Androgenic alopecia

Androgenic alopecia
Classification and external resources
Androgenic alopecia in a male
ICD-10	L64
DiseasesDB	7773
eMedicine	derm/21
MeSH	D000505

Androgenic alopecia (also known as androgenetic alopecia or alopecia androgenetica) is the most common cause of hair loss and thinning in humans. Variants appear in both men and women. Androgenic alopecia also occurs in chimpanzees, and orangutans.^[1] In humans, this condition is also commonly known as male pattern baldness. In classic pattern baldness, hair is lost in a well-defined pattern, beginning above both temples. Hair also thins at the crown of the head. Often a rim of hair around the sides and rear of the head is left. This type of pattern is dubbed "Hippocratic balding" and may rarely progress to complete baldness. Women do not suffer classic male pattern baldness, instead the hair becomes thinner around the whole scalp, and the hairline does not recede. This is dubbed "female pattern baldness" and may occur in males. This variety of androgenic alopecia in women rarely leads to total baldness.

Cause

A variety of genetic (and possibly environmental) factors apparently play a role in androgenic alopecia. Although researchers have long studied the factors that may contribute to this condition, many remain unknown. Minimally, pattern hair loss is related to hormones called androgens, particularly dihydrotestosterone (DHT). Androgens are important for normal male sexual development before birth and during puberty. Androgens also have other important functions in both males and females, such as regulating hair growth and sex drive.

Male pattern baldness is caused by a genetic sensitivity of hair follicles to DHT. This hormone causes follicles to shrink or "miniaturize". In turn, this shortens their lifespan and prevents them from producing hair normally.^[2]

Recently the existing theories have been challenged on the ground that while the androgens in question are responsible for hair growth on the face and all over the body of men, hair loss only occurrs at the top of the scalp. For example, it has been suggested that androgenic alopecia is a consequence of the anabolic effect of androgens such as hormonal changes leading to structural changes in skin and scalp which in turn cause hair loss.^[3]

Hair loss and genetics

Much research concerns the genetic component of male pattern baldness, or androgenic alopecia (AGA). Research indicates that susceptibility to premature male pattern baldness is largely X-linked, which means it is linked to genes on an X-chromosome. Other genes that are not sex linked are also involved, however. Men whose fathers had experienced hairloss were 2.5 times more likely to experience hairloss themselves, regardless of the mother's side of the family.^[4][5]

Large studies in 2005 and 2007 stress the importance of the maternal line in the inheritance of male pattern baldness. German researchers name the androgen receptor gene as a necessary condition for balding.^[6] They conclude that a specific variant of the androgen receptor is needed for AGA to develop. This study has been confirmed by other researchers.^[7] This gene is recessive. Thus, a female would need two X chromosomes with the defect to show typical male pattern alopecia. Since androgens and their interaction with the androgen receptor are the cause of AGA, the androgen receptor gene plays an important part in its development.

Other research in 2007 suggests another gene on the X chromosome, that lies close to the androgen receptor gene, is an important gene in male pattern baldness. Researchers^[who?] found the region Xq11-q12 on the X-chromosome to be strongly associated with AGA in males. They point at the EDA2R gene as the gene that is mostly associated with AGA.^[8]

Other genes involved with hair loss have been found, one of them being an allele on chromosome 3. The allele is located at 3q26.^[9] This allele is recessive.

There are also genes that are involved in hair loss, although not male pattern baldness per se. In particular, three genes have been shown to both affect hair texture and also cause baldness in some people. One of these is P2RY5. Mutations in this gene affects hair structure "woolly hair".^[10] Certain variants can lead to baldness.^[11]

In May 2009, researchers in Japan identified a gene, SOX21, a Y-linked gene that may be be responsible for some hair loss conditions in humans.^[12]

Hormone levels correlated with androgenic alopecia

Men with androgenic alopecia typically have higher levels of 5-alpha-reductase, lower levels of total testosterone, higher levels of unbound/free testosterone, and higher levels of total free androgens including DHT.^[13][14]

5-alpha-reductase is responsible for converting free testosterone into DHT. The genes for 5-alpha-reductase are known.^[15] The enzymes are present predominantly in the scalp and prostate. Levels of 5-alpha-reductase are one factor in determining levels of DHT in the scalp. Drugs which interfere with 5-alpha-reductase (such as finasteride, which inhibits the predominant type 2 isoform) have been approved by the FDA as treatments for hair loss.

