Male-pattern hair loss

Male-pattern hair loss
Male androgenic alopecia
Classification and external resources
Specialty	Dermatology, plastic surgery
ICD-10	L64
DiseasesDB	7773
MedlinePlus	001177
eMedicine	derm/21
Patient UK	Male-pattern hair loss
MeSH	D000505

Male-pattern hair loss (MPHL), also known as androgenic alopecia and male pattern baldness, is hair loss that occurs due to an underlying susceptibility of hair follicles to shrinkage due to the influence of androgenic hormones. Male-pattern hair loss is the most common cause of hair loss and will affect up to 70% of men and 40% of women at some point in their lifetimes. Men typically present with progressive hair loss at the temples and vertex balding, whereas women typically present with diffuse hair loss over the top of their scalps. Both genetic and environmental factors play a role, and many causes of male-pattern hair loss remain unknown.

Signs and symptoms

Classic male-pattern hair loss begins above the temples and vertex, or calvaria, of the scalp. As it progresses, a rim of hair at the sides and rear of the head remains. This has been referred to as a 'Hippocratic wreath', and rarely progresses to complete baldness. The Hamilton-Norwood scale has been developed to grade androgenic alopecia in males.

Female androgenic alopecia is known colloquially as "female pattern baldness", although its characteristics can also occur in males. It more often causes diffuse thinning without hairline recession; similar to its male counterpart, female androgenic alopecia rarely leads to total hair loss. The Ludwig scale grades severity of androgenic alopecia in females.

Causes

Hormones

Androgens can interact with the Wnt signalling pathway to cause to hair loss.

Research indicates that the initial programming of pilosebaceous units of hair follicles begins in utero. The physiology is primarily androgenic, with dihydrotestosterone (DHT) the major contributor at the dermal papillae. Men with premature androgenic alopecia tend to have lower than normal values of sex hormone-binding globulin, follicle stimulating hormone (FSH), testosterone, and epitestosterone when compared to normal controls. Although follicles were previously thought permanently gone in areas of complete hair loss, they are more likely dormant, as recent studies have shown the scalp contains the stem cell progenitor cells from which the follicles arose.

Transgenic studies have shown that growth and dormancy of hair follicles are related to the activity of insulin-like growth factor (IGF) at the dermal papillae, which is affected by DHT. Androgens are important in male sexual development around birth and at puberty. They regulate sebaceous glands, apocrine hair growth, and libido. With increasing age, androgens stimulate hair growth on the face, but suppress it at the temples and scalp vertex, a condition that has been referred to as the 'androgen paradox'.

Men with androgenic alopecia typically have higher 5-alpha-reductase, lower total testosterone, higher unbound/free testosterone, and higher free androgens, including DHT. 5-alpha-reductase converts free testosterone into DHT, and is highest in the scalp and prostate gland. DHT is most commonly formed at the tissue level by 5α-reduction of testosterone. The genetic corollary that codes for this enzyme has been discovered. Prolactin has also been suggested to have different effects on the hair follicle across gender.

Also, crosstalk occurs between androgens and the Wnt-beta-catenin signaling pathway that leads to hair loss. At the level of the somatic stem cell, androgens promote differentiation of facial hair dermal papillae, but inhibit it at the scalp. Other research suggests the enzyme prostaglandin D2 synthase and its product prostaglandin D2 (PGD2) in hair follicles as contributive.

These observations have led to study at the level of the mesenchymal dermal papillae. Types 1 and 2 5α reductase enzymes are present at pilosebaceous units in papillae of individual hair follicles. They catalyze formation of the androgens testosterone and DHT, which in turn regulate hair growth. Androgens have different effects at different follicles: they stimulate IGF-1 at facial hair, leading to growth, but stimulate TGF β1, TGF β2, dickkopf1, and IL-6 at the scalp, leading to catagenic miniaturization. Hair follicles in anaphase express four different caspases.

