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Clinical Updates

Marcio Rutowitsch, MD, PhD

Androgenetic Alopecia

Marcio Rutowitsch

Wednesday, December 15, 2004

Androgenetic alopecia (AGA) occurs in both sexes when there is progressive miniaturization of hair follicles, shortening of the anagen phase of the hair cycle, and prolongation of the telogen phase. The scalp has a three-phase cycle of hair, with almost 90% of hair in the anagen or growth phase (which may last up to 2-6 years), 1% in the catagen phase (which may last 3 weeks), and 10% in the telogen or resting phase (which may last 3 months). This ratio is usually uniformly distributed over the entire scalp. When the hair in the telogen phase is expelled, another follicle pile in the anagen VI phase emerges to replace it, although this does not always occur. In fact, some follicles may remain empty after the final moment of the telogen phase, and this new phase is known as the kenogen or lag phase.1

Some men tolerate androgenetic alopecia (AGA) without concern, while other men and many women find it to be unacceptable when hair loss goes beyond culturally defined limits. Substantial hair loss may cause anguish and low self-esteem, confirming the concept that hair has significant psychological function. Thus, hair loss should be approached as both a medical and an aesthetic problem.2

AGA is a common genetic condition in which hair loss occurs due to the action of circulating androgens in genetically susceptible men and women. Thinning of the hair begins between 12 and 40 years of age in both sexes,3,4 and approximately 50% of the population expresses this trait to some degree before 50 years of age.5,6 Research has been directed toward understanding the miniaturization of the hairs. It is unknown whether this is an abrupt phenomenon or whether it occurs over several hair cycles. It's also unknown how this phenomenon is produced.1,7,8

In order to understand the pathogenesis of AGA, it is important to know the different embryological origins of dermal papilla cells of the follicle piles in different areas of the scalp. The frontal-parietal dermis is derived from the neural crest, while that of the occipital-temporal is derived from the mesoderm. For this reason, the different follicles may have different responses to the same androgenic stimulus.9

Follicles in areas affected by AGA undergo a process of miniaturization, while those in other areas remain unaffected (such as those in the occipital region). In most cases of female AGA, as in almost all cases of male AGA, there are no alterations in the production of hormones. The problem lies in the target organ - that is, how each hair follicle responds to circulating androgens. When androgens reach the dermal papilla cells, they may be metabolized by 5-alpha-reductase to dihydrotestosterone (DHT). DHT, which is more potent than testosterone, causes miniaturization of follicles in the area of the AGA. Androgens can also be metabolized by aromatase-producing 17-beta-estradiol, an estrogen that does not cause involution of the follicle. DHT links to a cytoplasmic receptor and penetrates the cell nucleus, initiating its action at the level of the DNA with transcription of messengers; it starts miniaturization by DHT-induced acceleration of the mitotic rate of the matrix, which shortens the time allowed for differentiation. Miniaturization is also started by the increased telogen shedding that occurs as a result of the shortening of the hair cycle, which increases telogen number per unit of time. The duration of miniaturization and the frequency with which miniaturization occurs vary in accordance with age and the severity of the AGA; how this mechanism is related to DHT remains uncertain.1,6,8

In most women, AGA appears at an early age. Thinning occurs with reductions in both the physiological diameter and the number of hairs. There is thinning of the hairs on the apex of the scalp, with the retention of a strip of hair on the frontal region and the presence of miniaturized hairs, the Ludwig pattern. In men, there is a genetically determined deficiency, leading to loss and progressive thinning of hair, with an easily recognized clinical pattern marked by the anterior and medium bitemporal recession of the follicle piles in the scalp, the Hamilton pattern. This pattern may also be found in some women, where it is associated with androgenetic endocrine pathologies.10

Women with AGA usually have normal menses and pregnancies, so hormonal testing is not needed unless symptoms and signs of excess androgens are present (hirsutism, unresponsive cystic acne, virilization, or galactorrhoea).6 When any one of these features is present, laboratory measurement of total serum or free testosterone, dehydroepiandrosterone sulfate, and prolactin is indicated.

Scalp biopsies are taken from active sites of hair loss, and horizontal sectioning is preferred because of the large number of follicular structures that can be studied, where they show an increased number of miniaturized hairs.11,12

Figure 1. 21-year-old female patient with AGA Ludwig I, before topical 17 alpha-estradiol.

