Follicle Miniaturization, Step by Step

By Dr. Susan Lin, MD | MD HAIR | La Cañada Ventures, Inc.
Published on mdhair.com — Verbascoside & Lilac Science Series

You did not lose your hair. That is the part nobody explains, and it is why the mirror confuses you.

Count the follicles on a thinning scalp and you find, for a long time, very nearly the same number as before. The parting looks wider. The ponytail has gone from three fingers to two. The light comes through at the crown in a way it did not last year. And yet the follicles are still there — most of them, in most people, for years.

What changed is not how many. It is how big.

Miniaturization is the slow conversion of a thick, pigmented, long-growing terminal hair into a fine, pale, short-lived one, over successive cycles, in the same follicle. It is the central event of pattern hair loss in both women and men, and it is the reason this condition creeps rather than announces itself.

I am Dr. Susan F. Lin, M.D. — Boston University School of Medicine, board-certified in Obstetrics & Gynecology and in Anti-Aging Medicine, and the physician behind the MD® line at La Cañada Ventures, Inc. since 2008. This article walks the process step by step, and then does the harder thing: it tells you where in that sequence intervention is plausible, and where it is not. There is a point past which no cosmetic and no supplement — mine included — is going to bring a follicle back, and you deserve to know where it is.

First, the Vocabulary That Actually Means Something

Three words do most of the work.

Terminal hair. Thick, pigmented, medullated, long-growing. On the scalp, generally taken as greater than about 60 micrometres in shaft diameter. This is what you think of as your hair.

Vellus hair. Fine, unpigmented or barely pigmented, short. Generally under about 30 micrometres, and produced by a small follicle sitting shallowly in the dermis. Everyone has vellus hair — on the forehead, the cheeks, most of the body. It is normal. It is simply not what you want on your scalp.

Indeterminate hair. Everything between. This is the diagnostically interesting category, because a scalp with a lot of indeterminate hairs is a scalp with follicles in transit — caught mid-miniaturization.

Clinically this is measured as the terminal-to-vellus ratio on a horizontal scalp biopsy section. Whiting's work on horizontal sectioning established the method and its diagnostic value: a normal scalp runs a high ratio of terminal to vellus-sized hairs, and a substantially reduced ratio is characteristic of androgenetic alopecia (Whiting, 1993; Headington, 1984). A dermatologist looking at that section is not counting how much hair you have. She is counting what proportion of your follicles are still building terminal fibres.

That is the disease, stated precisely. Not absence. Downgrading.

The Sequence, Step by Step

Miniaturization is not one event. It is a loop that runs slightly worse each time around.

Step 1 — Androgen reaches a susceptible follicle

Testosterone is converted to dihydrotestosterone by 5-alpha-reductase locally, in scalp skin and hair follicles. Both isoforms of the enzyme are present and measurable in the human scalp follicle system, with differences between men and women (Sawaya & Price, 1997); immunohistochemistry localises Type 2 within follicle structures and Type 1 predominantly in sebaceous glands (Bayne et al., 1999).

The critical variable is not usually how much DHT you make. It is how sensitive that particular follicle is — which is why the process is regionally patterned, sparing the occipital scalp and the sides while affecting the vertex and frontal scalp in the same person, on the same hormones, at the same time.

Step 2 — The dermal papilla changes what it says

Androgen acts at the dermal papilla, the cluster of mesenchymal cells at the follicle's base that governs anagen duration and fibre calibre. The papilla is where the androgen receptor is expressed; the hair-building matrix keratinocytes above it are not the primary androgen-responsive cells.

So the effect is paracrine: hormone binds in one cell type, which then alters the diffusible signals it sends to another (Inui & Itami, 2011). Two of those mediators are well characterised. DHT induces DKK-1 in balding-scalp dermal papilla cells, and DKK-1 causes apoptosis in follicular keratinocytes (Kwack et al., 2008). TGF-β2, also papilla-derived, has been implicated in driving the human follicle out of its growth phase (Hibino & Nishiyama, 2004).

Read that again with the anatomy in mind. The signal arrives at the command centre, and the command centre issues an instruction that damages the workforce.

Step 3 — Anagen shortens

The direct consequence. A follicle that ran a six-year growth phase now runs five, then three, then eighteen months, then months.

This alone changes what you see, because hair length is growth rate multiplied by anagen duration, and growth rate barely moves. Shorter anagen means the hair is released before it reaches the length it used to reach. Hair that won't grow past the shoulders any more is very often not breakage. It is a shortened growth phase.

