the MOUSE
Bones don't lie, Mosley. See you in Animal Park
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There is too much we don’t know to claim that DHT causes hair loss.
There are also too many paradoxes and it’s much too reductionistic for DHT alone to cause/contribute to hair loss.
General knowledge has risen to the point where a lot of independent researchers on the internet are saying that DHT doesn’t cause hair loss, but is only contributing to it.
I’m not denying that DHT or androgen receptors are elevated in the scalp.
We know that circulating DHT isn’t a good marker for hair loss, and now it’s the 5AR in the scalp specifically that boosts DHT locally that contributes to hair loss (that’s what people believe). That’s why DHT is found to be generally (not in everyone) increased in the scalp of balding men.
Furthermore, the androgen receptor becomes upregulated in some people who are balding, so even if they have normal DHT, they can still suffer balding…or so the theory goes.
But as I mentioned, DHT doesn’t cause hair loss. This is supported by the fact that men who are exposed to exceptionally high levels of DHT in response to the daily application of DHT for a long period of time didn’t experience acne, male androgenic alopecia or other androgen-associated skin pathology (R).
Something else is driving hair loss.
However, here is an in vitro human hair follicle and animal study showing that certain concentrations of DHT actually promote the regrowth of hair (R).
“In our study, we found a similar phenomenon: when the DHT concentration decreased from 10-6 mol/L to 10-7 mol/L, the HFs grew much better than in the presence of higher DHT concentrations. In fact, the results suggest that an appropriate level of DHT is required for normal androgen-sensitive HF growth. Once the DHT concentration decreased from 10-7 mol/L to 10-8 mol/L, the HF growth rate showed no significant difference from that in the control group, which explains why beard growth is weaker in castrated males.“
There is a paradox that DHT promotes hair growth everywhere else in the body except on the top of the scalp. However, the above study found that DHT should even promote hair growth on the top of the scalp as well.
So clearly, DHT on its own doesn’t promote hair loss.
Some studies show that IGF-1 is decreased in balding men whereas others show that it’s increased.
5AR is IGF-1 dependent (R), so if free IGF-1 goes too high, then DHT also goes up as well. IGF-1 seems to prevent hair loss and even promote hair regrowth, so if IGF-1 boosts DHT, shouldn’t IGF-1 also be bad?
However, it’s the dysregulation of the IGF-1 axis that promotes hair loss. Some studies find that IGFBP2 and 4 are low, whereas others find IGFBP-3 (IGFBP-3 influences the bioavailability of
IGF-1) low (R). DHT (much more than testosterone) has actually been shown to increase IGFBP-3, so it should actually improve hair quality (R).
And in turn, androgens increase IGF-1 mRNA (R). So if IGF-1 is good, DHT should also be good since it boosts IGF-1.
Why does it work for some people?
Some people get an increase in IGF-1, which seems to be the helpful factor (R). Those without a change in IGF-1 didn’t experience benefits.
As I mentioned to Sam Empie in our podcast, the effects of finasteride are totally understudied. For example, when they design an SSRI drug (or any other drug really), they think it has only one function, but later on, it turns out that it has many other effects as well.
Similarly, finasteride has been thought to only inhibit 5-AR, but now it’s known that it also increases IGF-1 for some people as well. What other “beneficial” effects does it not also have.
We know about its side effect, which there is an extensive list of, but will we ever know why it really worked for some people? Most likely not, because the scientists think they have the mechanism of action figured out. But their hypothesis is wrong.
DHT doesn’t cause hair loss. Most people that have hair loss also have other comorbidities, such as cardiovascular disease, diabetes, metabolic syndrome, gastrointestinal problems, etc.
Actually, a few studies have found that balding men are significantly more likely to get severe symptoms from COVID (R, R).
And this is because balding men are often not healthy and hair loss is just a sign/symptom of that.
There are also too many paradoxes and it’s much too reductionistic for DHT alone to cause/contribute to hair loss.
General knowledge has risen to the point where a lot of independent researchers on the internet are saying that DHT doesn’t cause hair loss, but is only contributing to it.
DHT in hair loss
I’m not denying that DHT or androgen receptors are elevated in the scalp.
We know that circulating DHT isn’t a good marker for hair loss, and now it’s the 5AR in the scalp specifically that boosts DHT locally that contributes to hair loss (that’s what people believe). That’s why DHT is found to be generally (not in everyone) increased in the scalp of balding men.
Furthermore, the androgen receptor becomes upregulated in some people who are balding, so even if they have normal DHT, they can still suffer balding…or so the theory goes.