Hair follicle and mesenchymal dermal papilla, labelled at top

Genetics

Balding is multifactorial, with several lines of evidence suggesting it most likely functions by a genetic predisposition (diathesis). Since androgens and androgen receptors (AR) are the initiating cause of androgenic alopecia, their genetic corollaries are a subject of much research.

Age

Androgens stimulate growth of facial hair, but can suppress scalp hair, a condition that has been called the 'androgen paradox'.

A number of hormonal changes occur with aging:

1. Decrease in testosterone
2. Decrease in serum DHT and 5-alpha reductase
3. Decrease 3AAG, a peripheral marker of DHT metabolism
4. Increase in SHBG
5. Decrease in androgen receptors, 5-alpha reductase type I and II activity, and aromatase in the scalp

This decrease in androgens and androgen receptors, and the increase in SHBG are opposite the increase in androgenic alopecia with aging. This is not intuitive, as testosterone and its peripheral metabolite, DHT, accelerate hair loss, and SHBG is thought to be protective. The ratio of T/SHBG, DHT/SHBG decreases by as much as 80% by age 80, in numeric parallel to hair loss, and approximates the pharmacology of antiandrogens such as finasteride.

An example of premature age effect is Werner's syndrome, a condition of accelerated aging from low-fidelity copying of mRNA. Affected children display premature androgenic alopecia.

Metabolic syndrome

A number of studies have found a link between androgenic alopecia and metabolic syndrome, suggesting the combination as a male homologue to polycystic ovary syndrome.

Multiple cross-sectional studies have found associations between early androgenic alopecia, insulin resistance, and metabolic syndrome, with low HDL being the component of metabolic syndrome with highest association. Linolenic and linoleic acids, two major dietary sources of HDL, are 5 alpha reductase inhibitors. Premature androgenic alopecia and insulin resistance may be a clinical constellation that represents the male homologue, or phenotype, of polycystic ovary syndrome.

In support of the association, finasteride improves glucose metabolism and decreases glycosylated hemoglobin HbA1c, a surrogate marker for diabetes mellitus. The low SHBG seen with premature androgenic alopecia is also associated with, and likely contributory to, insulin resistance.

Because of its association with metabolic syndrome and altered glucose metabolism, both men and women with early androgenic hair loss should be screened for impaired glucose tolerance and diabetes mellitus II.

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. Further evaluation of the differential requires exclusion of other causes of hair loss, and assessing for the typical progressive hair loss pattern of androgenic alopecia. Trichoscopy can be used for further evaluation. Biopsy may be needed to exclude other causes of hair loss, and histology would demonstrate perifollicular fibrosis.

Management

Main article: Management of hair loss

Medication

Hair loss can be slowed or reversed in its early stages with medication. Medications approved by the United States' Food and Drug Administration (FDA) to treat male-pattern hair loss include minoxidil and finasteride.

Androgen-dependent

Finasteride is a medication of the 5α-reductase inhibitors (5-ARIs) class. By inhibiting type II 5-ARI, finasteride prevents the conversion of testosterone to dihydrotestosterone in various tissues including the scalp. Increased hair on the scalp can be seen within three months of starting finasteride treatment and longer-term studies have demonstrated increased hair on the scalp at 24 and 48 months with continued use. Treatment with finasteride more effectively treats male-pattern hair loss at the vertex than male-pattern hair loss at the front of the head and temples.

Dutasteride is a medication in the same class as finasteride but inhibits both type I and type II 5-alpha reductase. Dutasteride is approved for the treatment of male-pattern hair loss in Korea, but not in the United States. However, it is commonly used off-label to treat male-pattern hair loss.

Androgen-independent

Minoxidil is a growth stimulant that stimulates already-damaged hair follicles to produce normal hair. Minoxidil does not, however, provide any protection to the follicles from further DHT damage, and when a follicle eventually becomes completely destroyed by DHT, minoxidil will no longer be able to have any more regrowth effects on that follicle. Other treatment options include tretinoin combined with minoxidil, ketoconazole shampoo, spironolactone, alfatradiol, and topilutamide (fluridil).