Sex hormone binding globulin (SHBG), which is responsible for binding testosterone and preventing its bioavailability and conversion to DHT, is typically lower in individuals with high DHT. SHBG is downregulated by insulin.

Increased levels of Insulin Growth Factor-1 (IGF-1) have been correlated to vertex balding.^[16]

High insulin levels seem the likely link between metabolic syndrome and baldness. Low levels of SHBG in men and non-pregnant women are also correlated with glucose intolerance and diabetes risk, though this correlation disappears during pregnancy.^[17]

Hair loss and lifestyle

While genetic factors seem to play the principal role in the development and progression of androgenic alopecia, lifestyle also plays a minor role as demonstrated by the vast increase in male and female pattern baldness in Japan after World War II. Pattern baldness (androgenic alopecia) was either rare or non-existent among hunter-gatherer societies.^[18]

One study did show that free testosterone is lower 24 hours after intense aerobic exercise in men who already have high endurance^[19] but it was not investigated whether that level remains lowered beyond that point, or whether that lowering affects male pattern baldness in any way. It has been suggested^{[citation needed]} that weight training may have a detrimental effect on hair by increasing testosterone levels; however, there is at least one study that indicates a decline in free testosterone as a result of weight training.^[20]

Theories on male pattern baldness

One debatable theory, advanced by Muscarella and Cunningham, suggests baldness came about in males through sexual selection as an enhanced signal of aging and social maturity, whereby aggression and risk-taking decrease and nurturing behaviours increase. This may have conveyed a male with enhanced social status but reduced physical threat, which could enhance ability to secure reproductive partners and raise offspring to adulthood.

In a study by Muscarella and Cunnhingham,^[21] males and females viewed six male models with different levels of facial hair (beard and mustache or none) and cranial hair (full head of hair, receding and bald). Participants rated each combination on 32 adjectives related to social perceptions. Males with facial hair and those with bald or receding hair were rated as being older than those who were clean shaven or had a full head of hair. Beards and a full head of hair were seen as being more aggressive and less socially mature, and baldness was associated with more social maturity. A review of social perceptions of male pattern baldness has been provided by Henss (2001).^{[citation needed]}

The assertion that male pattern baldness is intended to convey a social message is supported by the fact that pattern baldness is common in other primates and is often used to convey increased status and maturity. Gorillas have anatomically enlarged foreheads for this reason.^{[citation needed]} This suggests that baldness may have happened to enhance the apparent size of the forehead and increase the area of the face to be displayed.

It should also be noted that most ancestral primates had a shorter life-span, so there was no significant baldness in the society. As the life expectancy continuously increases, baldness remains uneliminated.

Other hypotheses include genetic linkage to beneficial traits unrelated to hair loss and genetic drift.

Diagnosis

The diagnosis of androgenic alopecia can be usually established based on clinical presentation in men. In women, the diagnosis usually requires more complex diagnostic evaluation.

Differential diagnosis involves eliminating other causes of hair loss (such as poisoning) and comparing the pattern of hair loss to a typical male pattern baldness progression.^[22]

In most cases androgenic alopecia may be confirmed by trichoscopy.^[23]

It can be hard to know the diagnosis for sure without a biopsy.^[24]

Treatments

Main article: Management of baldness

While many people with male pattern baldness choose to accept the condition as they accepted their hair color or shape, there are baldness treatments which can manage and reduce or halt hair loss.

Regrowth of lost hair in the early stages of male pattern baldness can be fully restored with treatment. However, bald spots where hair follicles have been destroyed cannot be restored with non-invasive treatments and require a hair transplant to achieve coverage.^[25]

See also

• Dihydrotestosterone
• Noncicatricial alopecia
• Management of baldness
• Ludwig scale - The scale which rates the severity of androgenic alopecia in females
• Hamilton-Norwood scale - The scale which rates the severity of androgenic alopecia in males

References

1. ^ "The latest on baldness cures". Health News. December 1994. Archived from the original on August 1, 2008. http://web.archive.org/web/20080801031525/http://findarticles.com/p/articles/mi_m0857/is_n6_v12/ai_16395133. Retrieved 2010-11-28. 
2. ^ Help for Hair Loss: Men's Hair Loss – Causes. Webmd.com (2010-03-01). Retrieved on 2010-11-28.
3. ^ Soni, V.K. (2009). "Androgenic alopecia: A counterproductive outcome of the anabolic effect of androgens". Medical Hypotheses 73 (3): 420–426. doi:10.1016/j.mehy.2009.03.032. PMID 19477078. 
4. ^ Chumlea W, Rhodes T, Girman C, Johnson-Levonas A, Lilly F, Wu R, Guo S (2004). "Family history and risk of hair loss.". Dermatology 209 (1): 33–9. doi:10.1159/000078584. PMID 15237265. 
5. ^ Genetics of Pattern Baldness
6. ^ Hillmer, AM; Hanneken, S; Ritzmann, S; Becker, T; Freudenberg, J; Brockschmidt, FF; Flaquer, A; Freudenberg-Hua, Y et al. (2005). "Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia". American journal of human genetics 77 (1): 140–148. doi:10.1086/431425. PMC 1226186. PMID 15902657. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226186. 
7. ^ Levy-Nissenbaum, E; Bar-Natan, M; Frydman, M; Pras, E (2005). "Confirmation of the association between male pattern baldness and the androgen receptor gene". European journal of dermatology 15 (5): 339–340. PMID 16172040. 
8. ^ http://www.nature.com/jid/journal/v128/n9/full/jid200860a.html
9. ^ Hillmer, Axel M.; Flaquer, Antonia; Hanneken, Sandra; Eigelshoven, Sibylle; Kortüm, Anne-Katrin; Brockschmidt, Felix F.; Golla, Astrid; Metzen, Christine et al. (2008). "Genome-wide Scan and Fine-Mapping Linkage Study of Androgenetic Alopecia Reveals a Locus on Chromosome 3q26". The American Journal of Human Genetics 82 (3): 737–743. doi:10.1016/j.ajhg.2007.11.014. 
10. ^ Shimomura, Yutaka; Wajid, Muhammad; Ishii, Yoshiyuki; Shapiro, Lawrence; Petukhova, Lynn; Gordon, Derek; Christiano, Angela M (2008). "Disruption of P2RY5, an orphan G protein–coupled receptor, underlies autosomal recessive woolly hair". Nature Genetics 40 (3): 335–339. doi:10.1038/ng.100. PMID 18297072. 
11. ^ Petukhova, L; Sousajr, E; Martinezmir, A; Vitebsky, A; Dossantos, L; Shapiro, L; Haynes, C; Gordon, D et al. (2008). "Genome-wide linkage analysis of an autosomal recessive hypotrichosis identifies a novel P2RY5 mutation". Genomics 92 (5): 273–278. doi:10.1016/j.ygeno.2008.06.009. PMID 18692127. 
12. ^ "Scientists identify gene that may explain hair loss". Reuters. 2009-05-25. http://uk.reuters.com/article/scienceNews/idUKTRE54O4D020090525. 
13. ^ Stárka, L; Cermáková, I; Dusková, M; Hill, M; Dolezal, M; Polácek, V (2004). "Hormonal Profile of Men with Premature Balding". Experimental and Clinical Endocrinology & Diabetes 112 (1): 24–8. doi:10.1055/s-2004-815723. PMID 14758568. 
