u/noeyys

When looking at some of the supposed activated follicular units, it’s noticeable that some of the units were already activated at baseline (before PP405 was introduced) in the human subjects. This makes me question why Pelage circled those follicular units in the first place. Did they inflate the efficacy? Or did they have no idea what they were looking at in some areas?

In any case, seems like bad news. I remember looking at the biopsies and this was an issue there too.

82 days since the dermatologist conference and still no hair count numbers for treatment and placebo groups.

The fungus strongly linked to seborrheic dermatitis, Malassezia, can create a feedback loop on the scalp when there is chronic overgrowth. Malassezia releases lipolytic enzymes that break down scalp sebum into free fatty acids and glycerol. It uses some of those lipids to survive, but the issue is not just that Malassezia “eats oil.” The bigger issue is that this process changes the scalp environment itself.

Those lipid breakdown products can irritate the skin barrier, trigger inflammation, increase flaking, and potentially push the scalp into a more oil-producing, fungus-friendly state. Over time, the scalp can become oilier, itchier, flakier, and more favorable to the same organisms driving the problem.

According to Cheng et al. in their 2025 review, “Research Progress on the Exacerbation of Lipid Metabolism by Malassezia and Its Impact on the Skin Barrier Function,” Malassezia depends on host sebum because it cannot make certain fatty acids on its own. The review specifically describes a “sebum overload–fungal proliferation” feedback loop, where Malassezia-derived free fatty acids may stimulate sebaceous glands to produce more sebum, which then gives Malassezia more substrate to grow on.

That does not mean Malassezia is always the original reason someone has oily skin. DHT, genetics, hormones, diet, stress, product buildup, hair density, and scalp inflammation can all contribute. But once Malassezia overgrowth is established, it may help maintain and worsen the oily/inflammatory cycle.

This is where DHT itch and AGA come in. I do not think DHT itch necessarily means DHT directly activates an itch nerve. It may be more accurate to think of it as an androgen-sensitive scalp environment becoming more sebaceous, lipid-rich, and microbially imbalanced. That environment can become more favorable to organisms like Malassezia and Cutibacterium, which metabolize lipids, produce inflammatory byproducts, alter pH, and interact with other microbes.

According to Suzuki et al. in the 2021 paper “Scalp Microbiome and Sebum Composition in Japanese Male Individuals with and without Androgenetic Alopecia,” men with AGA had higher scalp triglyceride and palmitic acid content, more Malassezia restricta, increased Cutibacterium, and decreased Corynebacterium. That matters because it suggests balding scalps may not only have miniaturizing follicles. They may also have a different oil and microbiome profile.

Diet fits into this too, but not in a simplistic “just eat clean bro” way. According to Lim et al. in the 2019 paper “Dietary Patterns Associated with Sebum Content, Skin Hydration and pH, and Their Sex-Dependent Differences in Healthy Korean Adults,” a dietary pattern low in beans and high in meats, dairy products, beverages, and alcohol was associated with higher sebum content and less acidic skin pH. The authors also discuss how high-glycemic diets and milk products may influence insulin and IGF-1 signaling, which can stimulate sebaceous gland activity.

How to Fix it:

1. Treat seb derm like a chronic condition

Medicated shampoos can help, but I do not think people should always rely on only one shampoo forever. Some people do better rotating different antifungal or anti-dandruff agents instead of hammering the same one nonstop.

A simple rotation could look like:

* Week 1: ketoconazole shampoo

* Week 2: ciclopirox shampoo

* Week 3: zinc pyrithione shampoo

Then repeat.

I personally like ciclopirox because it can be less drying than ketoconazole for some people while still having antifungal and anti-inflammatory properties. Selenium sulfide is another option.

Terbinafine shampoo may also be worth looking into. It has been shown to help especially in the oral terbinafine case where it is usually what is used for true scalp fungal infections like tinea capitis. Shampoo or cream of Terb is best though (using oral long term is bad for gut health).

The point is not to destroy the scalp barrier. The point is to reduce Malassezia pressure without making the scalp raw, dry, and more inflamed.

