Understanding Hair Biology: How Hair Grows and Why Hair Loss Occurs

Table of Contents

• Introduction: Why Hair Matters
• Glossary of Hair Terms
• Structure and Function of Hair Follicles
• How Hair Follicles Develop
• The Hair Growth Cycle: Anagen, Catagen, and Telogen
• Hormonal and Neural Control of Hair Growth
• Understanding Hair Growth Disorders
• Current Treatments and Future Possibilities
• Source Information

Introduction: Why Hair Matters

Hair serves multiple biological functions including protection from environmental elements and dispersion of sweat gland products. Beyond its physical purposes, hair holds significant psychosocial importance in our society. Patients experiencing hair loss (alopecia) or excessive hair growth often suffer tremendously emotionally.

The demand for effective hair growth medications has created a multibillion-dollar industry, yet few truly effective drugs are available. Recent advances in understanding hair follicle biology and pathology are paving the way for more effective future treatments for hair growth disorders.

Glossary of Hair Terms

Understanding these medical terms is essential for discussing hair conditions:

• Alopecia: Abnormal hair loss
• Androgenetic alopecia: Pattern baldness caused by miniaturization of genetically predisposed follicles
• Alopecia areata: Patchy hair loss thought to be caused by autoimmune response
• Permanent alopecia: Hair loss caused by destruction of hair follicles
• Anagen: Active growth stage of hair cycle
• Anagen effluvium: Abrupt shedding from interruption of active growth (e.g., chemotherapy)
• Bulb: Lowermost portion containing rapidly proliferating matrix cells
• Bulge: Area containing epithelial stem cells responsible for regenerating follicles
• Catagen: Regression and involution stage
• Club hair: Fully keratinized, dead hair product of telogen stage
• Hirsutism: Excessive hair growth in androgen-dependent areas in women
• Hypertrichosis: Excessive diffuse hair growth beyond normal patterns
• Miniaturization: Primary process in androgenetic alopecia converting large terminal hairs to small vellus hairs
• Telogen: Resting stage of hair cycle
• Telogen effluvium: Excessive shedding from increased follicles entering telogen
• Terminal hair: Large, pigmented hairs on scalp and body
• Vellus hair: Short, nonpigmented hairs found on face and bald scalp

Structure and Function of Hair Follicles

Hair follicles vary in size and shape depending on their location but share the same basic structure. Rapidly proliferating matrix cells in the hair bulb produce the hair shaft, whose bulk—the cortex—is composed of hair-specific intermediate filaments and associated proteins.

Melanocytes interspersed among the matrix cells produce pigment in the hair shaft. As matrix cells differentiate and move upward, they are compressed into their final shape by the rigid inner-root sheath, whose dimensions largely determine hair shape.

The dermal papilla, composed of specialized fibroblasts at the follicle base, controls the number of matrix cells and thus hair size. Normal development and cycling depend on interactions between follicular epithelium and the mesenchymal dermal papilla.

The bulge region contains epithelial stem cells—the slowest-cycling and longest-lived epithelial cells within hair follicles. These cells may also serve as a reservoir for epidermal and sebaceous-gland cells, migrating out to regenerate epidermis after injury.

Hair follicles contain multiple cell types including melanocytes, Langerhans' cells (dendritic antigen-presenting cells), and Merkel cells (specialized neurosecretory cells). The follicle acts as a sensory organ and immunologic sentinel, detecting mechanical stimuli and surface pathogens.

How Hair Follicles Develop

During fetal development, epithelium and underlying mesenchyme interact to form hair follicles. The precise distribution of approximately 5 million hair follicles over the human body is established in utero, determining future hair phenotypes.

No additional follicles form after birth, although follicle size can change under hormonal influences. The spacing and distribution are established by genes expressed early in morphogenesis, including lymphoid-enhancer factor 1, bone morphogenetic protein 4, and transforming growth factor β type II receptor.

Later in development, cells containing homeobox gene products appear precisely where follicles will form. Morphogens like sonic hedgehog and wnt, with intracellular signaling molecules like β-catenin and lymphoid-enhancer factor 1, influence maturation of new hair follicles.

The Hair Growth Cycle: Anagen, Catagen, and Telogen

Each hair follicle perpetually cycles through three stages: growth (anagen), involution (catagen), and rest (telogen). Understanding the signals that control these transitions is crucial for developing hair treatments.

