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Male Pattern Hair Loss: Androgenetic Alopecia

Androgenic Alopecia: Etiology, Frequency, Causes, Pathophysiology and Treatments of Hair Loss

Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic “M” shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.

The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.

Androgenic alopecia in men has been associated with several other medical conditions including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia.

In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body (hirsutism), and weight gain.

Etiology of Androgenetic Alopecia

Androgenetic alopecia, as the name suggests has a clear genetic predisposition and is likely due to an excessive response to androgen.

Pattern alopecia is a polygenic disorder with variable penetrance, and both maternal and paternal genes are involved. There is a familial predisposition to androgenic alopecia with sons at a five to six-time higher relative risk if their fathers were balding.

Androgenic alopecia also requires androgen to occur. It develops only after puberty. Males castrated before puberty and those with androgen insensitivity syndrome do not have pattern baldness. Both hormone metabolism and androgen receptors play a key role in androgenic alopecia.

Frequency of Androgenetic Alopecia

Androgenetic alopecia is a frequent cause of hair loss in both men and women. This form of hair loss affects an estimated 50 million men and 30 million women in the United States.

Androgenetic alopecia can start as early as a person’s teens and the risk increases with age; more than 50 percent of men over age 50 have some degree of hair loss. In women, hair loss is most likely after menopause.

Causes of Androgenetic Alopecia

A variety of genetic and environmental factors likely play a role in causing hair loss. Although researchers are studying risk factors that may contribute to this condition, most of these factors remain unknown.

Researchers have determined that this form of hair loss is related to hormones called androgens, particularly an androgen called dihydrotestosterone.

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.

Hair growth begins under the skin in structures called follicles. Each strand of hair normally grows for 2 to 6 years, goes into a resting phase for several months, and then falls out.

The cycle starts over when the follicle begins growing new hair. Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair. Additionally, there is a delay in the growth of new hair to replace strands that are shed.

Although researchers suspect that several genes play a role in androgenetic alopecia, variations in only one gene, Androgen Receptor (AR), have been confirmed in scientific studies. The AR gene provides instructions for making a protein called an androgen receptor.

Androgen receptors allow the body to respond appropriately to dihydrotestosterone and other androgens. Studies suggest that variations in the Androgen Receptor (AR) gene lead to increased activity of androgen receptors in hair follicles.

It remains unclear, however, how these genetic changes increase the risk of hair loss in men and women with androgenetic alopecia.

Researchers continue to investigate the connection between androgenetic alopecia and other medical conditions, such as coronary heart disease and prostate cancer in men and polycystic ovary syndrome in women.

They believe that some of these disorders may be associated with elevated androgen levels, which may help explain why they tend to occur with androgen-related hair loss. Other hormonal, environmental, and genetic factors that have not been identified also may be involved.

Pathophysiology of Androgenetic Alopecia

Activation of the androgen receptor shortens the anagen or growth phase in the normal hair growth cycle.

In androgenetic alopecia, excessive activation leads to follicular miniaturization through a progressively shorter anagen phase, resulting in thinner and shorter hair follicles which in the end may not even penetrate through the epidermis. Pathological specimens will show a decreased 5:0 ratio of anagen to telogen hair where the norm is 12:1.

Androgenic alopecia patients have higher production of dihydrotestosterone, and higher levels of 5 alpha-reductase and androgen receptors in balding scalp.

There are two major isoforms of the 5 alpha-reductase enzymes. The 5 alpha-reductase converts testosterone to DHT (dihydrotestosterone), which has a much greater affinity for the androgen receptor. Type 2 5 alpha-reductase enzyme plays a greater role in androgenetic alopecia.

a. Type 1:

5 alpha-reductase enzymes are in sebaceous glands, keratinocytes, and sweat glands.

b. Type 2:

5 alpha-reductase enzymes are in the outer root sheath of hair follicles, epididymis, vas deferens, seminal vesicles, and prostate.

