CB-03-01 - When will it come to market? Will it be a stand alone treatment?

[whitegold]

Chemhead,

I am in the exact same situation as you. I recently came off of Fin after about 8 years of usage and have ordered some RU, hoping that with some Keto shampoo can help me maintain what hair the Fin helped me keep. I finally decided to come off the Fin because of not only the loss of libido, but I think it has actually shrank my package. I am a personal trainer and I too have had a hard time putting on or keeping any muscle mass while on the Fin. Hopefully the RU or maybe this CB will give us the same results as Fin, just without the horrible sides.

[Cookie]

Does CB-03-01 cream penetrate through the skin? If so, does it alter hormone and cause side effects?

[chemhead]

@Whitegold

Not to discourage you, but my experience with RU has not been positive. I stopped fin for a month completely to test RU on it's own and did not experience anything positive or negative.. basically nothing happened except that my hair thinned and since I returned to fin, I went through a shed (which is now just about over). That doesn't mean that RU is ineffective.. for me or anyone. I think my problem was delivery. I'm sure there are some people that absorb RU through the skin very effectively. I noticed often that after my hair was dry, I would feel the powder in my hair when running my hands through it.

Topical delivery is a complete turn-off for me because it simply doesn't work very well. I'm not done with RU, however. I'm currently designing and manufacturing a needle-less injection device to deliver pharmaceuticals and steroids like estradiol intradermally in 1000's of microliter-sized doses throughout the scalp. By doing this, I'll be able to decrease the amount of active pharmaceutical to have a positive effect and I'll also know what works and what doesn't without having to worry about whether or not it's actually getting to the target. It may end up taking up some of my time since I would have to self-administer so many doses, but if it works well enough, it may be a way for me to get away from oral fin and that alone would make it worth it. I also like the idea of injecting estradiol locally because I think it is the primary reason why fin stops my hair loss and significantly thickens my hair.

[chemhead]

@Cookie

None of us really have any idea how effective a CB cream would penetrate the skin. We do know, so far, that relatively little or no side effects occur from the use of CB and that it IS very effective.

I'm not sure about the fate of CB. One of the reasons why initial testing of CB was so effective is because they Cosmo used iontophoresis to drive CB into the scalp, which is very effective. I have used and still use an iontophoresis device and they definitely work.

I'm actually interested in why CB is so effective. Its structure is very similar to testosterone. The only difference is that at C17, testosterone has an alpha proton and a beta hydroxyl group, and CB has an alpha propionate and a beta carboxylic acid (ethanoic/acetic acid) group. CB more that likely gets reduced on C5 by 5AR to a DHT analogue that is ineffective because of the two above-mentioned substituents. Those two substituents hopefully increase the binding affinity of CB for the androgen receptor. Obviously with the lack of 5AR, CB is still an effective testosterone antagonist since it (hopefully) binds the AR with higher affinity.

[dan1938]

@Cookie

None of us really have any idea how effective a CB cream would penetrate the skin. We do know, so far, that relatively little or no side effects occur from the use of CB and that it IS very effective.

I'm not sure about the fate of CB. One of the reasons why initial testing of CB was so effective is because they Cosmo used iontophoresis to drive CB into the scalp, which is very effective. I have used and still use an iontophoresis device and they definitely work.

I'm actually interested in why CB is so effective. Its structure is very similar to testosterone. The only difference is that at C17, testosterone has an alpha proton and a beta hydroxyl group, and CB has an alpha propionate and a beta carboxylic acid (ethanoic/acetic acid) group. CB more that likely gets reduced on C5 by 5AR to a DHT analogue that is ineffective because of the two above-mentioned substituents. Those two substituents hopefully increase the binding affinity of CB for the androgen receptor. Obviously with the lack of 5AR, CB is still an effective testosterone antagonist since it (hopefully) binds the AR with higher affinity.

any updates on progress. I just started RU myself. By the way do you know if the RU concentrations are calculated by mass or volume. I did the calculations and by volume seem to make sense. However, with a density of 1.39, it seems like you need 75 mg/(ml of solvent) to achieve 5% conc, whereas in most posts people mention 50 mg /ml would give that concentration.

[chemhead]

I've long since quit RU (I stopped about a month after starting). I found that it had no effect at all. Based on what I now know, I'm not surprised it doesn't work. I actually happen to think that most pharmaceutical R&D companies are approaching hair loss from the wrong angle. In fact, I very strongly believe that hair loss is not in any way caused by androgenic hormones. Otherwise, I would have started losing hair when I turned 13~15 years. I do believe that DHT doesn't belong in the skin. It absolutely causes inflammation and redness, but I don't believe it causes hair loss.