Anagen Stage (Growth)

The onset of anagen recapitulates hair-follicle development, beginning with proliferation of secondary germ cells in the bulge. Interactions between dermal papilla and overlying epithelium are critical. Insulin-like growth factor 1 and fibroblast growth factor 7, produced by dermal papilla, play important roles in maintaining follicle growth.

Hair length is proportional to anagen duration. Scalp follicles remain in anagen for 2-8 years producing long hairs, while eyebrow follicles only last 2-3 months producing short hairs. The cessation of anagen is controlled by fibroblast growth factor 5, with epidermal growth factor receptors also influencing this transition.

Catagen Stage (Involution)

During catagen, follicles undergo controlled involution reflecting programmed cell death (apoptosis) in follicular keratinocytes. Follicular melanogenesis ceases, and some melanocytes undergo apoptosis. The dermal papilla condenses and moves upward to rest underneath the bulge.

If the dermal papilla fails to reach the bulge, the follicle stops cycling permanently, as seen in mutations of the hairless gene. Some follicles are destroyed by inflammatory-cell infiltrate in "programmed organ deletion," which may account for certain permanent alopecias.

Telogen Stage (Rest)

During telogen, the hair shaft matures into a club hair, eventually shed during combing or washing. Most people lose 50-150 scalp hairs daily. Telogen typically lasts 2-3 months before follicles reenter anagen.

The percentage of follicles in telogen varies by body region: 5-15% of scalp follicles versus 40-50% of trunk follicles. Increased telogen percentage leads to excessive shedding, making drugs that maintain or reduce this percentage valuable for treating hair loss.

Hormonal and Neural Control of Hair Growth

Multiple hormones modulate hair growth including estrogens, thyroid hormones, glucocorticoids, retinoids, prolactin, and growth hormone. Androgens have the most dramatic effects through androgen receptors in the dermal papilla.

Testosterone and dihydrotestosterone increase follicle size in androgen-dependent areas like the beard during adolescence, but later cause miniaturization in scalp follicles (androgenetic alopecia). Follicles in balding skin differ in androgen metabolism, androgen receptor numbers, and secretory responses.

Skin cells contain both isoenzymes of 5α-reductase (types I and II) that convert testosterone to more potent dihydrotestosterone. Type II is found in hair follicles, and its inhibition by finasteride slows androgenetic alopecia progression.

Hair follicles are richly innervated, with constant nerve remodeling throughout the hair cycle. The bulge region is especially rich in nerve endings and Merkel cells that may control follicle proliferation through neurotrophins and neuropeptides.

Understanding Hair Growth Disorders

Except for rare congenital defects and scarring alopecias, most hair loss and unwanted growth reflect aberrations of hair-follicle cycling and are theoretically reversible.

Telogen effluvium—transient shedding associated with drugs, fever, endocrine abnormalities, childbirth, anemia, and malnutrition—occurs when increased follicles prematurely enter telogen. This typically begins 2-4 months after the inciting event and lasts several months, with regrowth usually following.

Androgenetic alopecia involves progressive shortening of successive anagen cycles alongside gradual miniaturization of genetically predisposed follicles in the presence of androgens. Large terminal hairs are replaced by barely visible vellus hairs, though follicles continue cycling, making this condition potentially reversible.

Hirsutism and hypertrichosis result from extended anagen stage with abnormal follicle enlargement, transforming vellus hairs into terminal hairs. Inflammation around the bulge area in conditions like graft-versus-host disease and androgenetic alopecia may damage follicle stem cells, decreasing hair density.

Current Treatments and Future Possibilities

Two FDA-approved drugs treat androgenetic alopecia: topical minoxidil solution and oral finasteride. Minoxidil prolongs anagen, causes resting follicles to grow, and enlarges follicles, though its exact mechanism remains unknown and effects vary significantly between patients.

Finasteride blocks 5α-reductase type II, decreasing both serum and cutaneous dihydrotestosterone concentrations to inhibit androgen-dependent miniaturization. However, simply removing androgens doesn't typically reverse miniaturization, making current treatments often ineffective for advanced cases.

Since dermal papilla volume determines hair shaft diameter and possibly anagen duration, abnormalities here may underlie androgenetic alopecia. Future treatments targeting these fundamental mechanisms hold promise for more effective hair restoration.

Source Information

Original Article Title: The Biology of Hair Follicles.
Authors: Ralf Paus, M.D., and George Cotsarelis, M.D.
Publication: The New England Journal of Medicine, Volume 341 Number 7, August 12, 2004
Note: This patient-friendly article is based on peer-reviewed research from the Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Germany and the Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia.