receptors at the pituitary do not appear to desensitize. Ipamorelin works differently, inhibiting somatostatin at the pituitary so the pulse comes out bigger.

Like these two together are what are going to like really send the improvements to your IGF-1 levels over the top when it comes to growth hormone peptides.

Ghrelin receptors do desensitize, which we know from the hexarelin work, so ipamorelin comes off every 12 weeks for at least eight weeks while tesamorelin stays on.

So with all that said, is there a risk associated to optimizing your growth hormone IGF-1 levels? Yes, of course there's a risk to everything. The risk lives above 400, and the whole point of staying under four IU is that you never get there.

The dose problem gets sharper with women, because the target range is tiny. Now for context, the reference range that we're looking for for a man is I'm going for like 500 is the average for a guy, and most men do not perform well until they are over 800. For a woman the range is 15 to 70 nanograms per deciliter.

Now with that said, what are the better approaches? Well, if I'm a man and I'm doing TRT, typically like a dose of 125 to 150 milligrams would be a starting dose per week. And that's usually going to put him at about, you know, we'll say 800 to 1200 nanograms per deciliter.

A woman needs one to three units per week. And so the only argument against using injection for women, even though it's much more accurate, it's much more predictable, I can control it is the fact that like testosterone typically only comes in larger 200 milligram per milliliter vials, which is that's the concentration of it.

Research: Genchi 2022, Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism; Paba 2011, Steroid 5α-reductase as a novel therapeutic target; Huijben 2022, Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis; Ioannidou-Kadis 2006, Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate; Wu 2024, Clomiphene Citrate Treatment as an Alternative Therapeutic Approach for Male Hypogonadism.

References:

Genchi VA, Rossi E, Lauriola C et al.. Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism. Int J Mol Sci. 2022. https://pubmed.ncbi.nlm.nih.gov/35897769/

Wu Y, Godoy A, Azzouni F et al.. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors. Prostate. 2013. https://pubmed.ncbi.nlm.nih.gov/23813697/

Paba S, Frau R, Godar SC et al.. Steroid 5α-reductase as a novel therapeutic target for schizophrenia and other neuropsychiatric disorders. Curr Pharm Des. 2011. https://pubmed.ncbi.nlm.nih.gov/21361868/

Wu YC, Sung WW. Clomiphene Citrate Treatment as an Alternative Therapeutic Approach for Male Hypogonadism: Mechanisms and Clinical Implications. Pharmaceuticals (Basel). 2024. https://pubmed.ncbi.nlm.nih.gov/39338395/

Ioannidou-Kadis S, Wright PJ, Neely RD et al.. Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate. Fertil Steril. 2006. https://pubmed.ncbi.nlm.nih.gov/17070201/

Huijben M, Lock MTWT, de Kemp VF et al.. Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis. Andrology. 2022. https://pubmed.ncbi.nlm.nih.gov/34933414/