Here's what I think is really happening: what is more significant is the high expression of 5 alpha reductase in skin and intrafollicularly. This is not because it causes the production of TOO MUCH DHT, it's because it acts as a "substrate sink" (testosterone being the primary metabolized substrate in skin and hair). So, in actuality, hair loss is not caused by an excess of androgenic hormone, but rather a lack of the other metabolites of testosterone and androstenedione (testosterone and androstenedione are in equilibrium with one another). Those metabolites lacking are estradiol and estrone from the aromatization of testosterone and androstenedione, respectively. Testosterone itself may even be responsible for the growth of hair.. not necessarily just its metabolites.

There is also a very specific reason why finasteride (or any 5 alpha reductase inhibitor) will only work temporarily... and only if it is dosed properly. Finasteride works because the inhibition of 5AR systemically causes a dramatic increase in the level of serum testosterone. This is why some people get gynecomastia. The elevated level of testosterone in all tissues where 5AR is expressed leaves more substrate to be aromatized. So, those with high expression of aromatase in breast tissue end up with gynecomastia. For the hair, though, this elevated level of testosterone in the skin and hair follicles is fantastic. Unfortunately, these levels do not remain elevated enough to have positive effects on hair for much more than a week. This is due to HPTA (hypothalamic-pituitary-testicular axis) feedback which signals the down-regulation of LH (luteinizing hormone) in response to high testosterone/estrogens. When you stop producing LH , testicular production and release of testosterone stops, resulting in the type of crash that anabolic steroid users can experience when coming off a cycle.

So, the only way that finasteride can really be effective (only temporarily) is by taking it at a very high dose. If you think of enzymes as being valves that regulate the flow of steroid/substrate from one steroid to another, the goal is to "shut off" the 5AR "valve" as quickly as possible (in a manner of speaking) so that you have higher levels of testosterone before your body realizes what's going on and shuts down LH. Once LH hormone shuts down, you crash, your junk shrinks, and you feel generally terrible.

[dan1938]

that is an interesting point,but Why does castration effectively halt hairloss. Almost all androgen synthesis is in the testicles, if testosterone and its metabolites were necessary for hair growth then, castration should have the reverse effect. From what I understand you are basically saying aromatization is good for hair but bad for the rest of your body? So then would topicals with aromatase or estrogen and its metabolites be a viable treatment? And could you please clarify what you mean by "substrate sink"?

[chemhead]

What I mean by "substrate sink" (assuming testosterone is our primary substrate which can be metabolized by 5AR, aromatase, etc.) is: think in terms of a heat sink for electronic components (processor, microprocessor, etc.). Just as a heat sinks draw away heat, a substrate sink is drawing away substrate. The presence of excessive 5AR draws away testosterone from other enzyme metabolism.

In the most basic sense, hair loss is a direct result of a lack of cellular energy. DHT and estrone have opposing effects on hair growth. DHT signals apoptosis by decreasing adenylate cyclase activity. Estrone does the exact opposite. So, it certainly does help to have less DHT, but having very low DHT doesn't guarantee that you still won't lose hair.

With regard to castration.. that's a complex issue. Castration will result in cessation of testicular testosterone (obviously), but that doesn't mean the body no longer produces testosterone. The adrenal gland is also able to effectively produce testosterone. While I'm sure castration could certainly cause cessation of hair loss, it wouldn't give someone, who would otherwise go completely bald, a full head of hair. Castration only helps in one regard with hair loss. The decrease in steroid overall means less DHT, but it also means less steroid... meaning the steroids you NEED to maintain normal cellular energy production are in deficit. The age of the castrate will also definitely be a factor in cessation of hair loss if expression of 5AR is related to pubertal increase in androgens. I don't think I've ever heard of a middle-aged castrate that grew back all hair in balding areas ... but then again, it's not something I've looked into.

I would definitely say that aromatization of testosterone/androstenedione is good for skin and hair and definitely, in excess, bad for every other tissue in the body. Estrogens are really growth hormones. An excess of estrogens unregulated by progesterone is exactly what can cause cancer.

One thing I know for certain is that testosterone absolutely DOES NOT cause hair loss. If this were true, you would see more bald 15 year olds.. a lot more. Hair loss starts when your body begins producing less testosterone. You can still have hair and high levels of DHT if you also have very high levels of testosterone, such as when in puberty. This is because you still have enough testosterone which can be metabolized to estradiol/estrone. In my own case, I had very red, itchy, and irritated skin (due to DHT) when I was a teenager. I also had very oily skin (due both to DHT and testosterone). As I grew closer toward the onset of hair loss, my skin became less oily and hair started falling out.

