Enclomiphene Blunts IGF-1 by 48% While Boosting Testosterone

What Enclomiphene Might Be Doing to Your IGF-1

I actually learned something new about HDH, IGF-1, and colomaphene this week.

What that is, is when you take a colomaphene or any serum for that matter, it actually blunts the production of IGF-1 at the liver. I cannot point you to a study that pins that number down in men, so treat this as what I have been reading and thinking about rather than settled science.

The mechanism makes more sense once you have the whole loop in front of you.

Your brain runs testosterone through a feedback circuit. The hypothalamus signals the pituitary, the pituitary releases LH, the testes make testosterone, and some of that testosterone gets converted into estrogen by an enzyme called aromatase, which is the thing that turns androgens into estrogens.

That estrogen travels back to the brain and tells the system to ease off, the way a thermostat senses a room has warmed and tells the furnace to quiet down, with estrogen acting as the sensor.

If you don't know what in colomaphene or these serums are, what they do is they basically trick your body into thinking that your estrogen levels are low.

And what this does is it basically negates the feedback that your brain relies on to tell your body to throttle the production of testosterone. The drug sits in the estrogen receptor without switching it on, so the sensor reads cold even though the room is warm.

So when I take something like in colomaphene, my body thinks I don't have very high estrogen levels because it technically doesn't see them. The thermostat calls for more heat, LH climbs, testosterone follows.

Estrogen does not only act at the brain, either. In rams, Sanford showed it regulates testosterone through both a gonadotropin dependent route and a direct route at the testes, so there is more than one wire running through this loop.

But your body also relies on the presence of estrogen to convert growth hormone into IGF-1 at the liver. From what I have seen, that relationship gets stated far more confidently than the evidence supports, and no study has shown the exact conversion step people describe.

And when we take a serum, depending upon which serum it is, this can actually blunt the production of IGF-1 by up to 48%. The research hasn't given me a clean human number to hand you, so I am telling you what I have been chasing, not what is proven.

Here is why it matters even if the size of the effect is uncertain.

Growth hormone does very little on its own. It pulses out of the pituitary, reaches the liver, and only then does the liver produce IGF-1, which is the molecule actually driving tissue repair, muscle protein synthesis, and bone turnover.

So if liver output drops while pituitary output stays the same, a growth hormone reading on a blood panel can look completely normal while the downstream signal is quieter than it should be.

That is why checking GH alone tells you almost nothing.

If you are on enclomiphene or any SERM and you care about recovery, run an IGF-1 level. Get one before you start if you can, and another six to eight weeks in, same time of day, same lab.

If IGF-1 falls hard while testosterone climbs, you have a real tradeoff in front of you instead of a theory, and you can lower the dose, switch compounds, or decide the testosterone is worth it.

If IGF-1 holds steady, you have answered the question for your own body, which is the only body the answer needs to apply to.

The habit worth building is this. Any drug that works by hiding a hormone from one tissue is also hiding it from every other tissue reading the same signal, and estrogen is doing work at bone, at the liver, at the vasculature, and at the brain.

Blocking a receptor does not aim at one target. It lands everywhere the signal was ever read.

Research: Sanford LM, J Androl, 1985.

References:

Sanford LM. Evidence that estrogen regulation of testosterone secretion in adult rams is mediated by both indirect (gonadotropin dependent) and direct (gonadotropin independent) means. J Androl. 1985. https://pubmed.ncbi.nlm.nih.gov/3932290/

Lazier CB, Langley S, Ramsey NB et al.. Androgen inhibition of vitellogenin gene expression in tilapia (Oreochromis niloticus). Gen Comp Endocrinol. 1996. https://pubmed.ncbi.nlm.nih.gov/8954765/