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Study: This is why the top of the head is most affected by baldness. But how to repair that bald patch?

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Male pattern baldness explained – 21st century

The reason why men are more affected by hair loss than women seems relatively easy to explain.

For one thing, testosterone permanently increases adrenal gland size at an early age.

This leads to higher cortisol output in males on average. Especially in response to stress.

Androgens also lead to sex‐specific immune changes through their effects on the thymus gland.

And this leads to a higher TH1/TH2 ratio, which increases interferon‐γ. Interferon‐γ is a cytokine which upregulates prostaglandin enzymes such as those found in hair loss.

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But why does hair loss affect that particular area of the head?

That is more difficult to explain.

I think we all know intuitively that blood flow has something to do with this. But how?

Hints can be found by looking at the things most correlated with hair loss.

Luis Garza showed in 2012 that…

…prostaglandin D₂ is consistently higher in bald areas.

He found that the enzyme that makes it (prostaglandin D₂ synthase) was higher in the areas corresponding to the prostaglandin itself.

He also found that the mRNA which encodes prostaglandin D₂ synthase was upregulated and highly‐correlated with the other two.

And prostaglandin D₂ causes hair loss when applied directly.

More research has confirmed this connection:

Following up on Garza’s study, a team of researchers measured the skin gradient from the lower part of the head towards the apex.

They noted whether or not the area had hair. They also tested for prostaglandin D₂ synthase.

The found a near-perfect correlation between prostaglandin D₂ synthase and the hairless areas.

Prostaglandin D₂ synthase concentration actually increases in a gradient the further up the head.

Nothing correlates to baldness more closely than prostaglandin D₂ synthase.

Many people may be satisfied with that single observation, but it doesn’t explain why prostaglandin D₂ synthase is higher in the first place.

Let’s start with how prostaglandin D₂ synthase is created.

The only thing shown to transcribe prostaglandin D₂ synthase is a transcription factor named SOX9.

Which is activated directly by cortisol.

Since only cortisol appears to have the ability to create prostaglandin D₂ synthase…

You might expect the cortisol gradient to be identical to the prostaglandin D₂ gradient.

And there’s a logical reason to think so:

Near the vertex of the scalp, we have microcirculation – very small blood vessels (much smaller than could be resolved in creating the model below).

This is where the arterial supply ends.

But there’s no less blood here. The same amount of blood that passes through the larger vessels must reach the apex somehow.

The difference is the number, radius, and total surface area of the vessels.

The top of the head is a microcirculatory region.

And it’s been proven that microcirculatory regions have increased hormone transport.

This is because the proteins that cortisol binds to (such as albumin and corticosteroid binding globulin) have binding areas on the inside.

“The interior of the hemicylinder acts as the binding site, and albumin is a highly flexible molecule.” 

This protects the cortisol until it rubs up against the side of a blood vessel, at which point it’s released.

This process has been noted for decades.

For example, this is how scientists commonly explain enhanced steroid transfer through microvessel areas.

Here’s an equation that relates surface area, volume, length, and radius.

(With volume held constant and with length not decreasing – physiological preconditions.)

SA = (⁸⁄₃)V·l/r²

With decreased radius, you must get an increase in surface area.

So there’s more interaction between hormones and vessel walls.

More surface area of blood vessels means more interaction with cortisol-binding proteins. Hence a greater hormone transfer rate.

This has been experimentally proven at the blood-brain barrier, where tiny blood vessels greatly increase the rate of steroid transport.

“Testosterone dissociation is increased fiftyfold in the brain microcirculation, whereas corticosterone dissociation from bovine albumin is increased…”

So, smaller blood vessels at the top of the head result in more albumin blood vessel interaction.

This leads to greater hormone transport, more prostaglandin enzyme, prostaglandin D₂, and, voilà: hair loss.

The liver has a microcirculatory system as well – to filter the blood.

Based on this fact alone, you could expect the top of the head to have more steroid hormones, more cortisol, and more prostaglandin D₂ synthase.

“A conformational change about the albumin-binding site would result in a partial uncoiling about the binding site and markedly increase rates of hormone dissociation.”

Scientists take things like this seriously.

Here is a study showing how quickly brain microcirculation can strip tryptophan off albumin:

As a side note, brain tryptophan is where all serotonin is derived from.

To find out how much is absorbed in one pass, the scientists loaded up albumin with radioactive tryptophan.

They injected this into an artery leading to the heads of experimental rabbits and cut their heads off after 15 seconds.

Then they measured for radioactive tryptophan as quickly as possible.

This is just one of the dozens of studies showing that free hormone concentrations hardly matter.

What matters is total hormone concentration.

Hormones are stripped off their binding proteins all the time, and at greater rates, in microcirculatory areas.

This is how the liver increases its filtering rate, how the brain gets more than its fair share of hormones, and very likely why the vertex of the head gets more cortisol.

It’s an evolutionary accident.

But prostaglandin D₂ synthase can’t cause hair loss on its own.

It needs help from linoleic acid.

Linoleic acid is essential to form the arachidonic acid needed for prostaglandin formation.

“This suggests that other environmental factors are probably at play, impacting which people go on to develop alopecia.”

So male pattern hair loss might best be seen as primarily a mix of cortisol and linoleic acid operating together.

With cytokines such as interferon‐γ playing a supporting role

—–Important Message—–

Single men: Creating desire in a girl

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Matt Cook is editor-in-chief of Daily Medical Discoveries. Matt has been a full time health researcher for 26 years. ABC News interviewed Matt on sexual health issues not long ago. Matt is widely quoted on over 1,000,000 websites. He has over 300,000 daily newsletter readers. Daily Medical Discoveries finds hidden, buried or ignored medical studies through the lens of 100 years of proven science. Matt heads up the editorial team of scientists and health researchers. Each discovery is based upon primary studies from peer reviewed science sources following the Daily Medical Discoveries 7 Step Process to ensure accuracy.