[Unknown Member]

That’s not argumentative, but a fair question 🙂

I won’t claim to know everything, especially since I don’t have formal education in this field, but I do know a decent amount about health in general, and have been learning about it for years at this point. I would say that I know more than the average guy on steroids, for sure.

I’ve used things like pregnenolone and progesterone for years as well, and yes, I’m a guy. Occasional progesterone is very useful as a tool to relieve stress or excess catabolism. ( Dr. Ray Peat has some tremendous insight on this topic) Men make plenty of progesterone themselves and it’s not an exclusively female hormone. Many studies utilize progestins, so their conclusions are not always clear, since these progestins can often have estrogenic activity. Meaning, progesterone =/= progestins, and the studies need to be looked at carefully.

I also don’t see any harm behind androgen use as long as it is within physiological ranges. A few mg of DHT can very nicely inhibit cortisol and estrogen, and in fact boost pituitary output to the gonads. While TRT level doses of T are mostly fine, and that has been shown to be useful in plenty studies already. The main concern with androgens, as far as I can tell, is prostate enlargement and excess aromatization. Both of these can be watched and managed.

On the one hand, the argument could be made that I don’t know the real effects of long term hormonal manipulation. However, on the other, neither does anyone else who is exposed to the slew of environmental toxins which have hormonal actions as well. Take BPA, for example. It’s damn near unavoidable, and although it isn’t much of an issue acutely, it does provide a low grade estrogenic load over a long term. There are plenty of other “new” toxins which we are exposed to that we weren’t before. Many of them may be mild, but if you apply even a mild additional estrogenic load (that is, one that is exogenous) to a population, that means lower T levels for many men. This can become a problem for men who are in the lower end of the distribution. The results of lowered T are well known, and diseases such as T2D are more common.

This is obviously a complex topic, and my paragraph doesn’t touch even 1% of it, but I hope you get my point. Hormonal intervention may be dangerous, but so is not having optimized hormones. ( and other health aspects, such as diet, vitamin/minerals status, sleep, and microbiome). Plus, opportunity cost is real and is something everyone pays anytime their health isn’t optimized.

[Unknown Member]

Yes, I will be. Thank you!

[Unknown Member]

Yeah, you’re right. I didn’t know what to call it, so I put it in quotes.

Yes, everything I have is micronized, some better than others. It’s not an issue. And neither is solubility, since I’ve reached up to 21% of some hormones (DHEA, which is one of the more simple ones in terms of solubility).

Not sure what is so scary about potent actives as long as you have a clear understanding of what they are and what they do, but thank you for the warning.

[Unknown Member]

After thinking about it, I think I have three options.

1. Do what you and @chemicalmatt suggested. Get a more potent penetration enhancer, get a better emulsifier, and stick to that.

2. Attempt a micro-emulsion, since those seem to be highly effective in penetration as well.

3. Make a solution that isn’t an emulsion, and add some thickener to make it easier to use. Like you said, if nonanol is incorporating into the emulsification, then I need to not make an emulsion. Could I use carbomer for this?

[Unknown Member]

By saying, “lack of accessibility of creams intended for transdermal hormone delivery” I meant that, as a regular citizen, I can’t buy VersaBase. I’m sorry I didn’t make it more clear, I am a DIYer, not someone trying to sell a product. I hope that’s OK! @PhilGeis

My way of determining the effectiveness of a particular lotion is just to test it on myself. I have been messing around with various bio-active compounds for years, and generally have a good sense of things affect me. The lag time, required dose for the effect, and the duration of action all inform me of the effectiveness. If there would be a lab that could test something like this, it would be amazing, but for now it’s just subjective experience. That’s alright, though, since I am planning on personal use, therefore what works best for me, is the best formula (for me).

Damn, that’s fascinating but also disappointing. I will definitely be looking into other emulsifiers and the penetration enhancers that @chemicalmatt suggested. It would not be possible for me to realize this by myself, and your guys’ comments have been very helpful. Thanks!

If you have anything to add, I’m all ears.

[Unknown Member]

Reply to the last sentence:

I assume that I won’t be able to get 100% absorption regardless, right? Or are you saying that if I push the % higher, but don’t dramatically increase my solvents and penetration enhancers, then there would be too much hormone to be effectively pushed/pulled through?

And yes, they are quite expensive 🙂

[Unknown Member]

Well, I was planning on delivering all kinds of hormones, but they are all <5 logP. I mean, none are esterified, although I am really curious to experiment with that too. I read somewhere that if your penetration enhancement is strong enough and your drug is lipophilic enough, then your bottle neck is the aqueous layers of skin past the stratum corneum. In that case, using esterified hormones would be really interesting, since you could prolong the duration of action because of the esters, and also achieve high absorption (since your penetration is so good, assuming the enhancers don’t deplete).

Ok. I do have some reasoning behind my decision of PG/LA/and Nonanol. Take a look and let me know if I should switch to ethoxydiglycol or pentylene glycol. I’m not excited about using ethoxylated products, but the pentylene glycol does look interesting. I like PG because it’s carried to the liver and metabolized to lactic acid, which is harmless.

So there is a study showing impressive synergism between LA and PG. I’m not copying their ratios, and have additional ingredients would probably skew results. The largest difference is that they were testing esterified and fluoridated hormone analogues which are much larger and have high logP of 12.

Lauric Acid + PG study: https://sci-hub.st/https://link.springer.com/article/10.1023/A:1015314314796

Regardless, I used 1:1 of PG:LA mainly because it seemed to most efficiently solubilize the hormone at that ratio.( perhaps more PG is more effective, but too much screws with emulsification in my setup)

I know that both are decent enhancers on their own, so I’m hoping to achieve some synergism, but if not, it’s OK. I still need a fatty acid and some kind of alcohol for solubilization.

There is also this study which looks at fatty acids and their permeation enhancement of estradiol. LA is by far not the best, but I don’t like the idea of using MUFAS or PUFAS. I did try some oleic acid, but it went rancid too fast because of my carelessness. Even if I would have been really careful, it still came from the supplier already a tad rancid. Unless I can get a high quality supplier, I will stay away.

Fatty Acid Study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898574/

Some of the other fatty acids do look like better options, but I picked LA mainly because it was easily accessible, not too smelly, and not too long which might create excessive thickness.

Lastly, I picked nonanol because of two studies. The first one compared the medium chain fatty alcohols on melatonin absorption, and they all proved very effective. Nonanol was a good blend between low skin irritation and permeation enhancement. Now, that study used melatonin, but the second study compared various penetration enhancers on the uptake of estradiol, and undecanol proved very effective. The first study suggested that the medium chain fatty alcohols interfere with the cholesterol-cholesterol, and cholesterol-ceramide connections in the lipid matrix. If true, that means that nonanol would have a similar penetration enhancement as the undecanol. Both are roughly the same length as cholesterol (C9 vs C11), and both were a similar effectiveness in the melatonin study ( Decanol-C10 being the best).

Melatonin Study: https://sci-hub.ru/https://pubmed.ncbi.nlm.nih.gov/12429475/
Second study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823392/

This way, I have an alcohol, a fatty acid, and a fatty alcohol that can interfere with cholesterol. As far as I understand, alcohols and fatty acids mainly disrupt or extract other fatty acids or ceramides, while the cholesterol is more resistant.

Here are two of the tables from the fatty acids study.
Also, a graph of the Fatty Acid study, and the “Second Study”. The graph is exactly the same, I just remade it to make it less blurry and have better readability.

What do you think?

• This reply was modified 1 year, 1 month ago by  Unknown Member.

[Unknown Member]

Makes sense, but what happens to the hormone that PG solubilizes? Does it drag it out into the water phase? Because I’ve been messing around quite a bit, and the combination of fatty acid and PG are pretty effective in solubilizing the hormones. I’ve been adding it to the oil phase, and it can instantly make the oil phase go clear, solubilizing the hormone.

Ahhh! That makes a lot of sense, thanks for that pointer. I basically might be making salts (or just reducing them?) out of the salicylic acid and the sorbic acid, rendering them ineffective.

So what should I do about the emulsifiers? I need the lauric acid to be untouched, since its needed for penetration enhancement. Does it matter that I have a bit of the stearic salts? Some of the ingredients do prevent emulsification for a while, I think the nonanol and PG, but I do eventually get a decent emulsion that has been stable for around 3 ish weeks so far. Ideally, I would need roughly 6 months, after which It’s OK if it separates.

As a side question, I have been wondering if the creation of an emulsion is increasing the capacity of the lotion. A 10% hormone lotion’s oil phase will crash once it cools, and the hormone will cloud the solution, but once I form emulsions, there are no signs of crashing, grittiness or dryness. Is it possible that the hormone is incorporating into the micelle wall? Kind of like cholesterol in lipid membranes. Or, I guess it could be dragged out into the water phase with the PG? Sorry if this is too much questions, I’m awfully curious 🙂

Thanks for pointing that out too. I will keep an eye out for any skin reactions, and if anything, remove the limonene.

• This reply was modified 1 year, 1 month ago by  Unknown Member.

[Unknown Member]

Actually, no. I suppose I can call myself a biohacker? I’m primarily looking to do a sort of DIY TRT for a few months, but I am also interested in topical P4, P5, DHEA, and maybe 5a-DHP. I know I can get a simple script for TRT, but I really don’t like that idea. I’m not particularly scared of needles, but I think it’s an incredibly primitive method due to its invasiveness. Transdermal hormone delivery seems like a much more elegant solution in my opinion.

A large benefit of transdermal hormones and in particular T, is the reduced suppression and half life. With transdermal T, for example, you can achieve high blood levels for around a day but then bounce back in the next one or two days. Compared to the standard Test E which takes at least 2 weeks to completely flush out, transdermal T is much more attractive.

Obviously the other hormones are different when it comes to suppression, but for whatever reason, I am just really attracted to the idea of delivering hormones through the skin using a cream/lotion. For example, I was planning to also make a P5 or P4 cream for my mom once I figure out the best recipe.

That’s interesting. Could you tell me a bit more?