Email Archive

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.881 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z kinds of mechanisms peptide research is good at addressing. That’s not a coincidence. PCOS sits at the intersection of metabolic, inflammatory, and endocrine dysfunction. Any therapeutic class that targets those layers will eventually have something to say about PCOS. The fact that incretin peptides are already moving into mainstream PCOS care after

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.868 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z View this post on the web at https://derekpruski.substack.com/p/pcos-what-it-actually-is-how-its One of the most common conditions in women of reproductive age — and one that happens to sit at the intersection of every major mechanism peptide research targets. Research and educational purposes only. Nothing in this piece is medical advice. PCOS is a

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.867 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z 2025. Full text [ https://substack.com/redirect/43449217-f376-4861-a38e-9e1cbd27451b?j=eyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ] Kisspeptin improving ovarian insulin resistance (2026) Kisspeptin improves local ovarian insulin resistance in PCOS by modulating the PI3K/AKT/GLUT4 signaling pathway. PLOS One. 2026. Full text [ ht

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.862 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z Is Currently Managed This is the conventional medicine approach, based on the 2023 international evidence-based guideline. Knowing this matters because it’s the foundation that peptide research is being layered onto. Lifestyle modification. Always first-line, always non-negotiable. Diet (no single “best” diet — sustainable, individualized matters mo

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.857 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z clomiphene). For PCOS patients trying to conceive who don’t ovulate on their own, letrozole started day 3 of cycle, 2.5 mg titrated up to 7.5 mg as needed. Bariatric surgery. For PCOS patients with severe obesity who haven’t responded to other interventions. Often produces dramatic improvements in insulin resistance, androgens, and ovulation. What’s

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.856 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z These don’t address the underlying PCOS biology but may have relevance for the psychological burden. Tesofensine. Not a peptide, but worth flagging — it’s a triple monoamine reuptake inhibitor in development for obesity that’s showing strong weight loss data and may be relevant for PCOS patients who don’t tolerate GLP-1 agonists. The Honest Big Pict

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.845 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z accelerates fat breakdown for fuel. In a 2025 scoping review, the triple agonist class produced the largest improvements in weight loss and insulin sensitivity in PCOS-relevant research compared to GLP-1 and dual agonists. Retatrutide is still pre-FDA approval but is moving through trials. What the literature shows specifically for PCOS Significant

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.843 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z genetic risk, not just ovary-specific. Epigenetics and environment. The genetic background sets the stage, but environmental factors trigger the actual disorder. Prenatal exposure to elevated androgens, postnatal exposure to endocrine-disrupting chemicals (bisphenol A, certain pesticides, microplastics), poor diet, and sedentary lifestyle all alter

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.840 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z dysfunction in ovarian granulosa cells is one of the more recent additions to the PCOS pathophysiology picture, and it opens up a different category of peptide research. MOTS-c. A mitochondria-derived 16-amino acid peptide encoded by mitochondrial 12S rRNA. It improves insulin sensitivity, increases mitochondrial efficiency, and modulates metabolic

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching

Score 0.835 · Account tjphuhs@gmail.com · 5/12/2026, 12:13:59 PM

PCOS: What It Actually Is, How It’s Managed Now, And The Peptide Mechanisms Worth Watching from derekpruski@substack.com on 2026-05-12T16:13:59.000Z “BPC-157 treats PCOS” claim. It’s a “the upstream amplifier of inflammation in PCOS partially originates in the gut, and BPC-157 has research evidence for restoring gut barrier function” claim. KPV (lysine-proline-valine). A C-terminal tripeptide derived from alpha-MSH. Potent anti-inflammatory, immune-modulating, and antimicrobial activity, particu

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome)

Score 0.747 · Account tjphuhs@gmail.com · 5/12/2026, 9:13:06 PM

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome) from derekpruski@substack.com on 2026-05-13T01:13:06.000Z is regular. You see it as a long-term health condition with cardiovascular and metabolic implications, not just a fertility issue. What Didn’t Change The diagnosis itself stayed exactly the same. You still need two out of three of these: Irregular or absent ovulation High androgens (testosterone-type hormones) Polycystic ovaries on ultrasound, or elevated AMH (a hor

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome)

Score 0.740 · Account tjphuhs@gmail.com · 5/12/2026, 9:13:06 PM

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome) from derekpruski@substack.com on 2026-05-13T01:13:06.000Z means cycles become irregular or skip entirely. The trap: all four problems make each other worse Insulin resistance drives high testosterone. High testosterone makes insulin resistance worse. The scrambled brain signals push both of them further. The ovaries get caught in the middle. The ovaries aren’t broken. They’re responding exactly the way you’d expect them to

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome)

Score 0.739 · Account tjphuhs@gmail.com · 5/12/2026, 9:13:06 PM

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome) from derekpruski@substack.com on 2026-05-13T01:13:06.000Z View this post on the web at https://derekpruski.substack.com/p/pcos-has-a-new-name-meet-pmos-polyendocrine Everything below is for research and educational purposes only. Nothing here is medical advice. If this affects you personally, talk to a qualified clinician. The Update If you saw my earlier PCOS post — there’s a major update. As of May 12, 2026, PCOS has off

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome)

Score 0.731 · Account tjphuhs@gmail.com · 5/12/2026, 9:13:06 PM

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome) from derekpruski@substack.com on 2026-05-13T01:13:06.000Z About 1 in 8 women globally have this condition. That’s around 170 million people. And up to 70 percent of them are walking around undiagnosed — partly because the name made everyone think it was a niche ovary issue instead of a major whole-body metabolic problem. What’s Actually Happening This is the part most people never get explained clearly. Here’s the simple v

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome)

Score 0.726 · Account tjphuhs@gmail.com · 5/12/2026, 9:13:06 PM

PCOS Has A New Name: Meet PMOS (Polyendocrine Metabolic Ovarian Syndrome) from derekpruski@substack.com on 2026-05-13T01:13:06.000Z Guideline (Monash): Monash Centre for Health Research & Implementation — PCOS Guideline [ https://substack.com/redirect/9193435f-47f9-4a3a-b6d4-09e336327e38?j=eyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ] WHO PCOS Fact Sheet: World Health Organization — Polycystic Ovary Syndrome [ https://substack.com/redirect/0e65eafc-5cc8-46c9-821e-1ab6cb2b983e

Why Peptide Cycles Look Like a Slope, Not a Light Switch

Score 0.694 · Account tjphuhs@gmail.com · 3/29/2026, 9:14:23 PM

Why Peptide Cycles Look Like a Slope, Not a Light Switch from derekpruski@substack.com on 2026-03-30T01:14:23.000Z much. Or they stop a cycle, pull labs a week later, and think they’re already back to baseline. Neither snapshot tells the full story. Bloodwork reflects a system in motion, not a fixed point. Biomarkers — IGF-1, fasting insulin, lipids, hormones — shift gradually in response to peptide exposure, just like the effects themselves. It takes time for the body’s internal environment to

Zombie Cells vs. FOXO4-DRI

Score 0.691 · Account tjphuhs@gmail.com · 2/13/2026, 6:06:10 PM

Zombie Cells vs. FOXO4-DRI from huntershealthhacks@mail.beehiiv.com on 2026-02-13T23:06:10.000Z Happy Friday! I just released a brand new video breaking down FOXO4-DRI in detail. This is one of the most under-discussed peptides in the longevity space, yet it has some of the most interesting mechanistic data behind it. FOXO4-DRI | The Senolytic “Tune-Up” Peptide for Healthy Aging: (https://open.spotify.com/episode/5eW8CFOmZH7xN8ZxokV9I4?si=PP8ETsWATvWXvJUBAxWeQw) FOXO4-DRI falls into a class call

Fwd: The Future of Peptides, Longevity, and Human Performance

Score 0.691 · Account oc.tjphuhs@gmail.com · 3/20/2026, 10:03:01 PM

Fwd: The Future of Peptides, Longevity, and Human Performance from tjphuhs@gmail.com on 2026-03-21T02:03:01.000Z 10 to 15 years > • > KLP-1 (Klotho Protein Peptide 1), the new molecule Alex calls the closest thing to a "does everything" peptide. We're talking HRV improvement, fat loss, libido, skin quality, hair quality, recovery, and more > • > VD-11, a new peptide derived from salamander regeneration research that heightened Alex's senses so much he could smell his kid's diaper from a differen

