A Course Correction

I started this project to document a cyclical hormone protocol. That study is now closed, and what's left is going to look different. Here's what happened and why.

The short version

At my late-May gyno appointment, a culture came back positive for Group A Strep. I'm now finishing a course of Augmentin to clear it. That antibiotic is the whole story, because it does to a registered study exactly what it does to a microbiome: wipes out everything indiscriminately and leaves you somewhere you didn't plan to be.

A broad-spectrum antibiotic introduced partway through is an unplanned intervention that the original protocol never accounted for. It changes the conditions I was measuring, so the cyclical study as preregistered is no longer answering the question it set out to answer. Rather than pretend otherwise or quietly let it drift, I've formally closed out the original OSF preregistration with a termination note documenting the deviation.

To be clear: closed, not deleted. The Cycle 1 and Cycle 2 pharmacokinetic data stand on their own as a complete descriptive dataset. The reproducible trough, the paired serum anchors, the absorption picture across the cycle. None of that gets thrown away. It's truncated, not invalid, and it actually feeds directly into what comes next.

The slightly longer, more honest version

Somewhere along the way the original study became a kitchen sink. Hormone pharmacokinetics, microbiome dynamics, symptom tracking, tissue biology, all bolted onto a single N=1. Some of it produced genuinely interesting results. But the two main arms were quietly working against each other, and I didn't want to admit that for a while.

The cyclical hormone side undermined the microbiome side. The mechanism isn't mysterious. Establishing a Lactobacillus-dominant community in peritoneal neovaginal tissue depends on sustained local estrogen, which drives the glycogen the bacteria actually eat. My topical estrogen compliance was, charitably, bad. Without that steady signal the protective community never established, nothing produced colonization resistance, and an opportunist eventually walked through the open door. Getting a bacterial infection while running a study partly about preventing exactly that is not the result I wanted, but it is an extremely on-the-nose one.

So the infection is annoying, but it's also a clean off-ramp from a study that needed one.

What the project is now

One question, scoped tightly:

Can a peritoneal neovagina establish and sustain a Lactobacillus-majority microbiome under steady-state estrogen plus probiotic loading?

That's it. No cycling, no PK arm, no kitchen sink. The antibiotic that compromised the old study sets up the new one almost too well: it clears the board, both the little Lactobacillus that was there and the dysbiotic majority that wasn't doing me any favors, and gives me something close to a blank slate to build on.

I'll be honest that "blank slate" is an assumption rather than a measurement. Antibiotics disrupt, they don't sterilize, and a post-antibiotic environment has its own recolonization quirks. The real test also isn't whether I can spike Lactobacillus for a week. Probiotic loading can probably manage that. The question that matters is whether it holds once the loading stops. Establishing is easy. Sustaining is the whole ballgame.

A new, much more pointed preregistration for this is in the works. The protocol details (the probiotic schedule, the estrogen cream regimen, the sequencing timeline) are their own post, coming soon.

What this means for the blog

Fewer posts. The hormone-cycling project generated something to write about every few days: an injection, a trough, a serum draw, a symptom shift. A microbiome experiment is mostly waiting. You seed an environment, you leave it alone, and you sequence it weeks later. There isn't a daily readout, and pretending there is would just be filler.

So SecondCycle stays up, but the cadence slows down. Expect updates at the points where something actually changes: the new protocol, the antibiotic clearing, baseline, and whatever the sequencing says when the data finally comes back. Quality over quantity, partly by design and partly because the biology refuses to hurry.

More when there's more to say.