S
samskeyti
Iron
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What i'm going to write is purely theoretical. I haven't experimented with this entire regimen, however, from a theoretical standpoint, this stack of medications should pinpointly address both androgenetic alopecia and prevent any possible sexual dysfunction and mental&cognitive problem due to 5ar-reductase inhibition.
We all already know the basics of AGA, but I have to begin from scratch to build up to the point I want to make. DHT is the main culprit in AGA. All the other "blood flow" or "calcification" theories of AGA are either psuedo-scientific or just very negligible factors as long as DHT is addressed. They don't make sense on their own. It's the scalp dht that binds to androgen receptors in the hair follicles which causes miniaturization and therefore hair loss, serum dht and dht in other tissues are irrelevant. However, there is no way to effectively lower scalp dht levels without lowering the serum and local production of dht in other 5ar dense tissues, such as skin, prostate and penis. DHT is a paracrine hormone, which means that serum and local concentrations of DHT don't equally correspond. Topical finasteride goes systemic, it's been shown by numerous studies. Topical dutasteride would go systemic as well but the situation is even worse for it since due to the molecular weight of dutasteride, whether it penetrates the scalp skin effectively and works is still a debate topic. So, with the currently available set of drugs, we have to use an oral 5ar inhibitor. Now, you may ask; "What about RU58841?" RU58841 has indeed negligible systemic absorption which does not lead to any physiological effects when used at proper doses (50-75 mg per day). However, from what I've seen in the user anecdotes, RU58841 as a standalone monotherapy fails to treat AGA %99 of the time. There are two reasons for this: 1. RU58841 has %5 of the binding affinity of DHT to androgen receptor, which means DHT's binding affinity is 20 times higher than that of RU58841. 2. Unlike testosterone, DHT is a paracrine hormone, so it doesn't need to travel through blood then reach the scalp to bind to the AR. 5ar in the scalp produces its own dht, separate from serum DHT. Thus RU58841, despite having lower affinity, cannot take the advantage of brute concentration force or direct application to scalp. 3. When dht binds to the receptor, it remains attached to it for a much longer amount of time than RU58841, thus activating the receptor and kickstarting the cascade of events that would lead to AGA progression. So we cannot trust RU58841 as a standalone treatment, however, we still need it for another purpose in our stack which I'll explain later. We will take dutasteride in this stack, not finasteride. Why? Because we need to maximize scalp dht reduction and only way to do this is through high dose dutasteride. We have to take 2.5 mg dutasteride daily, which reduces scalp dht by %79. In fact, if you can make a loading phase once per month (40 mg dutasteride) than use 2.5 mg per day in the remaining days of that month, you would probably achieve at least %90 scalp dht reduction but this may be expensive to do regularly.
The thing with DHT is that, despite being a byproduct of testosterone, dht has a unique molecular structure and some of the androgen signaling and cascade of events that happens are completely different than that of DHT. No amount of testosterone can make up for the loss of dht, even the supraphysiological doses. Only dht, and dht derivatives can achieve certain androgen signaling and cascade of events. These generally include; proper prostate function, cognitive function and mood regulation (low inhibition, bravery, mental power to deal with problems, DHT is also a neurosteroid that crosses brain-blood barrier.) orgasmic and ejaculatory function, penile sensation (DHT is crucial for penile nerve function.) Sufficient level of DHT is necessary for these functions to properly work. No amount of testosterone can compensate the lack of sufficient dht in those metrics since DHT and testosterone have different androgen signaling. That's why testosterone does not cause AGA contrary to popular belief. The cascade of events that happens when testosterone and DHT bind to AR in the scalp are different as well. In this step, we have a solution to lack of dht. This is where "mesterolone", a synthetic derivative of dht comes into play. It is also known as Proviron, which is the brand name under it's sold. You may know, rightfully, say that "Are you stupid? Why nuke DHT with dutasteride then replace it again with a synthetic form? What's the point?" The point is, mesterolone is a DHT derivative and when it binds to AR, it leads to same androgen signaling and cascade of events with DHT. However, mesterolone has a much lower binding affinity to AR than DHT. DHT's binding affinity is 2-3 times higher than testosterone, and masterelone's binding affinity is 2 times lower than testosterone despite leading to DHT-induced effects once activated the AR. Plus, DHT is an endogenous hormone, produced by testosterone's 5-a reduction, and DHT is a paracrine hormone, therefore found in high concentration in the tissues. (scalp in this example.) However mesterolone is a synthetic, exogenous hormone, in order for it to reach scalp and hair follicles, it has to travel in blood to scalp. Plus, it has 4 times lower binding affinity than DHT. But once it activated the receptor, it will lead to same effects as DHT. Unlike with DHT, RU58841 becomes useful here with mesterolone. DHT is paracrine but mesterolone is not, so only a tiny amount of it will reach scalp and since RU58841 will be directly applied to scalp, with a brute force due to its high concentration, RU58841 will easily outcompete mesterolone in the scalp thus prevent any possible mesterolone-induced aga progression. At the same time, mesterolone will bind to AR in the penis, prostate and cross brain-blood barrier and fully compensate the lack of dht in the body without inducing aga. From what I've calculated, a daily dose of 25 mg mesterolone (Proviron) is enough for that.