Fwd: The Future of Peptides, Longevity, and Human Performance

Score 0.691 · Account tjphuhs@gmail.com · 3/20/2026, 10:03:01 PM

Fwd: The Future of Peptides, Longevity, and Human Performance from tjphuhs@gmail.com on 2026-03-21T02:03:01.000Z 10 to 15 years > • > KLP-1 (Klotho Protein Peptide 1), the new molecule Alex calls the closest thing to a "does everything" peptide. We're talking HRV improvement, fat loss, libido, skin quality, hair quality, recovery, and more > • > VD-11, a new peptide derived from salamander regeneration research that heightened Alex's senses so much he could smell his kid's diaper from a differen

Why Peptide Cycles Look Like a Slope, Not a Light Switch

Score 0.682 · Account tjphuhs@gmail.com · 3/29/2026, 9:14:23 PM

Why Peptide Cycles Look Like a Slope, Not a Light Switch from derekpruski@substack.com on 2026-03-30T01:14:23.000Z View this post on the web at https://derekpruski.substack.com/p/why-peptide-cycles-look-like-a-slope Most researchers picture peptide effects like flipping a switch. You dose, it works. You stop, it’s done. That mental model is going to set you up for frustration. The reality is much closer to a slow incline and a slow decline — a gradual ramp up, a peak somewhere in the middle, and

Mold Toxicity & Peptides: A Comprehensive Walkthrough

Score 0.680 · Account tjphuhs@gmail.com · 4/28/2026, 7:52:08 PM

Mold Toxicity & Peptides: A Comprehensive Walkthrough from derekpruski@substack.com on 2026-04-28T23:52:08.000Z works, but it’s downstream — you’re catching toxins after they’re already loose, hoping to clear them faster than they’re being released. It can take 5 to 8 years on this approach, and a lot of people stall out. The newer framework looks upstream — fix the immune system and mitochondria first, then detox. The logic: If your immune system is broken, it can’t recognize or clear what’s co

I Want to Rewrite the Narrative on SS-31 — Yes It’s an Energy Peptide, But That’s Not the Full Story

Score 0.675 · Account tjphuhs@gmail.com · 3/29/2026, 10:36:40 PM

I Want to Rewrite the Narrative on SS-31 — Yes It’s an Energy Peptide, But That’s Not the Full Story from derekpruski@substack.com on 2026-03-30T02:36:40.000Z damages the mitochondria further. It becomes a self-reinforcing cycle. What SS-31 Is Actually Doing SS-31 goes directly to that inner membrane and binds to cardiolipin. Think of it like a repair crew patching the walls of the power plant so electrons stop leaking out. When that leak is reduced: The production chain runs more efficiently Le

Mold Toxicity & Peptides: A Comprehensive Walkthrough

Score 0.675 · Account tjphuhs@gmail.com · 4/28/2026, 7:52:08 PM

Mold Toxicity & Peptides: A Comprehensive Walkthrough from derekpruski@substack.com on 2026-04-28T23:52:08.000Z Works This is where binders, sauna, glutathione support, and all the standard detox protocols suddenly start producing results in weeks instead of years. The immune system can recognize what to clear, the mitochondria have the energy to push toxins out of cells, and the barriers hold so you don’t re-absorb what you just excreted. This is also where addressing chronic infections fits —

GLP-1 Pregnancy Fears vs Reality… The First Real Data Is In

Score 0.675 · Account tjphuhs@gmail.com · 3/28/2026, 1:38:29 PM

GLP-1 Pregnancy Fears vs Reality… The First Real Data Is In from onthepen@substack.com on 2026-03-28T17:38:29.000Z expect at this stage. Rates of gestational diabetes, hypertensive disorders, preterm birth, and gestational weight gain were all over the place depending on the study, with no single direction that clearly stands out. Where this really lands for the OTP community is with Polycystic Ovary Syndrome, and this is not some small corner of the audience. This is a huge group of women who h

Why Peptide Cycles Look Like a Slope, Not a Light Switch

Score 0.674 · Account tjphuhs@gmail.com · 3/29/2026, 9:14:23 PM

Why Peptide Cycles Look Like a Slope, Not a Light Switch from derekpruski@substack.com on 2026-03-30T01:14:23.000Z compounds with extended half-lives Adjust slowly — changes take time to show up Don’t measure results at week one or two; measure at week four or five, after steady state has had a chance to establish Time bloodwork correctly — several weeks in, or several weeks after stopping — not immediately at either end When the cycle ends, treat the washout seriously — especially if doses were