The normal hair growth cycle consists of four phases: anagen (growth), catagen (involution), telogen (resting), and exogen (shedding of hair). Eighty percent to 90% of hair is in the anagen phase which lasts 2 to 6 years and determines the hair length; less than 5% are in catagen, and the rest are in telogen. Shedding of 100 hairs a day (exogen) is normal.

Hair Loss Treatments

There are two FDA-approved drugs for pattern baldness: topical minoxidil and finasteride, both of which require at least a 4- to 6-month trial before noticing improvement and must be used indefinitely to maintain a response.

As such, medication adherence often can be poor. Furthermore, initiation of the drug may cause an initial shedding phase. They work better together.

a. Topical Minoxidil

Topical minoxidil is available over-the-counter and in various strengths, up to 5% solution. Higher strengths are more effective. The most common adverse effects are pruritus and local irritation with resulting flaking. The latter is usually due to propylene glycol or alcohol in the formulation of the drug.

Minoxidil is a potassium channel blocker and widens blood vessels which hypothetically allow more oxygen, blood, and nutrients to follicles and promote the anagen phase.

b. Finasteride

Finasteride is a 5 alpha-reductase type 2 inhibitor and not an anti-androgen. It is prescribed at 1 mg daily and is more effective at increasing hair regrowth at the vertex than the frontal area of the scalp.

The efficacy of finasteride is unclear in female pattern baldness and contraindicated for women with reproductive potential (Category X) as it can cause a male fetus to develop ambiguous genitalia.

Adverse effects include sexual dysfunction, which usually reduces with time; increased risk of high-grade prostate cancer because PSA is masked and detected later; and case reports of persistent diminished libido and erectile dysfunction.

c. Other Drugs

Other drugs used in pattern baldness are not FDA-approved. Dutasteride is three times more potent on type II 5 alpha-reductase enzyme, 100 times more potent on type 1 enzyme, and often used on patients who failed finasteride. The adverse effect profile is similar to finasteride.

In women, oral antiandrogens such as spironolactone are often used. Spironolactone is a very weak partial agonist to the androgen receptor, blocking the much more potent DHT and free testosterone from interacting with the androgen receptor, thus physiologically behaving like a direct antagonist.

It also inhibits androgen synthesis and enhances the conversion of testosterone to estradiol. Cyproterone acetate may be used internationally but is not available in the United States. Anti-androgens are more effective if there are other signs of virilization.

Hair transplant is effective and cosmetically satisfactory to the patient. However, patients need to have a sufficient number of donor plugs (greater than 40 follicular units/cm2) to cover the bald area. New techniques have made hair transplants more cosmetically pleasing and natural looking.

Red light or laser at 660 nm also has demonstrated efficacy for hair loss and is available OTC for pattern baldness.

Other proposed treatments include saw palmetto extract (Serenoa Repens); prostaglandin analogs like latanoprost and bimatoprost, which may be cost prohibitive; and multiple growth factors, which are a theoretical reason why platelet-rich plasma and adipose-derived stem cells may be used as adjunctive to treatments listed.

Other Names of Androgenetic Alopecia

  • Androgenic Alopecia
  • Male Pattern Alopecia
  • Male Pattern Baldness
  • Pattern Baldness

Primary References:

  1. Confirmation of the association between male pattern baldness and the androgen receptor gene. Levy-Nissenbaum E, Bar-Natan M, Frydman M, Pras E. Eur J Dermatol. 2005 Sep-Oct;15(5):339-40. 
  2. Update on the pathogenesis, genetics, and medical treatment of patterned hair loss. Schweiger ES, Boychenko O, Bernstein RM. J Drugs Dermatol. 2010 Nov;9(11):1412-9. Review.
  3. Update on the genetics of androgenetic alopecia, female pattern hair loss, and alopecia areata: implications for molecular diagnostic testing. Yazdan P. Semin Cutan Med Surg. 2012 Dec;31(4):258-66. DOI: 10.1016/j.sder.2012.08.003. Review. Retraction in: Semin Cutan Med Surg. 2015 Mar;34(1):48.

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