Hey guys, as the end of 2023 nears, I thought I'd do a post for those coming to this sub in desperate need of help.

In this post I’m going to be talking about the science of hair loss and what to do if you are balding and want to stop it.

I’m a medical student and have donated a lot of my personal time to pharmacology, hormones and hair protocols through research and experimentation. There’s a lot going on here on Reddit, and as a beginner it can be very daunting to decide on what to do. Obviously everything should be discussed with your doctor, but below is my best attempt at a guide to explain a little bit about hair loss:

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I first noticed I was balding around 12 months ago, and rather than get caught up in the genetics of hair loss and trying to figure out whether it was Dad, my Mum’s Dad, my Mum’s Dad’s Dad or the goldfish he owned when he was 10, I thought to myself:

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I can’t change my genetics. Whatever my DNA sequencing (genomic regions) has in store for me in regards to balding, that’s pretty much set. The best I can do is fight as long as I can using the highest quality science, products and methodologies to offset it.

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And that’s what I’ve been doing, with good success, over the past 12 months.

Let’s get into it, and I’m going to do this in order of most important to least (in my opinion).

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Getting to the root cause: DHT

Okay, so if we look at the entire testosterone/HPT axis pathway, cholesterol is converted to testosterone and some people think that’s the end of the line, but it’s actually not; 5-alpha reductase (5A1/2 in the image below) is the enzyme responsible for converting Testosterone (T) to its much more potent form DHT (dihydrotestosterone).

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Now, interestingly, 5-alpha reductase for whatever reason is very high prevalent in skin tissue - including the human scalp. And side note: this is why guys who take testosterone gel or cream often have very high levels of DHT compared to guys who take injections, because the cream is being converted through the skin into DHT at a much higher rate than injectable esters into muscle bellies. But, basically, it is this 5-alpha reductase activity in the scalp that is converting testosterone to DHT, and DHT through a variety of mechanisms leads to follicular miniaturisation (hair thinning, and eventual loss of your hair follicles).

But why? Well, there are hundreds of factors: hormonal (androgen receptor density & sensitivity to said androgens), physical, genetic, environmental. The list goes on.

Note; this study goes into a lot more depth for those of you interested.

But, how do we actually combat balding?

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Slowing Down Male Pattern Baldness

5-alpha Reductase Inhibitors (Finasteride, Dutasteride):

With how much I’ve spoken about 5-alpha reductase and DHT, it seems logical that stopping this conversion of Testosterone to DHT is the absolute first line of defence against hair loss.

To really, truly combat hair loss, the first mechanism is as follows: you absolutely need to reduce your hair follicles’ exposure to DHT.

And how do we do this? Well, finasteride is a drug that acts as a 5-alpha reductase inhibitor. Sold under the name Propecia, the molecule is a strong 5-alpha reductase inhibitor, and has been shown to inhibit around 70% of serum (blood) levels of DHT from peak. The usual starting dose is 1mg daily. Dutasteride (sold under the name Avodart) is an even more potent inhibitor (usual starting daily dose is 0.5mg), and can block up to 98% of conversion from T to DHT: it is a much more potent inhibitor of the enzyme that converts T to DHT. Dutasteride would be an option if you wanted a nuclear option to block almost all DHT. In fact, one of my favourite studies compared the difference between Finasteride vs. Dutasteride, and as you can see below, the suppression of DHT levels from Dutasteride was significantly more than Finasteride. Not only this, but the half life of Dutasteride is significantly longer than Finasteride (~8 hours vs. 5 weeks!), and you can see that in the Dutasteride group after stopping treatment (Follow-up Period), DHT levels remained suppressed for a much longer time.

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Side effects from 5-alpha reductase inhibitors are rare, although we should speak about them. Online, through various forums, Reddit posts, YouTube videos and TikTok’s time and time again I see posts about nasty Finasteride side effects, post-Finasteride syndrome and how Rob can’t get his Johnson hard anymore because of Finasteride, so his girlfriend left him.

Now, don’t get me wrong, side effects have been noted, although current research puts the risk of side effects at around 1-3% of people, so even though online there is a lot of noise about finasteride and its side effects, I personally don’t think the research supports this scaremongering. There is also going to be a natural selection bias with the stories online, because the guy for whom Finasteride is working well and who is not experiencing any side effects, he isn’t really going to post. Because why would he? He’s doing fine.

