Pattern hair loss (also known as androgenetic alopecia (AGA)[1]) is a hair loss condition that primarily affects the top and front of the scalp.[2][3] In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front hairline, loss of hair on the crown (vertex) of the scalp, or a combination of both. Female-pattern hair loss (FPHL) typically presents as a diffuse thinning of the hair across the entire scalp.[3]

Male pattern hair loss seems to be due to a combination of oxidative stress,[4] the microbiome of the scalp,[5][6] genetics, and circulating androgens; particularly dihydrotestosterone (DHT).[3] Men with early onset androgenic alopecia (before the age of 35) have been deemed as the male phenotypic equivalent for polycystic ovary syndrome (PCOS).[7][8][9][10] As an early clinical expression of insulin resistance and metabolic syndrome, AGA is related to being an increased risk factor for cardiovascular diseases, glucose metabolism disorders,[11] type 2 diabetes,[12][13] and enlargement of the prostate.[14]

The cause in female pattern hair loss remains unclear,[3] androgenetic alopecia for women is associated with an increased risk of polycystic ovary syndrome (PCOS).[15][16][17]

Management may include simply accepting the condition[3] or shaving one's head to improve the aesthetic aspect of the condition.[18] Otherwise, common medical treatments include minoxidil, finasteride, dutasteride, or hair transplant surgery.[3] Use of finasteride and dutasteride in women is not well-studied and may result in birth defects if taken during pregnancy.[3]

Pattern hair loss by the age of 50 affects about half of males and a quarter of females.[3] It is the most common cause of hair loss. Both males aged 40–91 [19] and younger male patients of early onset AGA (before the age of 35), had a higher likelihood of metabolic syndrome (MetS) [20][21][22][23] and insulin resistance.[24] With younger males, studies found metabolic syndrome to be at approximately a 4x increased frequency which is clinically deemed as significant.[25][26] Abdominal obesity, hypertension and lowered high density lipoprotein were also significantly higher for younger groups.[27]

Signs and symptoms
Pattern hair loss is classified as a form of non-scarring hair loss.

Male-pattern hair loss begins above the temples and at the vertex (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.[28]

Female-pattern hair loss more often causes diffuse thinning without hairline recession; similar to its male counterpart, female androgenic alopecia rarely leads to total hair loss.[29] The Ludwig scale grades severity of female-pattern hair loss. These include Grades 1, 2, 3 of balding in women based on their scalp showing in the front due to thinning of hair.[citation needed]

In most cases, receding hairline is the first starting point; the hairline starts moving backwards from the front of the head and the sides.[30][citation needed]

Causes
Hormones and genes
KRT37 is the only keratin that is regulated by androgens.[31] This sensitivity to androgens was acquired by ♥♥♥♥ sapiens and is not shared with their great ape cousins. Although Winter et al. found that KRT37 is expressed in all the hair follices of chimpanzees, it was not detected in the head hair of modern humans. As androgens are known to grow hair on the body, but decrease it on the scalp, this lack of scalp KRT37 may help explain the paradoxical nature of Androgenic alopecia as well as the fact that head hair anagen cycles are extremely long.[citation needed]
Androgens can interact with the Wnt signalling pathway to cause hair loss

The initial programming of pilosebaceous units of hair follicles begins in utero.[32] The physiology is primarily androgenic, with dihydrotestosterone (DHT) being the major contributor at the dermal papillae. Men with premature androgenic alopecia tend to have lower than normal values of ♥♥♥ hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), testosterone, and epitestosterone when compared to men without pattern hair loss.[10] Although hair follicles were previously thought to be 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.[33][34][non-primary source needed]

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 ♥♥♥♥♥♥ 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 can suppress it at the temples and scalp vertex, a condition that has been referred to as the 'androgen paradox'.[35]

Men with androgenic alopecia typically have higher 5α-reductase, higher total testosterone, higher unbound/free testosterone, and higher free androgens, including DHT.[36] 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.[37] The genetic corollary that codes for this enzyme has been discovered.[38] Prolactin has also been suggested to have different effects on the hair follicle across gender.[39]

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.[35] Other research suggests the enzyme prostaglandin D2 synthase and its product prostaglandin D2 (PGD2) in hair follicles as contributive.[40]

These observations have led to study at the level of the mesenchymal dermal papillae.[41] Types 1 and 2 5α reductase enzymes are present at pilosebaceous units in papillae of individual hair follicles.[42] They catalyze formation of the androgens testosterone and DHT, which in turn regulate hair growth.[35] Androgens have different effects at different follicles: they stimulate IGF-1 at facial hair, leading to growth, but can also stimulate TGF β1, TGF β2, dickkopf1, and IL-6 at the scalp, leading to catagenic miniaturization.[35] Hair follicles in anaphase express four different caspases. Significant levels of inflammatory infiltrate have been found in transitional hair follicles.[43] Interleukin 1 is suspected to be a cytokine mediator that promotes hair loss.[44]

The fact that hair loss is cumulative with age while androgen levels fall as well as the fact that finasteride does not reverse advanced stages of androgenetic alopecia remains a mystery, but possible explanations are higher conversion of testosterone to DHT locally with age as higher levels of 5-alpha reductase are noted in balding scalp, and higher levels of DNA damage in the dermal papilla as well as senescence of the dermal papilla due to androgen receptor activation and environmental stress.[45] The mechanism by which the androgen receptor triggers dermal papilla permanent senescence is not known, but may involve IL6, TGFB-1 and oxidative stress. Senescence of the dermal papilla is measured by lack of mobility, different size and shape, lower replication and altered output of molecules and different expression of markers. The dermal papilla is the primary location of androgen action and its migration towards the hair bulge and subsequent signaling and size increase are required to maintain the hair follicle so senescence via the androgen receptor explains much of the physiology.[citation needed]

Inheritance
Male pattern baldness is a complex genetic condition with a "particularly stro