14. ^ Denmark-Wahnefried, Wendy; Lesko, Samuel M.; Conaway, Mark R.; Robertson, Cary N.; Clark, Richard V.; Lobaugh, Bruce; Mathias, Barbara J.; Strigo, Tara Smith et al. (1997). "Serum androgens: associations with prostate cancer risk and hair patterning". Journal of Andrology 18 (5): 495–500. PMID 9349747. http://www.andrologyjournal.org/cgi/pmidlookup?view=long&pmid=9349747. 
15. ^ Ellis, Justine A.; Panagiotopoulos, Sianna; Akdeniz, Aysel; Jerums, George; Harrap, Stephen B. (2005). "Androgenic correlates of genetic variation in the gene encoding 5α-reductase type 1". Journal of Human Genetics 50 (10): 534–537. doi:10.1007/s10038-005-0289-x. PMID 16155734. 
16. ^ Signorelloa, L; Wuub, J; Hsiehb, C; Tzonouc, A; Trichopoulosa, D; Mantzorosd, C (1999). "Hormones and hair patterning in men: A role for insulin-like growth factor 1?". Journal of the American Academy of Dermatology 40 (2 Pt 1): 200–203. doi:10.1016/S0190-9622(99)70188-X. PMID 10025745. 
17. ^ McElduff, A.; Hitchman, R.; McElduff, P. (2006). "Is sex hormone-binding globulin associated with glucose tolerance?". Diabetic Medicine 23 (3): 306–312. doi:10.1111/j.1464-5491.2005.01780.x. PMID 16492215. 
18. ^ Cordain, L; Eades, MR; Eades, MD (2003). "Hyperinsulinemic diseases of civilization: more than just Syndrome X". Comparative Biochemistry and Physiology – Part A: Molecular & Integrative Physiology 136 (1): 95–112. doi:10.1016/S1095-6433(03)00011-4. PMID 14527633. 
19. ^ Daly, W.; Seegers, C. A.; Rubin, D. A.; Dobridge, J. D.; Hackney, A. C. (2004). "Relationship between stress hormones and testosterone with prolonged endurance exercise". European Journal of Applied Physiology 93 (4): 375–380. doi:10.1007/s00421-004-1223-1. PMID 15618989. 
20. ^ Ara, I.; Perez-Gomez, J.; Vicente-Rodriguez, G.; Chavarren, J.; Dorado, C.; Calbet, J. A. L. (2007). "Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme". British Journal of Nutrition 96 (6): 1053–1059. doi:10.1017/BJN20061956. PMID 17181880. 
21. ^ Muscarella, F. & Cunningham, M.R. (1996). "The evolutionary significance and social perception of male pattern baldness and facial hair". Ethology and Sociobiology 17 (2): 99–117. doi:10.1016/0162-3095(95)00130-1. 
22. ^ Diagnosing Men's Hair Loss: Norwood Scale Chart. Webmd.com (2010-03-01). Retrieved on 2010-11-28.
23. ^ Rudnicka L, Olszewska M, Rakowska A, Kowalska-Oledzka E, Slowinska M. (2008). "Trichoscopy: a new method for diagnosing hair loss". J Drugs Dermatol 7 (7): 651–654. PMID 18664157. 
24. ^ Rashid, RM; Thomas, V (2010). "Androgenic pattern presentation of scarring and inflammatory alopecia". Journal of the European Academy of Dermatology and Venereology 24 (8): 979–980. doi:10.1111/j.1468-3083.2009.03557.x. PMID 20059630. 
25. ^ Propecia (Finasteride) Drug Information: User Reviews, Side Effects, Drug Interactions and Dosage at RxList. Rxlist.com (2010-04-13). Retrieved on 2010-11-28.

External links

• NLM- Genetics Home Reference
• Scow, Dean Thomas; Nolte, Robert S.; Shaugnessy, Allen F. (April 1999). "Medical treatments for balding in men". American family physician 59 (8): 2189–2194, 2196. PMID 10221304. http://www.aafp.org/afp/990415ap/2189.html. 
• Kabai, P (2008). "Androgenic alopecia may have came about to protect men from prostate cancer by increasing skin exposure to ultraviolet radiation". Medical Hypotheses 70 (5): 1038–1040. doi:10.1016/j.mehy.2007.07.044. PMID 17910907. 
• How Hair Replacement Works Covers oral medications, hair transplant surgery, and topical treatments.
• [1] Male Pattern Baldness Genetics
• [2] USA Today article examining the impact of baldness on career success.