HCG vs Enclomiphene vs Kisspeptin vs Gonadorelin - How do men make Testosterone?
Chris Neal uses a diagram of the brain-to-testicle hormone cascade to explain where kisspeptin, gonadorelin, HCG and enclomiphene each act during testosterone replacement therapy.
With Chris Neal
Key moments
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- 0:00Four TRT medications introducedNeal says HCG, clomiphene, kisspeptin and gonadorelin are common in TRT and that there is no single right choice because people differ. He plans to explain the science with a diagram.
- 1:06Kisspeptin starts the cascadeNeal explains that kisspeptin neurons in the hypothalamus start the whole process. He says supplementing kisspeptin boosts that first step and that its short half-life means frequent dosing.
- 3:04Gonadorelin as the GnRH signalHe says kisspeptin switches on the neurons that release GnRH, the first signal to leave the hypothalamus. Injecting gonadorelin, which is GnRH, strengthens that signal.
- 4:20Pituitary, LH, FSH and testiclesNeal describes pituitary cells responding to GnRH by releasing LH and FSH. He says these keep the testicular factory running and that it shuts down and shrinks when the signal stops.
- 6:11HCG as a stand-in for LHHe says HCG is structurally similar to LH and FSH and acts like a replacement key. He then criticizes pressure on compounding pharmacies, which he says make it the same way as the brand version.
- 7:38Testosterone converts to DHT or estrogenNeal says testosterone can stay as it is, become DHT, or become estrogen. He mentions aromatase inhibitors such as anastrozole and letrozole and says the balance of estrogen is tricky.
- 9:27Estrogen as the off switchHe argues that estrogen, rather than testosterone, signals the hypothalamus to shut down GnRH. Enclomiphene blocks that signal, which he says lets the cascade keep running while on testosterone.
- 11:30Dosing balance and combining optionsNeal says enclomiphene must be dosed against the estrogen level in the body and works best alongside proper aromatase inhibitor use. He says the options act differently and can sometimes be combined under medical guidance.
What the video says
Chris Neal, who talks about patients at his clinic, Vivo Health Solutions, presents a diagram of the signaling chain that leads to testosterone production. His point is that people on medically managed testosterone replacement therapy (TRT) usually have a weak link somewhere in that chain. He says it can be hard to tell which step is the problem, so the best-suited medication differs from person to person.
He starts at the top. Kisspeptin neurons in the hypothalamus make kisspeptin, which switches on the neurons that make gonadotropin releasing hormone (GnRH), also called gonadorelin. Neal says supplementing kisspeptin boosts the very first step, and that it has a short half-life, so it needs more frequent dosing than twice a week for most people. Gonadorelin is the same molecule as GnRH, so he describes injecting it as strengthening the signal sent from the hypothalamus to the pituitary.
Next he covers the pituitary, where GnRH prompts cells to release LH and FSH, which travel to the testicles. He describes the testicles as a factory that keeps running as long as it receives that signal, producing testosterone and sperm and contributing to sexual sensitivity. He says HCG resembles LH and FSH closely enough to act as a stand-in key, restarting that factory. He also spends time on why HCG has been hard to get from compounding pharmacies in the United States, which he attributes to pharmaceutical company pressure.
The last section covers what happens to testosterone once it is in the blood. Neal says it can stay as testosterone, become DHT, or convert to estrogen, and that aromatase inhibitors are used to limit the conversion. He argues that estrogen, not testosterone, is what tells the hypothalamus to shut the cascade down. Enclomiphene, a pill, blocks that estrogen signal, and he says it has very few side effects. He stresses that dosing has to match estrogen levels and that a medical professional should guide any combination.
On each compound
Kisspeptin-101:06
Neal says kisspeptin is made by neurons in the hypothalamus and starts the testosterone cascade. He says supplementing it boosts that first step, and that its short half-life means it needs to be used more often than twice a week for most people.
See how your DNA reads Kisspeptin-10Gonadorelin3:04
Neal says gonadorelin is the same as GnRH, the first signal leaving the hypothalamus for the pituitary. He describes injecting it as boosting that signal when it is the weak step in the cascade.
See how your DNA reads GonadorelinWhat this video doesn’t settle
- It is one clinician's explanation from a diagram, with no studies, trial data or doses cited for any of the four medications.
- Neal runs a TRT clinic that sells kits including these medications, so the video also serves as promotion for his business.
- He gives no way to tell which step of a person's cascade is the problem, and no comparison of how well each option works.
Questions this video answers
How does kisspeptin relate to testosterone production?
Neal says kisspeptin neurons in the hypothalamus start the cascade by switching on the neurons that release GnRH. He says supplementing kisspeptin stimulates the very first step and, because of its short half-life, is used more often than twice a week.
What is the difference between gonadorelin and HCG?
According to Neal, gonadorelin is GnRH and acts at the hypothalamus to pituitary step. HCG acts further down, mimicking LH and FSH to stimulate the testicles directly.
Why does testosterone therapy shut down the body's own production, according to Neal?
Neal argues that testosterone itself does not flip the switch off. He says some of it converts to estrogen, and the hypothalamus senses that estrogen and shuts down GnRH, which stops everything downstream.
How does enclomiphene work in this video?
Neal says enclomiphene is a pill that blocks the estrogen sensing switch in the hypothalamus, so the cascade keeps running during TRT. He says it is a cleaner version of clomiphene with few side effects, and that its dose must be balanced against estrogen levels.
What does Neal say about HCG availability?
Neal says HCG is not banned in the United States but that compounding pharmacies have been pushed out, which he attributes to money rather than safety. He says he expects it to return, as it has after earlier restrictions.
Video by Real Science with Chris Neal on YouTube, embedded as published. The summary is written by PeptidesDNA from the video; every claim in it is the speaker’s. Not affiliated with or endorsed by the creator. Not medical advice.
