TRT Clinic Revenue Loop
Your liver produces something called IGF-1, which is a hormone that drives tissue repair, muscle growth, and recovery. It does not produce IGF-1 on its own. It converts growth hormone into IGF-1, and that conversion depends on estrogen being present in sufficient amounts. That single dependency is the thing the revenue loop is built on.
Start with the full chain so you can see where the problem enters.
When you take testosterone, your body converts a portion of it into estrogen through a process called aromatization, which is just your body using an enzyme called aromatase to chemically transform testosterone into estradiol. This is not a side effect in the negative sense. This is normal physiology. Men are supposed to have estrogen. It plays a role in bone density, cardiovascular health, cognitive function, and as we just established, IGF-1 production.
When estrogen rises during TRT, some clinics respond by prescribing something called an aromatase inhibitor, or AI, which is a drug that blocks the aromatase enzyme and prevents that conversion from happening. The stated goal is to manage estrogen levels. The actual effect is that it drops estrogen dramatically, and when estrogen drops, the liver loses the signal it needs to efficiently convert growth hormone into IGF-1.
That is where the loop starts.
A 2017 randomized controlled trial by Dias and colleagues tested exactly this. They took 37 men aged 65 and older and split them into groups receiving either transdermal testosterone or an aromatase inhibitor. The testosterone group saw their IGF-1 rise by 15.3 nanograms per milliliter because the testosterone was aromatizing into estrogen and that estrogen was supporting liver conversion of growth hormone. The AI group saw an increase of 0.3 nanograms per milliliter. That is not a rounding error. That is essentially no change. The difference between those two numbers is the difference estrogen makes in this pathway.
So now you have a patient on TRT, their estrogen has been suppressed by an AI their clinic prescribed, and their IGF-1 has collapsed as a result. The clinic then identifies low IGF-1 and offers a solution.
The FDA-approved form of IGF-1 is called mecasermin, sold under the brand name Increlex. It was approved for a genetic condition called growth hormone insensitivity, sometimes referred to as Laron syndrome, which affects somewhere between 350 and 500 people worldwide. These are people whose bodies cannot convert growth hormone into IGF-1 at all due to a receptor defect. The drug exists for that population. It was not designed for, and is not approved for, a man on TRT whose estrogen was suppressed by a drug his clinic prescribed two months ago.
That distinction matters because it speaks to the risk profile. Mecasermin carries significant adverse effect risks including hypoglycemia, intracranial hypertension, and abnormal tissue growth precisely because IGF-1 is a potent anabolic signal. Using it in someone whose deficiency is iatrogenic, meaning caused by a medical intervention, rather than genetic is a very different clinical situation than the one it was designed for.
Now you might be thinking this is a niche problem affecting only the most aggressive TRT clinics, but a 2020 survey by Butaney and colleagues of nearly 500 physicians who were members of the International Society for Sexual Medicine found that 69.4 percent of them prescribed aromatase inhibitors for symptomatic elevated estrogen during TRT. Neither the Endocrine Society nor the American Urological Association currently recommends routine AI use for estradiol management during testosterone replacement therapy. That means the majority of physicians surveyed were prescribing outside of major guideline recommendations, and a large number of patients are sitting at the beginning of this cascade right now.
The reason estrogen management gets complicated is that elevated estrogen during TRT can produce real symptoms in some men, things like water retention, mood changes, and reduced libido, so the instinct to address it is not wrong. What is wrong is reaching for a drug that completely blocks estrogen production rather than adjusting the testosterone dose or delivery method to reduce how much aromatization is occurring in the first place. Dose and method adjustments address the root. An AI addresses the symptom while creating a downstream deficiency that then becomes a billable problem.
If you are currently on testosterone and an aromatase inhibitor, the most useful thing you can do is get your IGF-1 levels tested. A value that has drifted low since starting the AI is a signal worth paying attention to, and it is also a signal worth questioning before accepting a prescription that addresses it.
The deeper issue here is not that any one clinic made a bad decision. It is that the structure of this protocol, where a drug creates a deficiency and a second drug corrects that deficiency, can exist and persist without anyone in the chain being obviously malicious. A physician who genuinely does not understand the estrogen-to-IGF-1 pathway will still prescribe both drugs in good faith. The outcome for the patient is the same either way.
Understanding the mechanism is the only protection that actually transfers across every clinical encounter you will ever have, because once you know that estrogen drives IGF-1 production through hepatic conversion of growth hormone, no one can present you with the second prescription without you asking why the first one was necessary.
References
- **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.
- **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.
- **FDA Label (NDA 021839):** Increlex (mecasermin) approved for growth failure in children with severe primary IGF-1 deficiency. Orphan drug. Pediatric only.
- **Orphanet:** Laron syndrome affects approximately 350-500 individuals worldwide. Prevalence: 1-9 per 1,000,000.
- **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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