But as I mentioned, DHT doesn’t cause hair loss. This is supported by the fact that men who are exposed to exceptionally high levels of DHT in response to the daily application of DHT for a long period of time didn’t experience acne, male androgenic alopecia or other androgen-associated skin pathology (R).
Something else is driving hair loss.
However, here is an in vitro human hair follicle and animal study showing that certain concentrations of DHT actually promote the regrowth of hair (R).
“In our study, we found a similar phenomenon: when the DHT concentration decreased from 10-6 mol/L to 10-7 mol/L, the HFs grew much better than in the presence of higher DHT concentrations. In fact, the results suggest that an appropriate level of DHT is required for normal androgen-sensitive HF growth. Once the DHT concentration decreased from 10-7 mol/L to 10-8 mol/L, the HF growth rate showed no significant difference from that in the control group, which explains why beard growth is weaker in castrated males.“
There is a paradox that DHT promotes hair growth everywhere else in the body except on the top of the scalp. However, the above study found that DHT should even promote hair growth on the top of the scalp as well.
So clearly, DHT on its own doesn’t promote hair loss.
DHT in balding men
- DHT blockage doesn’t reverse hair loss (doesn’t promote regrowth), only stops further hair loss to a degree.
- DHT doesn’t cause calcification on its own. Calcification in implicated in hair loss.
- Since there is a decrease in 5alpha-reductase activity in senescent alopecia, efficacy of the 5alpha-reductase inhibitors decreases in men after the age of 60 years (R).
A few questions on the logic of DHT and hair loss
- What causes 5AR, DHT and ARs to increase in androgenic alopecia-prone tissues?
- By which mechanisms does DHT miniaturize androgenic alopecia-prone hair follicles, since DHT does not directly (or on its own) miniaturize hair follicles.
- Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not reverse it?
- Androgens doesn’t contribute to cardiovascular disease (it actually reverses it), so why would it do so in the scalp?
- In prostate tissue (a highly androgen sensitive tissue), DHT is shown to exert broad anti-inflammatory effects (R). Why is it inflammatory (the opposite) in the scalp? Since ROS promotes androgen receptor signalling in the prostate, it should do the same in the scalp and actually be the root cause of the hair loss (R).
- Why does DHT only cause hair loss in that specific pattern? Why does only the hair follicles on top of the scalp increase 5AR and not all the scalp hair follicles?
- When they do in vitro studies on human hair follicles, do they use the top or the side follicles, or does it not matter? Isn’t it impossible to actually descern if DHT is the culprit or not since there is no difference in vitro? As a side note, it’s difficult to assess the influence of 5AR on hair follicle growth because 5AR cannot be maintained in culture systems in vitro (R).
IGF-1, DHT and hair loss
Some studies show that IGF-1 is decreased in balding men whereas others show that it’s increased.
5AR is IGF-1 dependent (R), so if free IGF-1 goes too high, then DHT also goes up as well. IGF-1 seems to prevent hair loss and even promote hair regrowth, so if IGF-1 boosts DHT, shouldn’t IGF-1 also be bad?
However, it’s the dysregulation of the IGF-1 axis that promotes hair loss. Some studies find that IGFBP2 and 4 are low, whereas others find IGFBP-3 (IGFBP-3 influences the bioavailability of
IGF-1) low (R). DHT (much more than testosterone) has actually been shown to increase IGFBP-3, so it should actually improve hair quality (R).
And in turn, androgens increase IGF-1 mRNA (R). So if IGF-1 is good, DHT should also be good since it boosts IGF-1.
Finasteride on hair loss
Why does it work for some people?
Some people get an increase in IGF-1, which seems to be the helpful factor (R). Those without a change in IGF-1 didn’t experience benefits.
As I mentioned to Sam Empie in our podcast, the effects of finasteride are totally understudied. For example, when they design an SSRI drug (or any other drug really), they think it has only one function, but later on, it turns out that it has many other effects as well.
Similarly, finasteride has been thought to only inhibit 5-AR, but now it’s known that it also increases IGF-1 for some people as well. What other “beneficial” effects does it not also have.
We know about its side effect, which there is an extensive list of, but will we ever know why it really worked for some people? Most likely not, because the scientists think they have the mechanism of action figured out. But their hypothesis is wrong.
Conclusion
DHT doesn’t cause hair loss. Most people that have hair loss also have other comorbidities, such as cardiovascular disease, diabetes, metabolic syndrome, gastrointestinal problems, etc.
Actually, a few studies have found that balding men are significantly more likely to get severe symptoms from COVID (R, R).
And this is because balding men are often not healthy and hair loss is just a sign/symptom of that.