2. Be careful with alcohol-based scalp antiseptics

A 70% ethanol and 30% water solution can weaken microbes on the skin, but I would be careful. Ethanol can be drying and irritating, especially on an already inflamed scalp. If someone uses it, I would not treat it like a daily long-term scalp routine. It should be used cautiously, away from open wounds, and ideally discussed with a dermatologist if the scalp is already irritated.

For many people, a better starting point is medicated shampoo, benzoyl peroxide wash if folliculitis is present, and avoiding heavy oils/product buildup. However, ethanol can help if your barrier is fine and you're using 50-70% with q.s water. This should help reduce the overgrown microbial colonies.

3. Consider C6/C8 MCT oil, not random heavy oils

Applying more “oil” sounds like a paradox, but not all oils behave the same way.

Malassezia tends to do better with certain longer-chain fatty acids and oil-rich environments. But C6/C8 MCT oil is different. C6 is caproic acid and C8 is caprylic acid. These shorter-chain lipids are harder for Malassezia to use the same way it uses longer-chain oils, and some studies suggest medium-chain triglycerides or medium-chain fatty acids can be antimicrobial against Malassezia.

So, instead of using coconut oil, castor oil, olive oil, butters, or greasy pomades on a seb derm-prone scalp, I would look more toward C6/C8 MCT oil or squalane as safer oil-like options.

A practical approach could be applying a small amount of C6/C8 MCT oil a few times per week and seeing how the scalp responds. Do not overdo it. If it makes the scalp worse, stop.

4. Low-dose isotretinoin may be underrated for severe oily scalp

This is not a casual recommendation, but it is worth discussing.

For people with severe oily scalp where the scalp gets greasy again within hours, very low-dose isotretinoin may be one of the more underrated options. The idea is simple: if sebum is feeding the cycle, reducing sebum output can change the entire scalp environment.

An older study by Geissler, Michelsen, and Plewig titled “Very low dose isotretinoin is effective in controlling seborrhea” looked at very low doses such as 2.5 mg daily, 5 mg daily, and 2.5 mg three times weekly. The study found improvements in oily skin and oily scalp hair, along with reductions in sebum output, follicular filaments, microcomedones, sebaceous gland size, and Propionibacterium acnes, now called Cutibacterium acnes.

These days, when people talk about “low-dose isotretinoin,” they may mean different things. Standard acne dosing is much higher, often around 0.5 to 1 mg/kg/day. But for oil control or seborrhea, some dermatologists use much lower doses like 2.5 mg, 5 mg, 8 mg, or 10 mg depending on the person and the goal.

However, isotretinoin is serious. It is teratogenic, meaning it can cause severe birth defects. In the United States, it is controlled through iPLEDGE. Anyone who can become pregnant has to follow strict pregnancy prevention and testing rules. It can also cause dryness, lipid changes, liver enzyme changes, mood-related concerns in some people, and temporary hair shedding.

That last point matters for people with hair loss. Higher-dose or prolonged isotretinoin has been associated with temporary shedding in some patients. There is also a mechanistic paper by Foitzik et al. showing that all-trans retinoic acid can push isolated human scalp hair follicles toward premature catagen, meaning the regression phase of the hair cycle. So I would not use isotretinoin casually on a shedding-prone scalp. Lowest effective dose, clinician supervision, and monitoring matter.

5. Fix the diet side without pretending diet cures everything

Diet can matter because sebum is hormonally and metabolically influenced.

I would focus on:

* reducing high-glycemic foods

* reducing sugary drinks

* reducing frequent processed carbs

* reducing alcohol

* testing whether dairy worsens oiliness, acne, or itch

* increasing fiber

* eating more beans, vegetables, fruits, and whole foods

* getting omega-3-rich foods

* adding fermented foods if tolerated

The gut-skin axis is real, but it is complex. Fermented foods, fiber, and less ultra-processed food may help regulate the gut microbiome and reduce systemic inflammatory pressure. But oily scalp is not always just a diet issue. For some people, DHT, genetics, scalp microbiome changes, product buildup, stress, sweating, and inflammatory skin disease are all part of the picture.

6. Dutasteride may help if DHT is part of the oil/itch loop

Dutasteride lowers scalp DHT more strongly than finasteride and may help some people whose oily scalp or “DHT itch” is driven by androgen activity. It is not an antifungal, so I would not expect it to replace seb derm treatment. But if DHT is upstream of the oily scalp environment, lowering DHT may help reduce one of the drivers of the loop.

