Conflicting Reports Regarding the Histopathological Features of Androgenic Alopecia: Are Biopsy Location, Hair Diameter Diversity, and Relative Hair Follicle Miniaturization Partly to Blame?

Figures & data

Table 1 A Summary of Investigations Reporting Inflammation and/or Fibrosis in AGA Biopsies

Author (Year)	Subjects				Biopsy Methodologies	Balding Subjects		Control Subjects
	Number	Age (Years)	Sex	Hamilton-Norwood/Ludwig Gradient		Inflammation (%)	Fibrosis (%)	Inflammation (%)	Fibrosis (%)
Lattanand & Johnson (1975)^Citation4	23 (347 specimens)	21–48	Male	Not specified	Biopsies from hair transplants	50%	NE	NE; no control group
Kligman (1988)^Citation5	13	21–48	Male	7 with early AGA; 6 with late AGA	Transverse and vertical	NE; early AGA: inflammation in the infundibulum, sebaceous gland, and follicular streamers; late AGA: inflammation still present	NE; early AGA: collagen bundles and fibroblasts noted in follicular streamers; late AGA: fibrosis more evident in follicular streamers with some becoming fibrous tracts	NE; inflammation absent in specimens derived from senescent balding scalps; sparse, mild inflammation noted in normal scalps.	NE
Abell (1988)^Citation6	603	Not specified	600 male, 3 female	Not specified	3–6mm punch biopsy; transverse	77%	25%	NE; no control group
Sperling & Winton (1990)^Citation7	5	Not specified	Male	Not specified	3.5mm punch biopsy; transverse and vertical	100%	NE; increased dermal collagen surrounding follicular groups	NE; no control group
Jaworsky et al (1992)^Citation8	4	25–67 years	3 males, 1 female	Segmented samples by location: samples were obtained from the most affected region, transitional region (perimeter of affected pattern regions), and non-alopecic regions	Not specified	NE; significant inflammation in the infundibulum of specimens derived from transitional scalp	NE; balding samples: mature collagen noted in adventitial sheath; transitional samples: collagen noted in adventitial sheath, but less pronounced	NE; inflammation and fibrous tract remnants scarce among non-alopecic regions
Whiting (1993)^Citation2	106	16–70, average 37 years	Male	Not specified	4mm punch biopsy; horizontal and vertical	70% (inflammation and fibrosis grouped together)		40.9% (inflammation and fibrosis grouped together)
Whiting (1996)^Citation3	412	15–80, average 40 years	193 male, 219 female	Not specified	4mm punch biopsy; horizontal and vertical	71.4% (inflammation and fibrosis grouped together); moderate inflammation and/or fibrosis found in 37%		40% (inflammation and fibrosis grouped together); moderate inflammation and/or fibrosis found in 11%
Deloche et al (2004)^Citation9	40	19–51 in male group, 21–65 in female group	21 male, 19 female	Norwood I: 2 Norwood II: 10 Norwood III: 3 Norwood IV: 5 Norwood VI: 1 Ludwig I: 4 Ludwig II: 12 Ludwig III: 3	One 4mm punch biopsy, one 2mm punch biopsy; horizontal and vertical	100% in males, 100% in females	62% of males, 51% of females	NE; no control group
Won et al (2008)^Citation10	10	20–35	Male	Norwood III to Norwood IV, specimens were taken from both balding vertex and non-balding occipital region	4mm punch biopsy; horizontal	NE; significantly increased numbers of mast cells	NE; significantly increased collagen bundles and elastic fibers in vertex samples correlated with higher mast cells	NE; collagen and/or elastic fiber deposition absent in non-balding occipital samples
El-Domyati et al (2009)^Citation11	40	20–80	Male	Norwood I: 3 Norwood II: 4 Norwood IIa: 3 Norwood III: 1 Norwood IIIa: 1 Norwood IIIv: 5 Norwood IV: 3 Norwood IVa: 3 Norwood V: 5 Norwood Va: 2 Norwood VI: 8 Norwood VII: 2	4mm punch biopsy; biopsies taken from balding area, non-balding occipital area, and frontal area from control subjects; horizontal and transverse	90%	60%	17.5%
Aslani et al (2018)^Citation12	61	11–50 years in the female group, 18–37 in the male group	46 female, 15 male	Not specified	4mm punch biopsy; horizontal, vertical, and transverse	66.7% of males, 35.7% of females	NE	NE; no control group
Tandon et al (2019)^Citation13	30	28–45 years	Female	Not specified	4mm punch biopsy	56%	30%	NE; no control group
Goyal et al (2019)^Citation14	9	26–30 in men, 25–48 in women	5 male, 4 female	Norwood II: 1 Norwood IV: 2 Norwood VI: 2 Ludwig I: 2 Ludwig II: 2	4mm punch biopsies; transverse	0% in males, 0% in females	0% in males, 25% in females	NE; no control group
Valdebran et al (2020)^Citation15	37	Not specified	Not specified	Not specified	Examined specimens with at least one vertical section	73%	68%	84%	82%

Abbreviation: NE, not estimated.

Figure 1 A photograph of a male vertex in the early stages of AGA. Zones represent potential biopsy locations separated by approximately 1 mm. Zone A features relatively high hair counts, low HDD, and terminal hair follicles skewed toward earlier cycles of HFM. Zone B features relatively low hair counts, high HDD, and terminal hair follicles skewed toward later cycles of HFM.

Abbreviations: AGA, androgenic alopecia; HDD, hair diameter diversity; HFM, hair follicle miniaturization.

Figure 2 A proposed classification system to quantify relative HFM within the same subject. (A) Class 0 represents full-thickness hairs unaffected by AGA. (B–F) Classes 1–5 represent AGA-affected hairs benchmarked to Class 0, with miniaturization segmented by 20% increments per class.

Abbreviations: HFM, hair follicle miniaturization; AGA, androgenic alopecia.

Figure 3 A hypothetical model showing a dynamic relationship between AGA and the presence of inflammation, fibrosis, and prostaglandin activity based on relative HFM. Inflammation is denoted by red markings; PGE₂ synthase is denoted by green markings; PGD₂ and PGJ₂ are denoted by purple markings; fibrosis is denoted by blue perifollicular shading. (A) Class 0 hair follicles unaffected by AGA show no fibrosis and relatively low levels of inflammation, PGE₂ synthase, PGD₂, and PGJ₂. (B and C): Class 1–2 hair follicles in the early stages of HFM show relatively low levels of fibrosis but increased inflammation, PGE₂ synthase, PGD₂, and PGJ₂. (D–F) Class 3–5 hair follicles in the mid- to late-stages of HFM show increasing levels of fibrosis, decreased activity of PGE₂ synthase, and sustained levels of PGD₂ and PGJ_2.

Abbreviations: AGA, androgenic alopecia; HFM, hair follicle miniaturization; PGE₂, Prostaglandin E₂; PGD₂, Prostaglandin D₂; PGJ₂, Prostaglandin J₂.

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