Pathophysiology of Androgenic Alopecia
Androgenic alopecia results from the progressive miniaturization of genetically susceptible hair follicles mediated by dihydrotestosterone (DHT), which binds to androgen receptors and triggers gradual transformation of terminal follicles into miniaturized follicles. 1, 2
Core Pathophysiologic Mechanism
DHT is the primary mediator - The enzyme 5-alpha-reductase converts testosterone to dihydrotestosterone (DHT) in genetically susceptible hair follicles 1, 3, 2
Androgen receptor activation drives miniaturization - DHT binds to androgen receptors in susceptible follicles, and this hormone-receptor complex activates genes responsible for progressive follicle miniaturization 2
Regional enzyme differences explain the pattern - Young adults with androgenic alopecia have higher levels of 5-alpha-reductase and androgen receptors in frontal hair follicles compared to occipital follicles, explaining why hair loss follows a characteristic pattern 2
Sex-Specific Differences in Pathophysiology
Women have protective aromatase enzyme - Women with androgenic alopecia have much higher levels of cytochrome p-450 aromatase in frontal follicles than men (who have minimal aromatase), and even higher aromatase levels in occipital follicles, which partially protects against DHT effects and explains the diffuse thinning pattern rather than complete baldness 2
Polygenic inheritance affects both sexes equally - The inheritance pattern is polygenic with the same incidence in men and women, typically beginning between ages 12-40 years 2
Progressive Follicular Changes
Three-stage miniaturization process - Hair follicles undergo progressive reduction in diameter, length, and pigmentation over successive growth cycles 4
Anagen phase shortening - DHT causes shortening of successive anagen (growth) cycles, resulting in progressively shorter and finer hairs 1
Tissue remodeling accompanies miniaturization - DHT acts as a co-mediator of dermal sheath thickening, perifollicular fibrosis, and calcification, which restrict follicle growth space, oxygen, and nutrient supply, contributing to the slow, persistent miniaturization 5
Clinical Pattern Development
Male pattern - Bitemporal recession of the frontal hairline followed by diffuse thinning at the vertex results from androgen sensitivity in these specific regions 4
Female pattern (Ludwig pattern) - Diffuse thinning of the crown region with maintenance of the frontal hairline occurs due to protective aromatase activity and different androgen receptor distribution 2, 4
Important Pathophysiologic Considerations
Hyperandrogenism is not required in most cases - Most women with androgenic alopecia have normal menses, pregnancies, and normal androgen levels, indicating that follicular hypersensitivity to normal androgen levels drives the process 2
Endocrine evaluation is selective - Extensive hormonal testing is unnecessary unless signs of androgen excess are present (hirsutism, severe cystic acne, virilization, or galactorrhea), as the pathology is primarily follicular sensitivity rather than systemic androgen excess 6, 2
Progressive and irreversible without treatment - Androgenic alopecia is a chronic progressive disease that worsens over time, and even castration (which decreases androgen production by 95%) stops progression but does not fully reverse established miniaturization, indicating that tissue remodeling becomes self-perpetuating 3, 5