Step 4 — The papilla itself gets smaller

This is the step that makes the loop progressive rather than merely repetitive.

Papilla cell number correlates with the volume of hair a follicle produces. Under sustained androgen and inflammatory pressure, papilla cell number falls — and because the papilla is the template from which the entire lower follicle is rebuilt at the start of every cycle, the follicle regenerates itself smaller each time (Whiting, 2001; Stenn & Paus, 2001).

The regeneration is faithful. That is precisely the problem: it faithfully reproduces a diminished instruction.

Step 5 — The matrix shrinks, and so does the fibre

A smaller papilla instructs a smaller matrix, which builds a narrower shaft with less pigment. Terminal becomes indeterminate. Indeterminate becomes vellus-like.

Two coats of paint, thinner each time. And because perceived density depends on cross-sectional area, halving a shaft's diameter removes roughly three-quarters of its visual bulk. This is the arithmetic behind the most common thing patients tell me: I don't seem to be losing that many, but there's so much less hair. Both statements are true simultaneously.

Step 6 — Telogen lengthens, and empty intervals appear

As anagen shortens, the proportion of follicles in telogen rises. Shedding increases — not because more follicles are dying, but because each one is cycling faster and spending relatively more of its life at rest.

And then a subtler thing happens. After a club hair is released, the follicle may sit empty before the next anagen begins — an interval described in the trichology literature as kenogen, with the release event itself termed teloptosis (Rebora & Guarrera, 2004; Guarrera & Rebora, 2005). Kenogen intervals are longer and more frequent in androgenetic alopecia. An empty follicle contributes nothing to density even though it is alive and countable.

Step 7 — Inflammation and fibrosis arrive around the follicle

This is the step that turns a signalling problem into a structural one, and it is the one most consumer content omits entirely.

Perifollicular inflammatory infiltrates are a documented histological finding in male pattern alopecia (Jaworsky et al., 1992), and the concept of microinflammation as a contributor rather than a bystander is well established in the dermatology literature (Mahé et al., 2000). Histological study of peripilar signs — the faint brown rings visible on dermoscopy around some follicular openings — has correlated them with perifollicular inflammatory and fibrotic change (Deloche et al., 2004). And perifollicular fibrosis has been characterised as playing a pathogenetic role in androgenetic alopecia rather than merely accompanying it (Yoo et al., 2006).

Fibrosis is the difference between an instruction problem and an architecture problem. A follicle receiving a poor instruction can, in principle, receive a better one. A follicle whose surrounding connective tissue has been remodelled into a collagenous sleeve has lost the space and the scaffolding a regenerating follicle needs.

Step 8 — The follicular streamer

At the end of the road, the miniaturised follicle involutes and what remains in the dermis is a follicular streamer — also called a stela: a fibrous tract marking where a follicle used to be. On a biopsy this is countable, and it is the histological signature of a follicle that is not coming back (Whiting, 2001).

Lost, Dormant, or Still Cycling: The Only Question That Matters

Patients ask this constantly, in one form or another. It deserves a straight table.

The middle two rows are where the honest and the dishonest parts of this industry separate.

The hopeful evidence is real: Garza and colleagues found that bald scalp in men with androgenetic alopecia retains its hair follicle stem cells, while lacking the CD200-rich, CD34-positive progenitor population downstream of them (Garza et al., 2011). The reservoir is still present. Bald scalp is not empty scalp.

The sobering half of the same finding is equally real: those men's stem cells were present, and their hair was not growing. A retained reservoir with a failed activation step is still a vellus follicle. Presence is not function, and no product on the market — mine included — has been shown to restore that activation step.

And there is no announcement when you cross from one row to the next. Nobody feels the day their perifollicular collagen consolidated. That absence of a signal is the entire clinical argument for acting early, and it is not a sales argument: it is equally an argument for seeing a dermatologist early, having your ferritin and thyroid checked early, and photographing your scalp early.

What Reverses, What Slows, What Does Not

I would rather be the site that tells you this plainly than the one you find out from later.

Cannot be reversed by any cosmetic, supplement, device, or drug:

• A follicle replaced by a fibrous streamer.
• Any follicle destroyed in a scarring (cicatricial) alopecia — lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, discoid lupus. These are inflammatory diseases that destroy the stem-cell reservoir permanently, they are medical conditions requiring a dermatologist, and if you have scalp burning, tenderness, redness, scaling around follicles or shiny areas where follicular openings have disappeared, close this article and make an appointment. No product here is an answer to that.
• Total follicle count. You were born with all the follicles you will have. Nothing adds more.

Can plausibly be influenced, in the miniaturising window:

• Anagen duration and the anagen-to-telogen ratio — the target of every serious intervention in this category.
• The proportion of follicles resting because of a correctable systemic cause: iron deficiency, thyroid disease, severe caloric restriction, post-illness telogen effluvium. Correcting the cause here is not cosmetic and can matter a great deal.
• The inflammatory environment around the follicle. Given the fibrosis literature above, keeping the perifollicular environment quiet is a coherent objective even where the evidence for a specific ingredient is laboratory-level rather than clinical.

Only pharmaceuticals have randomised placebo-controlled evidence for regrowth in pattern hair loss. Topical minoxidil and oral finasteride carry that evidence and their own labelled risks and contraindications; consult the current prescribing information (DailyMed: minoxidil; DailyMed: finasteride) and a physician, not a blog. Finasteride is contraindicated in pregnancy and in women who may become pregnant, which is the entire reason the drug-free question exists for so many of my former patients. MD products are cosmetics and dietary supplements. They are not drugs, they do not do what drugs do, they are not FDA approved, and I will not present them as equivalent to something with a randomised trial behind it. They are drug-free options addressed to the same hair concerns.

The Bottom Line

Miniaturization is the stepwise downgrading of a terminal follicle into a vellus-like one, over successive cycles, in the same follicle — which is why pattern hair loss thins a scalp long before it empties one. The sequence is traceable: androgen reaches a susceptible follicle; the dermal papilla, where the androgen receptor is expressed, changes the paracrine signals it sends, including DKK-1 and TGF-β2 (Kwack et al., 2008; Hibino & Nishiyama, 2004; Inui & Itami, 2011); anagen shortens; papilla cell number falls, so each rebuild is smaller (Whiting, 2001); the fibre narrows, and because perceived density depends on cross-sectional area, a halved diameter costs about three-quarters of the visual bulk; telogen and empty kenogen intervals lengthen (Rebora & Guarrera, 2004); and perifollicular inflammation and fibrosis accumulate around the follicle (Jaworsky et al., 1992; Mahé et al., 2000; Yoo et al., 2006). Bald scalp retains its stem cells but loses the progenitor population that would activate them (Garza et al., 2011) — so dormant and lost are genuinely different states, with fibrosis and the follicular streamer marking the transition. The practical consequence is not complicated: the window is while follicles are still cycling, no cosmetic or supplement reverses a fibrosed or scarred follicle, and any content telling you otherwise is selling you something.

Dr. Susan Lin's Clinical Perspective

"The cruelty of this process is that it is designed to be missed. It removes about ten percent of your visual density a year, in a mirror you look into every day, with a memory that recalibrates as fast as the change arrives. Patients would tell me they had noticed 'in the last few months' and bring a photograph from four years earlier showing it plainly. That is not denial — it is how perception works. So I stopped asking what people had noticed and started asking for two photographs: one from years ago, one from today, same angle, daylight. That comparison finds miniaturization years before the mirror does, and years is what this window is measured in. I would rather send someone to a dermatologist too early than have them reach my products two years after the follicles worth protecting became fibrous tracts."

— Dr. Susan F. Lin, M.D., Physician Formulator, MD HAIR

Mechanism Spotlight: The Follicular Streamer, and What a Biopsy Reads

There is a specific structure that marks the end of this process, and it is worth knowing about because it is the closest thing to a physical answer to is it gone.

Cut a scalp biopsy horizontally rather than vertically and you get a cross-section through every follicle at a chosen depth — the technique Headington established and Whiting developed into a diagnostic method (Headington, 1984; Whiting, 1993). At mid-dermal level you can count follicles, sort them by shaft calibre, and calculate the terminal-to-vellus ratio. In androgenetic alopecia that ratio falls markedly while the total follicular unit count holds up for a long time — which is the histological statement of everything above.

Go deeper into the specimen and something else appears: follicular streamers, also called stelae. These are fibrous tracts left in the dermis beneath a follicle that has retracted upward. Some are ordinary — every telogen follicle leaves a temporary streamer marking the path it will descend again in the next cycle. But in advanced pattern loss, streamers persist beneath follicles that never come back down, and they are found in association with the perifollicular fibrosis described earlier (Whiting, 2001; Yoo et al., 2006).

That is what lost looks like under a microscope: not an absence, but a scar-like tract where a follicle used to travel. It is also why a pathologist can distinguish miniaturization from a scarring alopecia, in which follicles are replaced outright — and why that distinction is a biopsy question rather than a product question.

Recommended Reading

Pillar pages on mdhair.com:

• Hormonal Hair Loss — the pillar this article sits under
• Drug-Free Hair Loss Treatment — The Complete Guide
• The Lilac & Verbascoside Science
• The Clinical Evidence Behind MD HAIR

Related articles in this series:

• Dermal Papilla Cells: The Cells That Decide Your Hair's Future — the command centre where Steps 2 and 4 of this sequence happen
• Beyond Saw Palmetto: The Drug-Free DHT Blockers That Have Evidence — Step 1 of the sequence above, and how to read botanical claims about it
• Female Pattern Hair Loss: What It Is and What Actually Helps — the clinical picture this process produces, and the full options list
• PCOS and Hair Loss — miniaturization under a correctable hormonal driver, which is the best-case version of this article

Our sister site md-factor.com carries the wider MD® line and its customer reviews.

MD HAIR Product Recommendation

Two products, because this article describes two problems in the same follicle — an internal signalling environment and a local scalp environment — and I would rather explain the pairing than pretend one item covers both.

MD Nutri Hair™ — the internal arm. /products/nutri-hair-supplement

Why, stated precisely. The dermal papilla sits millimetres below the surface, wrapped in the follicle's own blood supply. MD Nutri Hair™ carries the standardised lilac verbascoside whose published research was performed on exactly that cell type: in laboratory studies on human dermal papilla cells, verbascoside reduced the release of pro-inflammatory signals including IL-1α, IL-6, IL-1β and TNF-α, and prevented testosterone-induced death of those cells (Wisuitiprot et al., 2022). Given how much of Step 7 above is about inflammation, the anti-inflammatory finding is the one I lead with, and it is the best-evidenced thing anyone can currently say about this molecule.

Those are cell studies, in a dish, using verbascoside sourced from Acanthus rather than from lilac, and the authors state that clinical study is still needed. We make no claim that verbascoside inhibits 5-alpha-reductase — we removed that claim after reading the primary source it was built on and finding it did not support it.

From the label: one capsule daily, adults only. A Proprietary Blend of 300 mg, plus niacinamide 5 mg, vitamin E as alpha tocopheryl acetate 5 mg, D-biotin 0.05 mg; other ingredients flaxseed powder, lignan powder, lilac. Proprietary blend means the individual amounts are not disclosed. That is lawful and it is our weakest transparency answer, and I would rather say so than let you discover it. Per the product label: do not take if you are pregnant or breast feeding.

MD Follicle Energizer — the topical arm. /products/follicle-energizer

Why. Miniaturization plays out in a physical environment — the perifollicular skin where the inflammation and fibrosis of Step 7 develop. A topical is the only arm that reaches that environment directly. The human evidence for our topical system is a 119-day (17-week) study by an independent third-party testing organisation, n = 24, on the two-step system rather than either product alone, self-reported, with no placebo arm, in a split-scalp design where each participant served as their own control. The report's own sentence, in the same paragraph as its results: "The satisfaction rate (concerning the overall efficacy) is not significantly validated." That travels with any figure, every time.

And the boundary. Neither of these products, nor any product I know of, restores a follicle that has become a fibrous streamer or one destroyed by a scarring alopecia. If your scalp is tender, burning, red or scaling, or if follicular openings have disappeared from an area of shiny skin, the right next step is a dermatologist, not a purchase.

Not sure which stage you are at? The MD HAIR Quiz routes several outcomes to a physician and a laboratory panel rather than to any product of ours.

A note on authenticity: genuine MD HAIR™ and MD Nutri Hair™ products are sold only through mdhair.com, md-factor.com, and the official La Cañada Ventures, Inc. stores on Amazon and Walmart.

References

1. Whiting DA. (2001). Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. Journal of the American Academy of Dermatology, 45(3 Suppl), S81–S86. PMID 11511857
2. Whiting DA. (1993). Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. Journal of the American Academy of Dermatology, 28(5 Pt 1), 755–763. PMID 8496421
3. Headington JT. (1984). Transverse microscopic anatomy of the human scalp. Archives of Dermatology, 120(4), 449–456. PMID 6703750
4. Sinclair R, Torkamani N, Jones L. (2015). Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss. F1000Research, 4, 585. PMID 26339482
5. Olsen EA, Messenger AG, Shapiro J, et al. (2005). Evaluation and treatment of male and female pattern hair loss. Journal of the American Academy of Dermatology, 52(2), 301–311. PMID 15692478
6. Inui S, Itami S. (2011). Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla. Journal of Dermatological Science, 61(1), 1–6. PMID 21167691
7. Kwack MH, Sung YK, Chung EJ, et al. (2008). Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. Journal of Investigative Dermatology, 128(2), 262–269. PMID 17657240
8. Hibino T, Nishiyama T. (2004). Role of TGF-beta2 in the human hair cycle. Journal of Dermatological Science, 35(1), 9–18. PMID 15194142
9. Garza LA, Yang CC, Zhao T, et al. (2011). Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. Journal of Clinical Investigation, 121(2), 613–622. PMID 21206086
10. Stenn KS, Paus R. (2001). Controls of hair follicle cycling. Physiological Reviews, 81(1), 449–494. PMID 11152763
11. Jaworsky C, Kligman AM, Murphy GF. (1992). Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. British Journal of Dermatology, 127(3), 239–246. PMID 1390168
12. Mahé YF, Michelet JF, Billoni N, et al. (2000). Androgenetic alopecia and microinflammation. International Journal of Dermatology, 39(8), 576–584. PMID 10971723
13. Deloche C, de Lacharrière O, Misciali C, et al. (2004). Histological features of peripilar signs associated with androgenetic alopecia. Archives of Dermatological Research, 295(10), 422–428. PMID 14758487
14. Yoo HG, Kim JS, Lee SR, et al. (2006). Perifollicular fibrosis: pathogenetic role in androgenetic alopecia. Biological & Pharmaceutical Bulletin, 29(6), 1246–1250. PMID 16755026
15. Rebora A, Guarrera M. (2004). Teloptosis and kenogen: two new concepts in human trichology. Archives of Dermatology, 140(5), 619–620. PMID 15148114
16. Guarrera M, Rebora A. (2005). Kenogen in female androgenetic alopecia: a longitudinal study. Dermatology, 210(1), 18–20. PMID 15604539
17. Sawaya ME, Price VH. (1997). Different levels of 5α-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. Journal of Investigative Dermatology, 109(3), 296–300. PMID 9284093
18. Bayne EK, Flanagan J, Einstein M, et al. (1999). Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. British Journal of Dermatology, 141(3), 481–491. PMID 10583052
19. Randall VA. (2008). Androgens and hair growth. Dermatologic Therapy, 21(5), 314–328. PMID 18844710
20. Wisuitiprot V, Ingkaninan K, Chakkavittumrong P, et al. (2022). Effects of Acanthus ebracteatus Vahl. extract and verbascoside on human dermal papilla and murine macrophage. Scientific Reports, 12(1), 1491. PMID 35087085 · open access
21. U.S. National Library of Medicine, DailyMed — minoxidil topical labelling
22. U.S. National Library of Medicine, DailyMed — finasteride labelling, including the pregnancy contraindication and handling warning
23. Spincontrol North America, 119-day (17-week) study of the MD® two-step topical system, n = 24, split-scalp design, self-reported outcomes, no placebo arm. Internal report, study on file.
24. MD Nutri Hair™ box artwork, June 2016 — Supplement Facts panel, Other Ingredients and label warnings, as quoted. Internal document, on file.

Dr. Susan F. Lin, M.D. is the physician formulator behind MD HAIR and MD Nutri Hair™, product lines of La Cañada Ventures, Inc. — physician-formulated since 2008 under the MD® mark (U.S. Reg. No. 4,471,494). She trained at Boston University School of Medicine and is board-certified in Obstetrics & Gynecology and in Anti-Aging Medicine (A4M).

This article is for educational purposes and does not constitute medical advice. Scalp pain, burning, redness, scaling around follicles, or areas of shiny skin where follicular openings have disappeared may indicate a scarring alopecia and require prompt evaluation by a dermatologist. Consult your own physician for personalized guidance, and do not start, stop, or change any medication without consulting your prescriber.

MD® products are cosmetics and dietary supplements manufactured in FDA-registered, GMP-compliant facilities. "FDA-registered" describes the facility, never the product: no MD product is FDA approved, and no cosmetic or dietary supplement is. Individual results vary. MD Nutri Hair™ is a dietary supplement. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

MD Nutri Hair™ is for adults only, one capsule daily. Per the product label: do not take if you are pregnant or breast feeding. Because there are no clinical data in pregnant or breastfeeding women, we do not advocate using MD HAIR products during pregnancy or lactation.

Laboratory findings described in this article were obtained in cell culture. They are not clinical outcomes and are not presented as such.

Explore more in the Verbascoside & Lilac Science series at mdhair.com/pages/lilac-verbascoside-science