I've been on HRT for a decade, and my secondary puberty stalled out pretty early. Both my endo and I were doing everything "right" on paper—consistent injections, decent levels—but growth was minimal, and changing or rebalancing my hormones was at worst rollercoaster. I knew I was missing something fundamental.

For my experiment I went down the rabbit hole of nbe: genetic testing, hormone metabolite tests, and endless self-experimentation. I tracked everything—breast sensitivity, headaches, energy, hair shedding—and correlated it with my supplement protocol, injection timing, and even the type of tea I drank.

# Here's what I learned.

The Problem Wasn't Just My E2 Dose

For years, I thought I just needed more estrogen. I tried higher doses, even pseudo periods, but it didn't help. In many instances it made things worse. Headaches, bloating, mood swings, and completely stalled growth.

When I got my first Dutch test back, the picture became clearer:

· My estrogen metabolites were sky-high (especially 4-OH-E1, the toxic one).

· My methylation was extremely slow (2-Methoxy/2-OH ratio was 0.31, way below optimal).

· My progesterone metabolites were above the luteal range even on a moderate dose.

In plain terms: I was processing my hormones fast, but I couldn't clear the byproducts. My detox pathways were clogged.

The Genetics

I have a few key variants that explain what was going on:

· CYP3A4\\\*1B TT – I metabolize estradiol and progesterone quickly. Practically shredding it as soon as it entered my system.

· COMT AG – my catechol-O-methyltransferase enzyme is slow, so I can't clear estrogen metabolites efficiently.

· SLCO1B1 TT – my liver has reduced uptake of certain compounds, so some supplements and drugs linger.

· LOX CT – my collagen cross-linking is weaker, so I need extra copper and vitamin C.

Put simply: I'm a fast metabolizer with a slow clearance system and poor collagen deposition. It's a recipe for metabolite buildup, receptor desensitization, and nearly impossible growth.

The Experiment

I started my experiment with targeted detox support:

· DIM and sulforaphane to shift estrogen metabolism toward the safer 2-OH pathway.

· Calcium D-glucarate to support glucuronidation (Phase II detox).

· TMG, B2, methylfolate, methyl-B12, creatine to support methylation.

· Nettle tea on injection days + the day after to gently slow CYP3A4 and smooth the E2 curve.

· Copper, vitamin C, gotu kola, hyaluronic acid, hesperidin for collagen support.

As I tested and explored through my experimentation I added and removed supplements based on my biofeedback:

· No more EGCG – it's a potent COMT inhibitor and was worsening my metabolite backlog.

· No more saw palmetto, sea buckthorn, or NAC – they either interfere with my detox pathways or my SLCO1B1 genotype.

· Moderated protein and collagen intake – I used to take 100g protein + 30g collagen daily, but now I only take about 30g protein and 10g collagen on injection days and the day after, to provide resources for growth without overloading my system or feeling like I'm forcefully overeating.

The Breakthrough

After scaling up my detox support, I found that my "happy dose"—the dose that gave me stable, even-keeled levels before the experiment—was 3.5 mg per injection twice weekly. Now, with better detox with a lower dose (\\\~75–80%). Now 2.8–3.0 mg per injection keeps me within the growth window without the side effects I used to get at higher doses.

Things changed:

· Sensitivity became more consistent.

· Headaches reduced dramatically.

· Hair shedding slowed.

· I felt more even-keeled between injections.

I'm not 100% where I want to be—but I've had decent improvement from where I was, and a slow/steady path forward.

The Takeaway

It's not just about how much estrogen and progesterone you take/ have. It's about how your body processes them. For some, the body can handle it naturally. Sometimes a little HRT is enough. But sometimes—especially if you have genetic bottlenecks—you need extra help with supplementation and lifestyle tweaks.

If you're struggling with secondary puberty, stalled development or changes, I highly recommend looking into:

· Your metabolic bottlenecks (genetic testing can reveal these).

· Your detox cycle (Dutch test is gold for this).

· Targeted supplementation (don't just throw random things at it—match it to your genetics).

· Lifestyle tweaks (sleep, stress, diet).

It's a lot of work, but it's worth it. Listen to what your body is trying to tell you.

TL;DR: HRT dose alone isn't enough. You need to support your detox pathways, especially if you have genetic variants like slow COMT, fast CYP3A4, or SLCO1B1. My original happy dose was 3.5 mg per injection twice weekly; now with better detox I get that at 2.8–3.0 mg, staying in the growth window. I also moderated protein and collagen—now only 30g protein daily and 10g collagen on injection days + the day after, instead of 100g+30g daily. If you're stalled, look at your metabolic bottlenecks and detox cycle—not just your E2 level.

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Disclaimer: This is my personal experience and not medical advice. Always work with a qualified healthcare provider.

A year long experiment with nutrigenomics: HRT, Genetics, and Detox