At present, I'm able to increase testosterone/androstenedione to supraphysiological levels, while simultaneously binding 5AR (with finasteride), and cause my skin to become much oilier and brigher and my hair extraordinarily thick.. thicker than when I was a teen. This is not a very safe thing to do, however, because the very high level of testosterone/androstenedione causes a significant increase in estrogens in other tissues.

[whatsgoingon]

What I mean by "substrate sink" (assuming testosterone is our primary substrate which can be metabolized by 5AR, aromatase, etc.) is: think in terms of a heat sink for electronic components (processor, microprocessor, etc.). Just as a heat sinks draw away heat, a substrate sink is drawing away substrate. The presence of excessive 5AR draws away testosterone from other enzyme metabolism.

In the most basic sense, hair loss is a direct result of a lack of cellular energy. DHT and estrone have opposing effects on hair growth. DHT signals apoptosis by decreasing adenylate cyclase activity. Estrone does the exact opposite. So, it certainly does help to have less DHT, but having very low DHT doesn't guarantee that you still won't lose hair.

With regard to castration.. that's a complex issue. Castration will result in cessation of testicular testosterone (obviously), but that doesn't mean the body no longer produces testosterone. The adrenal gland is also able to effectively produce testosterone. While I'm sure castration could certainly cause cessation of hair loss, it wouldn't give someone, who would otherwise go completely bald, a full head of hair. Castration only helps in one regard with hair loss. The decrease in steroid overall means less DHT, but it also means less steroid... meaning the steroids you NEED to maintain normal cellular energy production are in deficit. The age of the castrate will also definitely be a factor in cessation of hair loss if expression of 5AR is related to pubertal increase in androgens. I don't think I've ever heard of a middle-aged castrate that grew back all hair in balding areas ... but then again, it's not something I've looked into.

I would definitely say that aromatization of testosterone/androstenedione is good for skin and hair and definitely, in excess, bad for every other tissue in the body. Estrogens are really growth hormones. An excess of estrogens unregulated by progesterone is exactly what can cause cancer.

One thing I know for certain is that testosterone absolutely DOES NOT cause hair loss. If this were true, you would see more bald 15 year olds.. a lot more. Hair loss starts when your body begins producing less testosterone. You can still have hair and high levels of DHT if you also have very high levels of testosterone, such as when in puberty. This is because you still have enough testosterone which can be metabolized to estradiol/estrone. In my own case, I had very red, itchy, and irritated skin (due to DHT) when I was a teenager. I also had very oily skin (due both to DHT and testosterone). As I grew closer toward the onset of hair loss, my skin became less oily and hair started falling out.

At present, I'm able to increase testosterone/androstenedione to supraphysiological levels, while simultaneously binding 5AR (with finasteride), and cause my skin to become much oilier and brigher and my hair extraordinarily thick.. thicker than when I was a teen. This is not a very safe thing to do, however, because the very high level of testosterone/androstenedione causes a significant increase in estrogens in other tissues.

Either I just learned a whole lot about a plausible theory or I'm too tired to read through it clearly. But seriously, really cool read on your 4 posts. Interesting subjects were mentioned and explained well. Nice concentration of thoughts.

You mentioned you stopped your hairloss? Or was that hypothetical? And if you did, how? (might of skimmed through it ) Curious is all.

[burtandernie]

The reason though 15 year olds dont go bald is because something happens with how your hair reacts to the androgens you have as you get older and have genes,hair susceptible to it. Whether its something with receptor changes or probably something much more complex and that big piece is not figured out yet. Androgens do cause MPB and if you believe DHT binds to receptors then its hard to imagine T and other male androgens do not also behave the same way just being much weaker androgens.
Castration stopping MPB is probably the only evidence we have at all so far showing MPB can be completely prevented. Key word being castration prevents MPB if timed properly. It does not regrow hair or possibly even save hair already under the process.

[dan1938]

nicely explained. I will try to pull up studies that might support and refute your theory, but how are you able to increase your testosterone/androstenedione levels? And how would you be able to sustain it knowing that the hypothalamic–pituitary–gonadal axis will try to get you back to homeostasis?
what kind of effect would supraphysiological levels have on your kidneys and liver?