So the goal is to break the loop from multiple angles:

* control Malassezia

* avoid heavy oils that feed the wrong environment

* use C6/C8 MCT oil or squalane if an oil-like vehicle is needed

* treat folliculitis if bumps are present

* reduce diet-driven sebum triggers

* manage DHT if relevant

* consider low-dose isotretinoin only for severe cases under medical supervision

I paid for a third-party in vivo skin absorption / transdermal delivery evaluation for a 10% min sulfate emulsion, using confocal Raman spectroscopy rather than a basic ex vivo Franz diffusion cell model.

The goal was to answer a more fundamental formulation question: does liposomal min sulfate move past the outer skin barrier after topical application, and can a minoxidil sulfate signal be detected inside the skin over time?

The study used an RZ660 In Vivo Raman Analyzer to scan human skin after a single topical application. According to the report, the test involved 3 valid subjects, all women aged 28–37.

The test measured at multiple time points:

T0h: baseline, before application
T1h: 1 hour after application
T2h: 2 hours after application
T4h: 4 hours after application

The product was applied at about 4.0 ± 0.1 mg/cm² to marked test areas. The Raman system then measured the minoxidil sulfate-associated signal at different skin depths.

The data support that liposomal minoxidil sulfate does pass the outer layer of skin and produces a measurable, time-dependent min sulfate signal inside human skin.

The main result was that the signal increased and moved deeper over time:

1 hour: detectable signal to around 12 µm
2 hours: detectable signal to around 27 µm
4 hours: detectable signal to around 36 µm, with no signal detected beyond roughly 39 µm

The cumulative penetration content also increased over time:

1 hour: 24.934 µg/cm²
2 hours: 55.854 µg/cm²
4 hours: 68.944 µg/cm²

The 36–39 µm number is not the maximum possible depth it can ever reach. It is the endpoint of detectable signal under this specific study design and four-hour testing window. The purpose was to see whether absorption occurred, whether it progressed over time, whether the formulation crossed the outer barrier, and whether any immediate issues appeared during observation.

Again, this is (to my knowledge) the first study ever conducted using liposomal min sulfate and Raman spectroscopy technology on humans.

Rapid weight loss leads to rapid release of free fatty acids as you break down fat. The hair follicles, being encased in adipose tissue, experiences this surge in fatty acid production which has been shown to destabilize the hair growth cycle causing hair follicles to switch to catagen earlier than they otherwise would - which could cause Telogen effluvium months after the trigger.

This shed seems to happen when you lose 10-15% of your baseline body weight within 2-3 months. However people who have less protein in their diet are more exposed to this kind of hair fall.

Some diets decline IGF-1 levels which also impact hair growth signals too.

So a rate of weight loss at 0.5-1.2 lbs per week should be considered a safe zone according to what the literature shows along with consuming a moderate amount of protein.

GLP-1 studies are essentially mirroring what crash diets do so we’re getting a lot of insights from them especially when it comes to hair fall.

https://en.kintor.com.cn/news_details/1803365125008502784.html
GT20029 has a real chance of replacing finasteride for many people if larger trials confirm the early data.

Unlike finasteride or dutasteride, it does not lower DHT systemically. It is a topical PROTAC designed to bind the androgen receptor, recruit an E3 ubiquitin ligase, and send that receptor to the proteasome for degradation. So instead of just lowering DHT, the goal is to reduce the receptor DHT uses inside the follicle environment.

This could make it a serious option for people who cannot tolerate finasteride, are worried about systemic hormone changes, or want a more targeted topical approach. And obviously it’s stackable with fin and dut.

https://en.kintor.com.cn/news_details/1803365151294205952.html
https://en.kintor.com.cn/news_details/1803365146143600640.html
The safety data is also promising. In both the China and U.S. Phase 1 studies, systemic exposure was extremely low, even after repeated dosing. That matters because the entire appeal of GT20029 is local scalp activity without meaningful systemic exposure. China phase 2 also showed low to zero systemic exposure.

https://pubmed.ncbi.nlm.nih.gov/41328006/

Where it comes to results, The China Phase 2 AGA data is promising.

