Dihydrotestosterone (DHT) is an androgen hormone produced in the body when testosterone interacts with the enzyme 5-alpha-reductase. It’s far more prevalent in men, but also found in smaller amounts in women.
It’s been assumed for many years that DHT is the cause of male pattern baldness (MPB). There’s a lot of evidence for this: A greater volume of DHT is found in bald and balding scalps. A greater number of androgen receptors is found in bald and balding scalps. Treatments like Finasteride and RU58841 reduce DHT and androgen receptors and they work.
Balding cells contained significantly (P 0.01) greater levels of androgen receptors (Bmax = 0.06 +/- 0.01 fmol/10(4) cells (mean +/- S.E.M.)) than those from non-balding scalp (0.04 +/- 0.001).Via PubMed
It’s generally accepted that DHT causes MPB in the scalp when it binds with androgen receptors in the hair follicles. But very few people actually know why and how DHT causes hair loss in the scalp. And that is extremely important. Because if you understand how DHT causes hair loss, I believe you’ll understand the underlying link between all types of hair loss.
How exactly does DHT cause hair loss?
According to a very thorough and hugely impressive write up by Jankovic and Jankovic for the Dermatology Online Journal, DHT causes an increase in inflammatory cytokines:
Androgens indirectly control hair growth by influencing the synthesis and release of cytokines from the dermal papilla cells
Cytokines are powerful inhibitors of scalp hair growth. See my article on cytokines for my explanation.
What’s really interesting about this is that various other forms of hair loss, including alopecia areata, are thought to be largely caused by inflammatory cytokines and several alopecia patients have responded well to cytokine inhibitors, JAK inhibitors and PGD2 inhibitors. It seems as though the inflammatory and/or immune response in the scalp follicles is a recurring theme common to many (perhaps even all) types of hair loss.
Inflammation causes perifollicular fibrosis
Inflammation and immune response alone is enough to cause some types of hair loss (and perhaps even some MPB is entirely due to an immune response triggered by DHT binding to receptors), but I suspect most of the irreversible MPB is caused by perifollicular fibrosis.
Chronic inflammation of the hair bulge gradually leads to irreversible scarring of the follicle, which we call ‘perifollicular fibrosis’. It’s pretty clear why this causes hair follicle miniaturization, a receding hairline, a bald spot and eventually total loss of hair on the top of the head. It makes sense that the follicles morphing from healthy to irreversibly damaged would result in the slick, shiny, tight scalp appearance of bald men.
But it’s all very well saying DHT causes inflammation, which may lead to extensive perifollicular fibrosis, causing irreversible damage to the hair follicles; but it still doesn’t answer the original question: Why does DHT set this destructive process in motion in some people and not others?
Fibrosis typically results from chronic inflammation — defined as an immune response that persists for several months and in which inflammation, tissue remodelling and repair processes occur simultaneously
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It’s the prolonged immune response that we’re really interested in here.
And here’s where it gets really interesting
I have suspected for a long time that stress plays an important role, even in androgenic alopecia. Why? Because it has always seemed to me that lazy, bone-idle, carefree men never lose their hair! Whereas thoughtful, troubled intellectuals seem to suffer the worst of it.
Think Leonardo Divinci, Steve Jobs, James Gandolfini and many more troubled minds.
The actor James Gandolfini, by the way, has publicly said he spent his whole life battling anxiety, while simultaneously constantly trying to build a career in the spotlight. You can see how this would be incredibly stressful. So too has the actor the Dwayne Johnson, who also has an entirely slick bald head. See my article on Dwayne Johnson and James Gandolfini.
Of course there are anomalous individuals who don’t fit the pattern. There are always anomalies. But in general, just take a look at the men you know or see about. It’s the lazy, carefree, untroubled (slightly dumb) ones who seem to never lose their hair. While, generally; stressed, intelligent or introverted individuals seem to lose their hair extremely prematurely. The relaxed, carefree men might have full thick beards caused by high DHT, but no scalp hair loss.
You’re probably thinking, OK you started out citing some credible research and making a lot of sense. Now you’re verging into wacky territory. Well, think again. It just so happens there’s a lot of credible research that backs-up what I just said (albeit far more concisely and eloquently).
The reason DHT causes scalp hair loss
As I’ve already mentioned; bone idle, lazy oafs don’t tend to lose their hair. But is that because they have lower DHT levels or because DHT affects their scalp hair differently; or is it something else?
I suspect calm, less stressed people have similar DHT profiles to stressed people but it’s how the DHT affects the hair follicles in a less damaging way that’s the reason for the lower instances of hair loss in less stressed individuals.
DHT causes increased inflammatory cytokines in the scalp follicles. Certain types of stress also cause increased inflammatory cytokines.
If the inflammation (which also leads to perifollicular fibrosis) is ultimately what destroys the hair follicles, then it seems to make sense that individuals with both high levels of DHT related inflammation and high levels of stress-related inflammation have such high overall scalp follicle inflammation that the damage to follicles is greatly accelerated, leading to premature hair loss.
Is there any evidence for this hypothesis?
Women are less likely to lose their hair than men. Although women might experience similar stressors as men, they should have less perifollicular inflammation because of lower DHT. Similarly, some men might have very high DHT levels but never lose their hair. Could this be because, although they have the inflammation caused by DHT, they have far less of the stress-related inflammation?
Perhaps there is some significant interaction between chemical signals communicated by stress-induced cytokines and DHT induced cytokines that lead to high levels of TGFbeta1 and 2 – the transforming growth factors that cause hair follicles to transition from anagen to catagen.
Stress alone is enough to cause hair loss in some cases. DHT alone is enough to cause hair loss in some cases. These cases, I imagine, are the outliers in the data. I suspect the bulk of cases are those that have both DHT and stress-related perifollicular inflammation combined at such a level to cause uncontrollable hair loss (or at least hair loss that’s hard to control without effective treatments).
You might think that the cause is not important, providing you know how to treat it. I.e. it doesn’t matter how DHT causes hair loss because we can reduce DHT and block androgen receptors and that stops male pattern hair loss. However, I believe it’s extremely important to understand the answer to this question:
Why does DHT cause hair loss in some scalps and not others?
When you think about it, this really asks for the true cause, because DHT isn’t really the cause of male pattern hair loss if it doesn’t cause all men to lose their hair. Instead, there is a more specific interaction involving DHT that causes MPB. I believe the extra part for the equation is steroidal stress hormones: cortisol and perhaps others.
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And since there is some hypothetical content in this article, please feel free to post a comment to discuss.