TRT Clinic Revenue Loop

Your liver does not produce IGF-1 on its own schedule. It produces IGF-1 in response to a signal, and that signal depends on more than just growth hormone.

Here is the full chain before we zoom in on any single part of it. You take testosterone. Some of that testosterone converts into estrogen through a process called aromatization, which is just the body using an enzyme called aromatase to chemically transform one hormone into another. That estrogen travels to the liver. The liver uses it as part of the machinery that converts growth hormone into something called IGF-1, which stands for insulin-like growth factor 1 and is the molecule your body actually uses to build and repair tissue. More estrogen in the right range means more IGF-1 production. That is the chain.

Now here is where the revenue loop enters.

A TRT clinic puts you on testosterone. Your estrogen goes up because aromatization is working exactly as it should. The clinic sees elevated estrogen on your labs and prescribes an aromatase inhibitor, which is a drug that blocks the aromatase enzyme and lowers estrogen. Your estrogen drops. Your liver loses the signal it needs to convert growth hormone into IGF-1. Your IGF-1 collapses. The clinic offers you IGF-1. They created the deficiency and sold you the correction.

The mechanism behind why estrogen matters for IGF-1 is worth understanding because it is not obvious. Estrogen does not produce IGF-1 directly. What it does is upregulate the sensitivity of the liver to growth hormone, meaning it makes the liver more responsive to the signal that triggers IGF-1 production. Without adequate estrogen, growth hormone can still be present but the liver simply does not respond to it at the same rate. The signal arrives and the door is closed.

A randomized controlled trial published in 2017 by Dias and colleagues tested this directly in 37 men over the age of 65. One group received testosterone gel. Another group received an aromatase inhibitor. The testosterone group saw their IGF-1 increase by 15.3 nanograms per milliliter over the course of the study, because the testosterone was aromatizing into estrogen and that estrogen was driving liver conversion of growth hormone into IGF-1. The aromatase inhibitor group saw an increase of 0.3 nanograms per milliliter. Same population, same study design, same starting point. The only variable was whether estrogen was allowed to rise or was suppressed.

That 0.3 versus 15.3 comparison is what the mechanism looks like in real numbers.

Now, you might be thinking that elevated estrogen in men is a genuine clinical concern and that some estrogen management is medically reasonable. That is partially correct, and it is worth being precise here. Estrogen in men does have an upper range beyond which real symptoms occur, and estrogen management is not inherently wrong in concept. The problem is the frequency and the default with which aromatase inhibitors are being prescribed. A 2020 survey by Butaney and colleagues of 489 physicians asked about their estrogen management practices during TRT. 69.4 percent reported prescribing aromatase inhibitors for symptomatic elevated estrogen. Neither the Endocrine Society nor the American Urological Association, which are the two primary professional bodies that issue clinical guidelines on testosterone therapy, recommend routine aromatase inhibitor use for estradiol management during TRT in their 2018 guidelines.

So the majority clinical practice is running ahead of the evidence and the professional guidance.

Then there is the question of what IGF-1 replacement actually is. The FDA approved version of injectable IGF-1 is called mecasermin, sold under the name Increlex, and it carries an orphan drug designation, which means it was developed specifically for a condition so rare that no commercial market would otherwise fund it. That condition is called growth hormone insensitivity, sometimes called Laron syndrome, and it affects roughly 350 to 500 people worldwide. In these individuals, the pituitary releases normal growth hormone but the liver cannot respond to it due to a receptor defect, so IGF-1 never gets produced regardless of how much growth hormone is present. The FDA approval is specifically for children with this condition. It is not approved for adult men on testosterone therapy whose estrogen was suppressed by a prescription they received at a clinic.

The practical implication here is straightforward. If you are on testosterone and an aromatase inhibitor, get your IGF-1 tested. The number will tell you whether estrogen suppression has pulled IGF-1 down with it. If a clinic has offered you IGF-1 as a next step without examining whether their own aromatase inhibitor prescription is the reason your levels dropped, you are looking at either a gap in understanding or an intentional system.

The deeper issue is that none of this is hidden. The mechanism is documented. The 2017 Dias trial is not obscure literature. The AUA and Endocrine Society guidelines are public. Any clinician prescribing aromatase inhibitors routinely during TRT has access to the same data showing what happens to IGF-1 when you do that.

Most people think of hormone therapy as a matter of getting levels into range. But ranges do not exist in isolation. Suppressing one hormone changes the behavior of pathways that depend on it, and those downstream effects are where the real consequences live. The question to ask of any protocol is not just what this intervention corrects, but what it disrupts in the process of correcting it. That single question is what makes it very hard to sell someone a problem disguised as a solution.

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References

1. **Dias JP et al.** "Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men." *Metabolism*, 2017; 69:143-147. PMID: 28285644. RCT, 37 men aged 65+. Testosterone group: +15.3 ng/mL IGF-1. AI group: +0.3 ng/mL.
2. **Butaney M et al.** "Treatment of estrogen levels in the management of hypogonadism: An anonymous survey of ISSM members." *Urology*, 2020; 141:68-74. PMID: 32045591. 69.4% of 489 surveyed physicians prescribed AIs for symptomatic elevated estrogen.
3. **FDA Label (NDA 021839):** Increlex (mecasermin) approved for growth failure in children with severe primary IGF-1 deficiency. Orphan drug. Pediatric only.
4. **Orphanet:** Laron syndrome affects approximately 350-500 individuals worldwide. Prevalence: 1-9 per 1,000,000.
5. **AUA 2018 Guideline** (Mulhall JP et al., PMID: 29601923) and **Endocrine Society 2018** (Bhasin S et al., PMID: 29562364): Neither endorses routine AI use for estradiol management during TRT.

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