Procedures

More advanced cases may be resistant or unresponsive to medical therapy, and require hair transplantation. Naturally occurring units of one to four hairs, called follicular units, are excised and moved to areas of hair restoration. These follicular units are surgically implanted in the scalp in close proximity and in large numbers. The grafts are obtained from either follicular unit transplantation (FUT) or follicular unit extraction (FUE). In the former, a strip of skin with follicular units is extracted and dissected into individual follicular unit grafts. The surgeon then implants the grafts into small incisions, called recipient sites. Specialized scalp tattoos can also mimic the appearance of a short, buzzed haircut.

Alternative therapies

Many people use unproven treatments. There is no evidence for vitamins, minerals, or other dietary supplements. As of 2008, there is little evidence to support the use of lasers to treat male-pattern hair loss. The same applies to special lights. Dietary supplements are not typically recommended.

Prognosis

Psychological

Androgenic alopecia is typically experienced as a "moderately stressful condition that diminishes body image satisfaction". However, although most men regard baldness as an unwanted and distressing experience, they usually are able to cope and retain integrity of personality.

Although baldness is not as common in women as in men, the psychological effects of hair loss tend to be much greater. Typically, the frontal hairline is preserved, but the density of hair is decreased on all areas of the scalp. Previously, it was believed to be caused by testosterone just as in male baldness, but most women who lose hair have normal testosterone levels.

Epidemiology

Female androgenic alopecia has become a growing problem that, according to the American Academy of Dermatology, affects around 30 million women in the United States. Although hair loss in females normally occurs after the age of 50 or even later when it does not follow events like pregnancy, chronic illness, crash diets, and stress among others, it is now occurring at earlier ages with reported cases in women as young as 15 or 16.

Society and culture

Certain studies have suggested androgenic alopecia conveys survival advantage.

Studies have been inconsistent and not stable across cultures how balding men rate on the attraction scale. While a study from South Korea showed most people rated balding men as less attractive, a more recent survey of 1000 Welsh women rated bald and gray haired men quite desirable.

Proposed social theories for male-pattern hair loss include that baldness signaled dominance, social status, or longevity. Biologists have hypothesized the larger sunlight exposed area would allow more vitamin D to be synthesized, which might have been a "finely tuned mechanism to prevent prostate cancer", as the malignancy itself is also associated with higher levels of DHT.

Myths

An ancient phenomenon:
Greek philosophers with and without much hair (from left to right: Socrates, Antisthenes, Chrysippus, and Epicurus, fifth to third centuries BC)

Many myths are given regarding the possible causes of baldness and its relationship with one's virility, intelligence, ethnicity, job, social class, wealth, etc. While skepticism may be warranted in many cases due to a lack of scientific validation, some claims may have a degree of underlying truth and are supported by research.

You inherit baldness from your mother's father.

A 50% chance exists for a person to share the same X chromosome as his maternal grandfather. Because women have two X chromosomes, they have two copies of the androgen receptor gene, while men only have one. However, a person with a balding father also has a significantly greater chance of experiencing hair loss.

Weight training and other types of physical activity cause baldness.

Because it increases testosterone levels, many internet forums have put forward the idea that weight training and other forms of exercise increase hair loss in predisposed individuals. Although scientific studies do support a correlation between exercise and testosterone, no direct study has found a link between exercise and baldness. However, a few have found a relationship between a sedentary lifestyle and baldness, suggesting some exercise is beneficial. The type or quantity of exercise may influence hair loss. Testosterone levels are not a good marker of baldness, and many studies actually show paradoxical low testosterone in balding persons, although research on the implications is limited.

Intellectual activity or psychological problems can cause baldness.

