Kisspeptin or TRT for Low Testosterone? (What to Try First)

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Kisspeptin or TRT First for Low Testosterone: What Actually Happens Upstream

What protocol do you recommend first for low testosterone? KissPeptin or TRT? All right, so I've done videos on this and I'm just gonna kind of briefly touch on this because I think it's a common question in KissPeptin, especially in the, you know, we'll say that the realm of peptides is becoming an increasingly more popular peptide that people wanna try specifically for their HPG axis.

Before comparing them, you need the whole chain in your head, because the two options act at completely different points on it.

The downside of KissPeptin is that it creates desensitization at the receptor in the hypothalamus, okay? And so if you don't know what KissPeptin is, it's actually sitting above your HPG axis, meaning KissPeptin is, those receptors are what are basically triggering your hypothalamus to release gonadotropin, releasing hormone, which then in turn goes to pituitary, produces LH and FSH, which then go to the testicles or the ovaries, depending upon whether you're a man or a woman.

That makes kisspeptin the most upstream lever available, and the neurons carrying it also read your energy status, which is why low body fat and low food intake shut reproductive signaling down before anything lower in the chain even gets a message (Navarro 2020).

This is 100% true. But the studies show that in order for this to have any meaningful effect for long term, it actually needs to be dosed very frequently. Continuous or heavy exposure at that receptor blunts the response, which is the same behavior seen with GnRH itself, where pulses stimulate and steady signal suppresses (Prague 2015).

So the whole system runs on rhythm, not on volume, and your body is deliberately turning the signal on and off rather than holding it open.

And so in a situation where you're trying to use KissPeptin specifically to optimize your natural testosterone, you're kind of in a weird situation because at most you can only dose the KissPeptin every other day.

And so what we're doing is we're creating this peak and trough of the production of GnRH from our brain from the KissPeptin by doing it every other day.

Picture a thermostat that only gets checked on alternate days. The house still heats, but it swings, and testosterone swinging is what people feel as mood dropping off, libido going quiet, and energy going flat midweek even though a lab draw on a good day looks fine.

So in my opinion, if you're gonna go the route with KissPeptin, it needs to be paired with something that's also functioning or influencing downstream impacts, such as HCG or enclomaphene. The reason is structural: HCG acts directly at the testicle and enclomiphene acts at the pituitary, so they fill the trough while the upstream signal is off.

And in that case, specifically with enclomaphene, you're gonna be looking at issues related to raised SHBG, which is gonna affect your overall free test. I cannot point you to a study that settles that question cleanly, so treat that as what I watch for in bloodwork rather than something the literature has closed the book on, and it matters because SHBG binds testosterone and the bound portion is not available to your tissues. Total can rise while free sits still.

Some men respond well to that stack. It can get them within seven, 800 naturally without having to do TRT. But in my opinion, if you're looking to add something, TRT is gonna be the easiest route, but also be advised that it's also gonna create the suppression. From what I have seen, both of those outcomes hold up in practice, though no study has shown either one in the combination and dosing patterns people actually run.

There is a lot more of this inside the free community, and it is genuinely free, so if you want somewhere to ask the follow-up question the men's group is here: https://www.skool.com/jh-iron-forge-brotherhood/about

Research: Spaziani M et al., Mol Cell Endocrinol 2021; Navarro VM, Nat Rev Endocrinol 2020; Prague JK & Dhillo WS, Neuroendocrinology 2015.

References

Spaziani M, Tarantino C, Tahani N et al.. Hypothalamo-Pituitary axis and puberty. Mol Cell Endocrinol. 2021. https://pubmed.ncbi.nlm.nih.gov/33271219/

Navarro VM. Metabolic regulation of kisspeptin - the link between energy balance and reproduction. Nat Rev Endocrinol. 2020. https://pubmed.ncbi.nlm.nih.gov/32427949/

Prague JK, Dhillo WS. Potential Clinical Use of Kisspeptin. Neuroendocrinology. 2015. https://pubmed.ncbi.nlm.nih.gov/26277870/