We all already know the basics of AGA, but I have to begin from scratch to build up to the point I want to make. DHT is the main culprit in AGA. All the other "blood flow" or "calcification" theories of AGA are either psuedo-scientific or just very negligible factors as long as DHT is addressed. They don't make sense on their own. It's the scalp dht that binds to androgen receptors in the hair follicles which causes miniaturization and therefore hair loss, serum dht and dht in other tissues are irrelevant. However, there is no way to effectively lower scalp dht levels without lowering the serum and local production of dht in other 5ar dense tissues, such as skin, prostate and penis. DHT is a paracrine hormone, which means that serum and local concentrations of DHT don't equally correspond. Topical finasteride goes systemic, it's been shown by numerous studies. Topical dutasteride would go systemic as well but the situation is even worse for it since due to the molecular weight of dutasteride, whether it penetrates the scalp skin effectively and works is still a debate topic. So, with the currently available set of drugs, we have to use an oral 5ar inhibitor. Now, you may ask; "What about RU58841?" RU58841 has indeed negligible systemic absorption which does not lead to any physiological effects when used at proper doses (50-75 mg per day). However, from what I've seen in the user anecdotes, RU58841 as a standalone monotherapy fails to treat AGA %99 of the time. There are two reasons for this: 1. RU58841 has %5 of the binding affinity of DHT to androgen receptor, which means DHT's binding affinity is 20 times higher than that of RU58841. 2. Unlike testosterone, DHT is a paracrine hormone, so it doesn't need to travel through blood then reach the scalp to bind to the AR. 5ar in the scalp produces its own dht, separate from serum DHT. Thus RU58841, despite having lower affinity, cannot take the advantage of brute concentration force or direct application to scalp. 3. When dht binds to the receptor, it remains attached to it for a much longer amount of time than RU58841, thus activating the receptor and kickstarting the cascade of events that would lead to AGA progression. So we cannot trust RU58841 as a standalone treatment, however, we still need it for another purpose in our stack which I'll explain later. We will take dutasteride in this stack, not finasteride. Why? Because we need to maximize scalp dht reduction and only way to do this is through high dose dutasteride. We have to take 2.5 mg dutasteride daily, which reduces scalp dht by %79. In fact, if you can make a loading phase once per month (40 mg dutasteride) than use 2.5 mg per day in the remaining days of that month, you would probably achieve at least %90 scalp dht reduction but this may be expensive to do regularly.
The thing with DHT is that, despite being a byproduct of testosterone, dht has a unique molecular structure and some of the androgen signaling and cascade of events that happens are completely different than that of DHT. No amount of testosterone can make up for the loss of dht, even the supraphysiological doses. Only dht, and dht derivatives can achieve certain androgen signaling and cascade of events. These generally include; proper prostate function, cognitive function and mood regulation (low inhibition, bravery, mental power to deal with problems, DHT is also a neurosteroid that crosses brain-blood barrier.) orgasmic and ejaculatory function, penile sensation (DHT is crucial for penile nerve function.) Sufficient level of DHT is necessary for these functions to properly work. No amount of testosterone can compensate the lack of sufficient dht in those metrics since DHT and testosterone have different androgen signaling. That's why testosterone does not cause AGA contrary to popular belief. The cascade of events that happens when testosterone and DHT bind to AR in the scalp are different as well. In this step, we have a solution to lack of dht. This is where "mesterolone", a synthetic derivative of dht comes into play. It is also known as Proviron, which is the brand name under it's sold. You may know, rightfully, say that "Are you stupid? Why nuke DHT with dutasteride then replace it again with a synthetic form? What's the point?" The point is, mesterolone is a DHT derivative and when it binds to AR, it leads to same androgen signaling and cascade of events with DHT. However, mesterolone has a much lower binding affinity to AR than DHT. DHT's binding affinity is 2-3 times higher than testosterone, and masterelone's binding affinity is 2 times lower than testosterone despite leading to DHT-induced effects once activated the AR. Plus, DHT is an endogenous hormone, produced by testosterone's 5-a reduction, and DHT is a paracrine hormone, therefore found in high concentration in the tissues. (scalp in this example.) However mesterolone is a synthetic, exogenous hormone, in order for it to reach scalp and hair follicles, it has to travel in blood to scalp. Plus, it has 4 times lower binding affinity than DHT. But once it activated the receptor, it will lead to same effects as DHT. Unlike with DHT, RU58841 becomes useful here with mesterolone. DHT is paracrine but mesterolone is not, so only a tiny amount of it will reach scalp and since RU58841 will be directly applied to scalp, with a brute force due to its high concentration, RU58841 will easily outcompete mesterolone in the scalp thus prevent any possible mesterolone-induced aga progression. At the same time, mesterolone will bind to AR in the penis, prostate and cross brain-blood barrier and fully compensate the lack of dht in the body without inducing aga. From what I've calculated, a daily dose of 25 mg mesterolone (Proviron) is enough for that.
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