How Type I and Type II 5-Alpha Reductase Differ ── The Enzyme Mechanism That Changes How Crown and Frontal Hair Loss Progress, and Stem Cell Conditioned Media as a Medical Option2026.06.26
“I have been on oral medication for a year — my crown looks better, but my hairline still hasn’t improved.” “Why is it that two men with the same AGA diagnosis lose hair in different places?” The key to these questions lies in a single enzyme: 5-alpha reductase. The essence of AGA (androgenetic alopecia) is found in the metabolism of male hormones and the sensitivity of hair follicles, and this enzyme sits at the very center of that pathway. In this article, Dr. Shin Moriwaki of AVAN TOKYO Ginza Hair Regenerative Medicine explains, from a medical perspective, how the two isozymes — Type I and Type II — differ, and why the pattern of thinning varies between the crown and the frontal hairline.
What Is 5-Alpha Reductase? — The Enzyme at the Center of AGA
5-alpha reductase is the enzyme that converts testosterone into dihydrotestosterone (DHT) inside the body. DHT has roughly 2.5 to 10 times the androgenic potency of testosterone, and it is the principal driver of the follicular miniaturization, shortened hair cycle, and vellus-hair transition seen in AGA.
Type I and Type II Were Discovered as Separate Enzymes
This enzyme exists as two major isozymes — Type I and Type II — which are different proteins that happen to catalyze the same reaction. Genetic cloning research in the 1990s showed that they are encoded at different loci on different chromosomes and differ in both structure and properties. Although both produce DHT, where they predominantly act in the body is markedly different.
Differences in Distribution Within the Body
Type II is highly expressed in the prostate, seminal vesicles, frontal and crown follicles, beard, and body-hair follicles. Type I, on the other hand, predominates in the sebaceous glands, liver, and the follicles of the temporal and occipital scalp. This distribution difference is precisely what determines the clinical face of AGA — namely, where balding begins.
Why the Crown and Frontal Hairline Thin Differently
It is no coincidence that AGA tends to progress from the frontal hairline (the M-shape) and the crown while sparing the temporal and occipital regions. This pattern can be explained scientifically by differences in the type and amount of enzyme present in the follicles and by the hormonal sensitivity of follicular cells.
Type II Dominates the Frontal and Crown Regions
Follicles from the frontal hairline to the crown express high Type II 5-alpha reductase activity, efficiently converting testosterone into DHT. Furthermore, follicular cells in these areas have heightened androgen-receptor sensitivity, so DHT acts directly on matrix cells and progressively shortens the anagen phase of the hair cycle. The familiar AGA pattern — “receding from the hairline,” “thinning starting at the whorl” — is the inevitable consequence of this enzyme distribution.
The Sides and Back Are Type I–Dominant and “Last to Go”
The follicles of the temporal and occipital scalp, by contrast, are Type I–dominant, with low Type II activity and lower androgen-receptor sensitivity. This is the biological basis of donor dominance in autologous hair transplantation — “we harvest from the back of the head.” Even after transplantation, occipital hairs largely retain their resistance to androgenic influence.
AGA Medications and the Enzyme — Finasteride vs. Dutasteride
Understanding isozyme distribution directly informs the choice of AGA medication.
Finasteride: Selective Type II Inhibition
Finasteride (Propecia®) selectively inhibits Type II. Because the crown and frontal scalp are Type II–dominant, finasteride targets the very core regions of AGA. However, it scarcely suppresses Type I, so DHT generated by the sebaceous glands and the contribution of Type I to other regions are not fully addressed.
Dutasteride: Dual Type I + Type II Inhibition
Dutasteride (Avodart®/Zagallo®) is a dual inhibitor that blocks both Type I and Type II. It suppresses circulating DHT more strongly than finasteride and also blocks Type I–derived DHT, making it a choice for cases where finasteride proves insufficient. Both drugs share concerns regarding sexual function and mood, as well as a strict contraindication for contact in women of childbearing potential. For clinical guidelines on AGA treatment, please also refer to the Japanese Dermatological Association.
The “Limit” of 5-Alpha Reductase Inhibitors and Stem Cell Conditioned Media as an Option
A clinically important point is that 5-alpha reductase inhibitors are essentially treatments that “shut off the upstream cause” — DHT — but have almost no power to reawaken follicles that have already miniaturized or entered the resting phase. For patients who show little improvement after one to two years on oral therapy, who cannot tolerate the side effects, or for women with FAGA, a different approach that acts directly on the follicle itself becomes necessary.
Stem cell conditioned media is the supernatant of cultured human adipose-derived stem cells, containing a cocktail of growth factors such as VEGF, IGF-1, HGF, and KGF, together with exosomes. It acts directly on the niche of follicular stem cells and promotes the reactivation of follicles that have entered the resting phase. If 5-alpha reductase inhibitors are a “subtractive treatment that lowers DHT,” then stem cell conditioned media is an “additive treatment that restores follicular regenerative capacity.” The two do not compete; on the contrary, combining them reaches territory that oral medication alone cannot.
At AVAN TOKYO, we use Morpheus8 microneedle RF to create fine microchannels in the scalp, then deliver conditioned media directly into the follicular microenvironment — the very layer that enzyme inhibitors fail to reach — via a drug-delivery protocol.
Conclusion — AGA Is a “Scientifically Explainable Phenomenon”
AGA is not simply “genetics”; it is a scientifically explainable phenomenon governed by the distribution and activity of the 5-alpha reductase enzyme. Understanding the difference between Type I and Type II distribution allows the pattern of your own thinning, and the way your medication responds, to make sense — and enables you to choose the “next move” on medical grounds.
When inhibitor therapy gives insufficient response, when side effects make oral medication difficult to continue, or when oral therapy is hard to choose in women with FAGA, stem cell conditioned media offers a complementary option. View related columns on hair regenerative medicine here.
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【監修】森脇 進 / Shin Moriwaki（監修医師）
日本美容外科学会(JSAS)会員 / American Academy of Aesthetic Medicine 会員
米国医師免許資格(ECFMG certificate)
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📍AVAN TOKYO 銀座 毛髪再生医療
AVAN TOKYO Ginza Hair Regenerative Medicine
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