21 year-old female patient with AGA Ludwig I, before topical 17 alpha-estradiol

Figure 2. Same patient from Figure 1, 3 months later.

Same patient from Figure 1, 3 months later

Treatments may be either topical or systemic and are only suppressive, implying that there will be a reappearance of balding when treatment is stopped. On average, improvement takes 8-12 weeks to begin to appear. Of the topical medicines, the first to show results was a 2% concentration of minoxidil applied to the dry scalp twice a day. Mechanisms include increasing the rate of mitosis of the follicle cells and prolonging the duration of the anagen phase. Hair growth in areas other than that to which it has been applied is a well-known phenomenon, occurring more frequently in women than in men; it is reversible after stopping the drug. The Food and Drug Administration (FDA) has authorized a concentration of 5% for use in males. Some studies in women were conducted that showed strong trends favoring the 5% concentration, but they did not show enough statistical significance to gain final FDA approval.13,14,15

Another topical drug that has shown results is 17 alpha-estradiol applied to the scalp once a day.16 In an ex vivo study, it was suggested that its action occurs from an aromatase stimulus, with diversion of testosterone metabolism toward the production of 17 beta-estradiol, leading to the reduction of dihydrotestosterone synthesis.17

Figure 3. 32-year-old male patient with AGA Hamilton 4, before finasteride.

32 year-old male patient with AGA Hamilton 4, before finasteride


Figure 4. Same patient from Figure 3, 4 months after 1 mg of finasteride once a day.

Same patient from Figure 3, 4 months after 1 mg of finasteride once a day


One milligram (1 mg) of finasteride, a competitive inhibitor of 5-alpha-reductase type 2, taken orally, improves predominantly vertex male pattern hair loss, and it is generally well tolerated. It is contraindicated for women who are or may become pregnant, as it may cause abnormalities to the external genitalia of the male fetus. In post-menopause AGA, it is not effective.18,19

Surgical hair restoration, consisting of the implant of mini- and micro-grafts (transplanting of single hairs or groups of 3-6 hairs in the occipital area), provides satisfactory results, and is indicated in the most extensive cases of AGA. 20,21

Genetic therapy will probably be available in the next 10-20 years as an efficient treatment for AGA.


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  2. Rutowitsch MS, Antonio JR, Steiner D, Talarico S. Alopecia androgenetica. An Bras Dermatol. 1999;74:561-574.
  3. Hamilton JB. Patterned loss of hair in man: types and incidence. Ann N Y Acad Sci. 1951;53:708-728.
  4. Trancik RJ, Spindler JR, Cuddihy RV, et al. Clinician survey evaluating monoxidil topical solution in the treatment of androgenetic alopecia in patients under 18 years of age. Poster presented at 3rd Intercontinental Meeting of the Hair Research Societies, June 13-15, 2001, Tokyo, Japan; 129.
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  13. Olsen EA, Dunlap FE, Funicella T, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in males. J Am Acad Dermatol. 2002;47:377-385.
  14. Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized placebo controlled trial of 5% and 2% topical minoxidil solution in the treatment of androgenetic alopecia in females. J Am Acad Dermatol. 2004;50:541-553.
  15. Boeck C, Parker J, Shank J, Hordinsky M. Safety of long term therapy with 3% and 5% topical minoxidil in female androgenetic alopecia. In: van Nest D, Randall VA, eds. Hair Research for the Next Millennium. Amsterdam: Elsevier Science B; 1996:61-65.
  16. Orfanos CE, Vogels L. Topical therapy of androgenetic alopecia with 17-alfa-estradiol. Dermatologica. 1980;161:124-132.
  17. Hoffmann R, Niiyama S, Huth A, et al. 17 alfa-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo. Exp Dermatol. 2002;11:376-380.
  18. Price VH, Roberts JL, Hordinsky M, et al. Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. J Am Acad Dermatol. 2000;43:768-776.
  19. Whiting D, Olsen EA, Savin R, et al. Efficacy and tolerability of finasteride 1 mg in men aged 41 to 60 years with male pattern hair loss. Eur J Dermatol. 2003;13:150-160.
  20. Brandy DA. The art of mixing follicular groupings in hair restoration surgery. Dermatol Surg. 2004;30:846.
  21. Lam SM, Hempstead BR, Williams EF. A philosophy and strategy for surgical hair restoration: a 10-year experience. Dermatol Surg. 2002;28:1035-1042.