However, I absolutely sympathise with the people who just cannot tolerate 5-alpha reductase inhibitors. Side effects can be very real, and this is why it is vitally important to always consult with a qualified doctor before deciding on any medication: I’m just presenting the science. Everyone reacts slightly differently, and these can be strong medications - so it's important to be well-informed and sensible with whatever path you and your medical practitioner decide to go down.

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Topical Minoxidil 5% (Rogaine):

Minoxidil is a compound that has been shown to increase the rate of DNA synthesis in anagen (growth phase) bulbs of hair follicles. Basically minoxidil stimulates hair cells to move from telogen (resting phase) to anagen (growing phase) - so instead of having hair follicles resting, it is telling the body to move them back into a growth phase by shortening the resting phase. The idea here is that you get more ‘regrowth’ of hair follicles.

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Minoxidil stimulates hair cells to shorten the resting (telogen) phase and go back into an anagen (growing phase). Often, progress pictures will show significant new regrowth or ‘baby’ hairs growing with minoxidil treatment.

I apply Rogaine, a 5% strength Minoxidil foam twice daily in areas that I feel are receding. The nice thing about the foam is that it isn’t super sticky (unlike some people report with the gel), and it also acts as a nice way to hold my hair throughout the day, like hair product.

As you can see from the photo below, there is a vast difference between telogen (resting phase) and anagen (growing phase), and the idea is that the more hairs you can keep in anagen, the more healthy your hair will be, by limiting the amount of follicles that inevitably go through an anagen restart and die off.

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There is also the option of oral minoxidil, which anecdotally at least seems to be very powerful at regenerating ‘baby’ hairs (or, new regrowth). Again, oral minoxidil can have some pretty significant side effects and drug interactions with blood pressure medications, so speaking through with your doctor is key!

Ketoconazole Shampoo:

This shampoo is primarily an anti-dandruff shampoo, but research has shown it may increase the proportion of hairs in anagen phase (growth phase) - resulting in reduced hair shedding. This study showed that 1% ketoconazole shampoo increased hair diameter over baseline after 6 months of use and reduced shedding. Interestingly, participants’ hair diameter also increased over baseline, showing that it may play a role in creating thicker hair.

Nizoral is a common brand here in Australia of 2% strength ketoconazole shampoo.

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What is good about ketoconazole, is that it’s also a weak androgen receptor antagonist. What does this mean? It means it competes with DHT and Testosterone for binding to the active binding domain on the human AR (androgen receptor). If a compound can bind to a receptor without influencing its usual effects, it is said to be an antagonist. Basically, if ketoconazole can get into an androgen receptor before Testosterone or DHT, it will occupy that site and block T/DHT from binding and starting their usual process of killing off hair follicles (follicular miniaturisation).

Goodbye DHT, nobody wants you here.

Dermarolling

Derma-what?

Dermarolling is the process of creating micro punctures in the scalp skin to induce a wound healing response, with an array of tiny microneedles.

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In this study, the dermarolling + minoxidil treated group was statistically superior to the minoxidil only treated group in promoting hair growth in men with balding patterns, for all primary efficacy measures of hair growth. In fact, the microneedling group outperformed even the minoxidil group in terms of how much hair was regrown after 12 weeks:

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The mechanism seems to be that continued microtrauma to the scalp skin leads to a release of platelet derived growth factors and other growth factors that are sent to the area of scalp, to aid in the skin wound regeneration. The added benefit is that there seems to be some carry over effect to hair growth, as dermarolling seems to activate stem cells or ‘unspecialised’ cells that are yet to be differentiated, and differentiate them into hair follicle cells, meaning more hair growth. Basically, its a wound healing response that brings growth factors to the area of the scalp to increase hair growth.

I have played around with a few different protocols, but I use a 1.5mm roller and roll horizontally, vertically and diagonally for about 30 seconds in areas where my hairline is thinning or receding. I do this every 10 days. You don’t want to press so hard that you draw blood, but it should also hurt slightly. I mean, putting hundreds of tiny spikes into your scalp isn’t really my idea of Sunday night fun. But hey, if it regrows some hair why not?

There are also derma-stamps and motorised tools, all of which assist with the end goal: creating a wound healing response to bring growth factors to the scalp, and potentially assist the penetration of Minoxidil deeper into the scalp skin tissue.

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Natural DHT blocking compounds:

Natural DHT blockers are also options, although obviously the results aren’t going to be nearly as strong as what is mentioned above.

Some people have good results (anecdotally) with rosemary oil applied topically, green tea and saw palmetto are options here. However, the science is very hit and miss, and in any event, I can’t see natural compounds competing against the 'Big 4'.

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RU58841:

Now, that’s all good, but what if you need a nuclear chemical. Something that would attack the androgen receptor at a direct level in your scalp? Well, that compound is below. But a quick warning: I do not recommend this compound. A lot of people use it, but that doesn’t mean it’s safe. There is no (yes, zero) long-term safety data on the compound below, and whether you choose to take a completely untested chemical is up to you. But I don’t recommend it - have I said that enough?

Alright so, apart from sounding like a bunch of random letters because your cat ran over your keyboard, RU58841 is a strong DHT blocker (it has been shown to inhibit around 70% of DHT binding to the androgen receptor), but not in the way that Finasteride or Dutasteride work.

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Instead of finasteride and dutasteride which work on inhibiting the 5-alpha reductase enzyme, RU58841 works on the AR itself - occupying the active site, so that when DHT tries to get in and exert its hair destructive effects in the scalp, it can’t, it’s literally blocked from accessing the active site of the androgen receptor.

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And in this study, RU58841 was found to inhibit 70% of DHT binding. Combining something like finasteride or dutasteride which attacks 5-alpha reductase converting T to DHT with RU58841 which stops ~70% of DHT binding to the androgen receptor, and you’d now be attacking hair loss from 2 vectors: T to DHT conversion, as well as at a receptor level. Now you can start to understand why this is a nuclear option for hair loss, and incredibly powerful.

However, despite how good all of that sounds in practice, just remember, RU58841 is completely untested in regards to side effects. There is no long-term safety data on how it may or can impact human health, so what I’m saying (for legal reasons) is don’t use it. Get what I’m saying?

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Final Thoughts:

And, there it is guys. Now, just a quick note, this isn’t a super comprehensive list of all supplements for a hair regrowth/hair protection protocol, but is a solid start.

There are certainly more ‘niche’ options, or compounds in development now that may be promising (or not, looking at you Phase 3 of Pyrilutamide trials), but this guide was just the bare basics for a beginner to wrap his head around (no pun intended) the science and how to start combatting AGA.

In particular, if you want to save your hair, it’s going to be the ‘big 4’: finasteride (or Dutasteride), Minoxidil, Ketoconazole shampoo and derma-rolling roughly once a week to every 2 weeks.

This would follow the best possible science that we have at the moment, in terms of targeting as many vectors as possible:

1. T to DHT blockade (5-alpha reductase inhibitors, Fin/Dut)
2. Anagen/telogen manipulation (Minoxidil)
3. Localised scalp tissue androgen receptor antagonism (Keto, RU58841)
4. Wound healing response cascade (physical microneedling/trauma)

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Hope you enjoyed and got something out of this guide! My social links are on my profile if interested in more.

If the date in this post's title seems old, look for the newest thread here.

Use this thread for general questions and advice, “Am I balding?”, “What are my options?”, “Does anyone else experience this?”, as well as discussing side effects, treatment experiences, or looking for opinions on your hairline photos and treatment options.

Please don't rely on other users to diagnose conditions or guide your treatment decisions. While you can share personal experiences, what worked for you may not be safe or appropriate for someone else. If you're experiencing symptoms, concerned about side effects, or considering treatment, please talk to a doctor rather than relying on internet advice.

If you want useful feedback on your hair, post good photos: high resolution, multiple angles, good lighting, and ideally both wet and dry.

Mention what changes you’ve noticed and over what period of time. Some people naturally have thinner hair, a higher hairline, or less density, so context helps members give you better feedback. It's vital to take identical photos every few months. Remember that consistent lighting is important.

Age and family history are worth mentioning.

You might not get an answer if your question is too basic or common. Nobody can predict if a treatment will work for you.

This is a community, and you can help out fellow members by commenting under their photos and upvoting people that leave you comments.