Promising Therapies for Treating and/or Preventing Androgenic Alopecia

Kevin J. McElwee, PhD; Jerry Shapiro, MD, FRCPC

Disclosures

Skin Therapy Letter. 2012;17(6) 

In This Article

Androgenetic Alopecia

Clinical Presentation

In most men, AGA develops with a distinctive "patterned" hair line recession. In women, the presentation may be less clear; typically women will develop a diffuse thinning over the top of the scalp yielding a "Christmas tree" pattern with more thinning towards the front, though the frontal hairline is maintained.[2] Occasionally men may develop a female presentation of hair loss and women, primarily those experiencing excess androgen activity, may develop a more male-like hair loss pattern. Also of note, frontal fibrosing alopecia in women, a scarring alopecia with hairline recession, has been frequently misdiagnosed as AGA.[3] Diffuse AGA may be difficult to distinguish from telogen effluvium. Indeed, telogen effluvium may spur AGA onset and the increased shedding of telogen effluvium can be an early phase characteristic of AGA. Where diagnosis is in doubt, a biopsy may clarify.[4]

Biochemistry

Research on subjects with androgen insensitivity syndromes, or 5α reductase deficiency, implies that AGA is induced via activation of androgen receptors in hair follicles by dihydrotestosterone (DHT). DHT binds to androgen receptors with five times the tenacity of testosterone and consequently has greater downstream activation potency.[5] Two distinct forms of 5α reductase (types 1 and 2) differ in their tissue distribution; type 2 is most active in hair follicles, but both likely contribute to AGA. The primary precursor of DHT in men is testosterone, but dehydroepiandrosterone (DHEA) and other weaker androgens, are the precursors for DHT in women. The intracellular signaling cascade after androgen receptor binding is poorly understood, but receptor binding leads to increased production of cytokines, such as TGFbeta1 and 2, which promote telogen and dermal papilla cell senescence.[6,7] The density of androgen receptors in hair follicles varies with location. Occipital hair follicles, with a low number of androgen receptors, have little or no response to DHT. Consequently, hair loss is mostly restricted to the scalp vertex and fronto-temporal areas.

Genetics and Diagnostic Tests

AGA susceptibility is largely determined by genetics, though the environment may also play a minor role. Androgen receptor polymorphisms probably make the key determination for androgen responsiveness, but 5α reductase, aromatase, and sex hormone binding globulin (SHBG) genes may also contribute along with other hormone metabolism associated genes.[8] While the complete genetic picture is not clear, at least one company claims to have a gene polymorphism based diagnostic test (HairDX™) that will predict the chances of future AGA development.[9,10] For young patients concerned about hair loss this test may help to define the value of early treatment initiation. Perhaps of more immediate practical significance, a test that predicts responsiveness to treatment with finasteride is also available.[11] In women, serum ferritin levels may also be assessed to determine iron deficiency, thyrotropin levels may be evaluated to rule out thyroid dysfunction, and free testosterone is assessed when androgen excess is suspected. If serum ferritin is low, iron supplementation has been recommended as an enabler of response to other treatments.[2]

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