This notion may have arisen because cholesterol is involved in the process of neurogenesis and is the base material from which the body ultimately manufactures DHT. While the notion that bald men are more intelligent may lack credibility in the modern world, in the ancient world, if a person were bald, he likely had an adequate amount of fat in his diet. Thus, his mental development was probably not stunted by malnutrition during his crucial formative years, and he was more likely to be wealthy and to have had access to a formal education. However, a sedentary lifestyle is less likely to correlate with intelligence in the modern world, and dietary fat content is not linked to economic class in modern developed countries. Another possibility is that for some people, social standing accrued through intelligence can compensate in mating for physical attractiveness lowered by hair loss and therefore produce male offspring who are prone to both high intellect and hair loss. However, by way of better socioeconomic standing and in turn more access to hair loss treatments, an association between intelligence and actual hair loss is less likely in recent times. Total testosterone exhibits a positive relation to tactual-spatial abilities and to the degree of lateralization. Total testosterone is negatively correlated with verbal fluency. Testosterone in the saliva is also significantly positively correlated to tactual-spatial test scores and, in addition, to field independence. DHT and the ratio DHT/total testosterone are positively related to verbal fluency and negatively to the degree of lateralization of tactual-spatial performance.

Baldness can be caused by emotional stress, sleep deprivation, etc.

Emotional stress has been shown to accelerate baldness in genetically susceptible individuals. Stress due to sleep deprivation in military recruits lowered testosterone levels, but is not noted to have affected SHBG. Thus, stress due to sleep deprivation in fit males is unlikely to elevate DHT, which causes male pattern baldness. Whether it can cause hair loss by some other mechanism is not clear.

Bald men are more 'virile' or sexually active than others.

Levels of free testosterone are strongly linked to libido and DHT levels, but unless free testosterone is virtually nonexistent, levels have not been shown to affect virility. Men with androgenic alopecia are more likely to have a higher baseline of free androgens. However, sexual activity is multifactoral, and androgenic profile is not the only determining factor in baldness. Additionally, because hair loss is progressive and free testosterone declines with age, a male's hairline may be more indicative of his past than his present disposition.

Frequent ejaculation causes baldness.

Many misconceptions exist about what can help prevent hair loss, one of these being that lack of sexual activity will automatically prevent hair loss. While a proven direct correlation exists between increased frequency of ejaculation and increased levels of DHT, as shown in a recent study by Harvard Medical School, the study suggests that ejaculation frequency may be a sign, rather than necessarily a cause, of higher DHT levels. Another study shows that although sexual arousal and masturbation-induced orgasm increase testosterone concentration around orgasm, they reduce testosterone concentration on average (especially before abstinence) and because about 5% of testosterone is converted to DHT, ejaculation does not elevate DHT levels.

The only published study to test correlation between ejaculation frequency and baldness was probably large enough to detect an association (1390 subjects) and found no correlation, although persons with only vertex androgenetic alopecia had had fewer female sexual partners than those of other androgenetic alopecia categories (such as frontal or both frontal and vertex). One study may not be enough especially in baldness, where there is a complex with age. Marital status has been shown in some studies to influence hair loss in cross-sectional studies (NHANES1).

Names

Male pattern hair loss is also known as androgenic alopecia, androgenetic alopecia (AGA), alopecia androgenetica and male pattern baldness (MPB).

Other animals

Animal models of androgenic alopecia occur naturally and have been developed in transgenic mice; chimpanzees (Pan troglodytes); bald uakaris (Cacajao rubicundus); and stump-tailed macaques (Macaca speciosa and M. arctoides). Of these, macaques have demonstrated the greatest incidence and most prominent degrees of hair loss.

Baldness is not a trait unique to human beings. One possible case study is the maneless male Tsavo lion. The Tsavo lions' prides are unique in that they frequently have only a single male lion with usually seven or eight adult females, as opposed to four females in other lion prides. Tsavo males may have heightened levels of testosterone, which could explain their reputation for aggression and dominance, indicating that lack of mane may at one time have had an alpha correlation.

External links

• NLM- Genetics Home Reference