Morning everybody.

I get some version of this question almost every week now.

"Nico, what concentration of topical finasteride has the least systemic absorption but still works on the scalp?"

It's a good question.

But I want to tell you up front that I don't reach for this drug much, and I'm going to explain why.

Especially orally, and especially in men.

First, let me back up for anyone who doesn't prescribe this every week.

Finasteride blocks an enzyme called 5-alpha reductase.

That enzyme converts testosterone into dihydrotestosterone, or DHT. DHT is the androgen most involved in scalp hair loss and prostate growth, so finasteride got approved for male pattern hair loss and for enlarged prostate. Block the enzyme, lower DHT, slow the hair loss, and so on and so forth.

On paper it's clean and sincerely effective.

The problem is what else that enzyme does.

DHT is not a waste product.

It's the most potent androgen at the receptor, stronger than testosterone itself. It drives libido, erectile function, mood, motivation, and dopaminergic tone. When you suppress it systemically, you're creating a literally mountain out of a molehill.

And if that's not bad enough, here's the part most people miss.

5-alpha reductase doesn't only make DHT.

It's also a key enzyme in the pathway that turns progesterone into allopregnanolone.

Allopregnanolone is a neurosteroid. It's one of the strongest positive modulators of the GABA-A receptor we make. Calming. Anxiolytic. Sleep-promoting.

So when you inhibit 5-alpha reductase, you don't just drop DHT. You also drop a calming neurosteroid.

That's the mechanistic story underneath the mood changes, the anxiety, the flat affect, the brain fog, and the sexual complaints that a subset of men report on finasteride. It's the same mechanism behind what gets called post-finasteride syndrome, where the symptoms persist after the drug is stopped.

Is that every patient? No.

Most men tolerate it. But the men it happens to are not imagining it, and the mechanism is right there in the enzyme.

So that's my bias.

For most men, trading a potent androgen and a calming neurosteroid for a hairline is not a deal I love. And oral finasteride is the version that makes that trade the practically impossible for me to stomach.

Here's why the route matters so much.

Oral finasteride 1 mg drops serum DHT about 71% and scalp DHT about 64% (Drake, JAAD, 1999).

So the scalp effect and the systemic effect are basically the same size.

You cannot get the hair benefit from the pill without suppressing DHT everywhere else at nearly the same magnitude.

That's the whole problem with oral, especially in men.

Now, some of you are already thinking the obvious.

What about microdosing it?

Fair. And this is where it gets interesting.

Finasteride's effect on DHT plateaus at a shockingly low dose. Drake's dose-ranging data showed 0.2 mg a day suppressed scalp and serum DHT almost as much as the full 1 mg. Crazy right?

Serum DHT fell about 69 percent at 0.2 mg versus 71 percent at 1 mg. Even 0.05 mg a day dropped serum DHT roughly 50 percent.

And the hair benefit tracks that plateau. A 414-man, 48-week randomized trial found 0.2 mg daily worked about as well as 1 mg.

So microdosing looks great on the surface. Same hair, less drug.

But look at those systemic numbers again.

At 0.2 mg you're still down about 70 percent on serum DHT. At a true microdose of 0.05 mg you're still down around half.

That's the catch.

The reason tiny doses still grow hair is the same reason they still hit you systemically.

The enzyme saturates almost immediately.

Taking less doesn't buy you a clean local effect. It just slides you a little way down a curve that flattened out a long time ago.

In that same 414-man trial, going from 1 mg to 0.2 mg only moved reported libido complaints from about 3 percent to about 1.5 percent. Real, but modest.

Unfortunately, spacing it out doesn't rescue you either.

Finasteride binds 5-alpha reductase for weeks, so DHT stays suppressed long after a dose.

The "off" days aren't really off. And the every-other-month maintenance data is thin and mixed, with the spaced-out group actually losing some density and drifting back up on DHT.

So here's my honest take on oral microdosing.

It lowers your total exposure, sure.

BUT it doesn't spare the pathway the way people hope.

If the whole goal is to keep DHT and that calming neurosteroid effect close to intact, the microdose that actually does it isn't a smaller pill.

It's low-volume topical.

Which is exactly where I was headed. Because this is where the original question finally comes in. Which concentration is safest?

But that's the wrong variable.

Concentration is not what decides your systemic exposure. Dose and frequency are.

And if you want to read how I dissect this variable, then you're not going to want to miss Friday's email.

That's when I'll give you my best take on topical finasteride.

-Nico

PS

Androgens, DHT, and how molecule, dose, and route change the entire picture sit right in the middle of what we work through in the HRTU Master Course. If you want the full physiology-first framework behind emails like this one, the six-module, 30-CEU course is here: hrtuniversity.com/hrtcourse​