[whatsgoingon]

Castration stopping MPB is probably the only evidence we have at all so far showing MPB can be completely prevented. Key word being castration prevents MPB if timed properly. It does not regrow hair or possibly even save hair already under the process.

Not sure there are enough studies to back up post-puberty castration doing nothing.

But I guess you could take a census from testicular cancer patients and transgender who have their parts removed.

But I do believe it would stop the loss just from a rule of thumb. Regrow back to NW1, doubtful. But I think even tracy mentioned that her transsexual friends could only get back to a NW2. But that's anecdotal.

Wasn't taking a jab at you, just adding a bit of input.

[inbrugge]

What I mean by "substrate sink" (assuming testosterone is our primary substrate which can be metabolized by 5AR, aromatase, etc.) is: think in terms of a heat sink for electronic components (processor, microprocessor, etc.). Just as a heat sinks draw away heat, a substrate sink is drawing away substrate. The presence of excessive 5AR draws away testosterone from other enzyme metabolism.

In the most basic sense, hair loss is a direct result of a lack of cellular energy. DHT and estrone have opposing effects on hair growth. DHT signals apoptosis by decreasing adenylate cyclase activity. Estrone does the exact opposite. So, it certainly does help to have less DHT, but having very low DHT doesn't guarantee that you still won't lose hair.

With regard to castration.. that's a complex issue. Castration will result in cessation of testicular testosterone (obviously), but that doesn't mean the body no longer produces testosterone. The adrenal gland is also able to effectively produce testosterone. While I'm sure castration could certainly cause cessation of hair loss, it wouldn't give someone, who would otherwise go completely bald, a full head of hair. Castration only helps in one regard with hair loss. The decrease in steroid overall means less DHT, but it also means less steroid... meaning the steroids you NEED to maintain normal cellular energy production are in deficit. The age of the castrate will also definitely be a factor in cessation of hair loss if expression of 5AR is related to pubertal increase in androgens. I don't think I've ever heard of a middle-aged castrate that grew back all hair in balding areas ... but then again, it's not something I've looked into.

I would definitely say that aromatization of testosterone/androstenedione is good for skin and hair and definitely, in excess, bad for every other tissue in the body. Estrogens are really growth hormones. An excess of estrogens unregulated by progesterone is exactly what can cause cancer.

One thing I know for certain is that testosterone absolutely DOES NOT cause hair loss. If this were true, you would see more bald 15 year olds.. a lot more. Hair loss starts when your body begins producing less testosterone. You can still have hair and high levels of DHT if you also have very high levels of testosterone, such as when in puberty. This is because you still have enough testosterone which can be metabolized to estradiol/estrone. In my own case, I had very red, itchy, and irritated skin (due to DHT) when I was a teenager. I also had very oily skin (due both to DHT and testosterone). As I grew closer toward the onset of hair loss, my skin became less oily and hair started falling out.

At present, I'm able to increase testosterone/androstenedione to supraphysiological levels, while simultaneously binding 5AR (with finasteride), and cause my skin to become much oilier and brigher and my hair extraordinarily thick.. thicker than when I was a teen. This is not a very safe thing to do, however, because the very high level of testosterone/androstenedione causes a significant increase in estrogens in other tissues.

I just wanted to say great posts chemhead. I tried to soak it all in and it's a bit overwhelming, but you have some real interesting theories there.

However, you didn't mention about the CB treatmen in respect to your hypotheses. You mentioned Fin would be succesful only temporary, but I'm interested to see your thoughts about the different treatments, mainly CB, beyond just Fin.

Thanks.

[akai]

I won't believe any of these drugs or procedures with a lot of promise are going to come out until they come out. It's pretty depressing when you see decade old posts of people who bought into the hype of a medication or procedure that was ineffective or never made it to market.

[dan1938]

I won't believe any of these drugs or procedures with a lot of promise are going to come out until they come out. It's pretty depressing when you see decade old posts of people who bought into the hype of a medication or procedure that was ineffective or never made it to market.

you have to understand that a treatment may not be commercialized for reasons other than its efficacy. one reason that comes to mind is profitability. If a company doesn't believe that a product will make them any money, why would they spend millions patenting it?so the only choice we have until they come out with something is to take matters in to our own hands. Humans were using herbs and plants in their surroundings for millions of years for different ailments. Some were effective, some weren't. The only thing the pharmaceutical companies are doing is manipulating what is found in nature to work for us. For example, there are many naturally found oils/foods that have anti androgenic, anti-aromatase, anti-estrogenic, etc properties. They were being used well before Finasteride, Letro, nolva, etc came in to our lives.