The study tested 180 Chinese men across six groups: 0.5% once daily, 1.0% once daily, once-daily placebo, 0.5% twice weekly, 1.0% twice weekly, and twice-weekly placebo.

All GT20029 groups improved hair counts, but only 0.5% once daily and 1.0% twice weekly clearly beat their matching placebo groups. The 1.0% twice-weekly arm also improved hair width.

Now this could seem odd because you would expect 1.0% once daily to clearly outperform 0.5% once daily, but it did not. Instead, 1.0% twice weekly looked like one of the stronger arms. However the 1.0% once daily had started at a lower baseline hair count in the group than its placebo so perhaps that group has more severe AGA subjects which made GT underperform (especially with how small the groups are).

The mechanism of GT has a lot of promise. If larger and longer trials keep showing low systemic exposure and meaningful hair growth, then yes, I think it probably replaces finasteride for many people. It could also be stacked with finasteride or dutasteride because lowering DHT and degrading the androgen receptor are not the same mechanism.

https://pubmed.ncbi.nlm.nih.gov/39884271/
https://www.nature.com/articles/s41467-026-70153-4
Now, there is the recent GPR133 paper that’s making people think that outside of lowering scalp dht, there’s nothing effective enough to help slow or reverse hair loss like fin and dut.

In this paper, the authors suggest DHT can activate GPR133 in the connective tissue sheath, causing sheath contraction, Piezo-type mechanosensitive ion channel component 1 activation, progenitor-cell stress, and reduced follicle growth. So in other words, DHT doesn’t need the Androgen Receptor to cause stress to the hair follicle. It may restrict its growth via GPR133 receptor. So this could mean drugs like GT are useless.

https://www.nature.com/articles/s41467-026-70153-4
However I have an issue with the paper as there are some inconsistencies that make me write off GPR being a major issue for Aga. Much of the work in the paper comes from isolated follicles, ex vivo systems, single-cell/spatial transcriptomics, and humanized mouse models. These are useful tools, but they do not prove that GPR133 inhibition restores AGA in a normal human scalp environment.

https://www.nature.com/articles/s41467-026-70153-4
The biggest issue is the dermal papilla data. The authors found that dermal papilla subcluster percentage and distribution were mostly comparable between healthy, non-balding, and balding follicles. That is strange because the dermal papilla is supposed to be one of the main structures disrupted in androgenetic alopecia. They typically reduce in number and size.

https://www.nature.com/articles/s41467-026-70153-4
https://pubmed.ncbi.nlm.nih.gov/35033537/
Even the authors acknowledge the issue. They note that AGA is usually understood through dermal papilla miniaturization, reduced dermal papilla volume, reduced cell number, and loss of inductive capacity. They also cite their own prior work showing androgen receptor upregulation in dermal papilla cells, reduction in size and density of these cells along with their signaling activity, and more comparable to their recent study they do note vascular regression around the dermal papilla. They admit their newer single-cell analysis did not show obvious dermal papilla changes beyond reduced angiogenesis signaling and that’s a major issue and contradiction of the literature and pathway of AGA.

https://pubmed.ncbi.nlm.nih.gov/35033537/
That is not a small detail. if the newer GPR133 paper finds balding and non-balding dermal papilla subclusters looking mostly similar, that discrepancy needs to be explained before we oversell the significance of GPR133 and DHT on the hair follicle.

https://www.nature.com/articles/s41467-026-70153-4
To me, this suggests the GPR133 paper is capturing one slice of AGA biology, not the whole disease. The study focused heavily on early miniaturizing anagen follicles from the frontal hairline edge, with a limited number of male samples. That is useful mechanistic data, but not enough to claim this pathway explains AGA broadly across the whole scalp.

That is why GT20029 still makes sense. If androgen receptor activity in the dermal papilla region is one of the main upstream problems, then locally degrading the androgen receptor remains a direct strategy. GPR133 may add another layer to DHT biology, but it does not replace the classic androgen receptor/dermal papilla pathway.

When looking at Reddit, a lot of the shedding reports came in days into creatine use. Typically the hairs you shed now were already set to shed 3 months before as they had formerly ended their catagen. So there’s no way creatine would cause people to shed like this. People are just concerned over nothing and hyper fixated on normal shedding patterns.

Take creatine or not. But it’s clear that some people are fixated on shedding.