US Pharm. 2008;33(8):49.

Androgenic alopecia, or male pattern baldness, is the most common form of alopecia, occurring in more than 50% of men. The prevalence increases with age, and approximately 80% of Caucasian males experience the condition by age 70. The incidence varies by race, and Caucasian males are affected more often than males of other races. 1 Hair loss is gradual for most men, occurring over a 15- to 25-year period; however, some men experience complete hair loss within a period of five years or less.2 Hair loss usually occurs in patterns as defined by the Hamilton-Norwood scale of male pattern baldness, starting with recession of the frontal hairline and proceeding with progressive thinning and loss of the hair on the vertex of the scalp. These two regions of hair loss eventually meet, leading to baldness of the top of the scalp. This is the typical progression of hair loss; however, variations may occur.3 The pattern typically resembles an "M" in shape.4

Pathophysiology of Alopecia
Androgenic alopecia is a hereditary condition. There is debate over the specific gene that causes it; however, some believe that androgenic alopecia is passed down from father to son.3 The condition is directly linked to androgens, particularly dihydrotestosterone (DHT). DHT is the most abundant androgen in the skin and is converted from testosterone by alpha reductase.5 The impact of androgen on hair is site specific. For example, hair located on the chest, pubic area, and beard area reacts positively to the presence of androgens by producing terminal--or thick, pigmented--hair. In contrast, hair follicles located on the head are reduced in size and produce nonpigmented vellus hairs in response to androgens. Over time, the hair growth cycle is affected by androgens.

The hair growth cycle involves three phases: the anagen, catagen, and telogen phases. The anagen, or hair growth phase, is the first phase of hair growth, lasting between two to six years. This phase is followed by the catagen phase, a transition phase lasting approximately one to two weeks, and subsequently by the telogen, or resting, phase lasting five to six weeks. After the telogen phase, the anagen phase starts again.3 Men with alopecia have a shorter anagen phase and a longer telogen phase, which eventually results in very short hair that fails to emerge from the follicle, thereby causing baldness.2,3

Psychological Impact of Androgenic Alopecia

Alopecia not only affects men physically, but can also have a psychological impact on those afflicted by the condition. Men often associate hair with attractiveness and virility. Once hair loss occurs, men can lose confidence and satisfaction with their physical appearance. Studies have shown that factors such as young age, no involvement in a romantic relationship, and preexisting, poor self-esteem contribute to a greater risk of a psychological impact from hair loss.1 It has also been noted that males experiencing hair loss have a greater incidence of depression and anxiety than those who do not experience this condition. There are limitations to this finding, as stressful life events could also lead to psychological manifestations or even alopecia.6 The psychological effects of the condition need to be taken into account by practitioners as they counsel men with androgenic alopecia and educate them on available treatment options.

There are currently two FDA-approved pharmacologic treatments for androgenic alopecia: minoxidil and finasteride.

Minoxidil

Minoxidil topical solution was the first of the FDA-approved treatments for androgenic alopecia to be placed on the market. This product was first used in the oral form for the treatment of hypertension and was found to have a side effect of hypertrichosis.7 The exact mechanism of action in hair growth is unclear; however, the proposed mechanisms of action are normalization of hair follicle structure, conversion of vellus hairs to terminal hairs, and amplification of the number of hair follicles in the anagen phase of hair growth.8 It is clear that the mechanism is not due to vasodilation, as hair continues to grow in the absence of blood flow.9

Minoxidil is available in a 2% and 5% topical solution and a 5% foam, all of which are available to consumers OTC. Numerous studies have been conducted indicating that minoxidil causes regrowth of hair. Two double-blind, placebo-controlled trials studied hair weight measurements and found that both strengths of minoxidil were more effective than placebo in growing hair. Over a period of two years, hair loss subsided in patients treated with both strengths of minoxidil while hair loss continued in those treated with placebo. Subsequently, discontinuation of the product resulted in hair loss in the treatment group that matched hair loss in the placebo group within a period of six months.7 Additional studies have proven that the 5% solution is superior in efficacy to the 2% solution in males with androgenic alopecia.9

A one-year safety trial was conducted in over 20,000 patients using topical minoxidil and assessed patients for an increased risk of hospitalization or death. At the end of the trial it was found that topical minoxidil did not cause an increased risk of hospitalization or death in these patients. The study looked specifically at cardiovascular events and found no significant difference in patients using minoxidil compared to those in the control group. In addition, more than 90% of patients in the trial at six, nine, and 12 months felt that the product was working to reduce hair loss.10

Minoxidil is helpful in males experiencing frontal or vertex alopecia or thinning of hair. The growth is not due to the formation of new hair, but to the transformation of existing hair from miniaturized hair follicles to terminal hair. After that point, there is stabilization of the hair that has grown.7

Although minoxidil promotes hair growth in men, the therapy does have the potential to create compliance issues. A patient must continue use of the product indefinitely or hair loss will occur. Men using minoxidil should be encouraged to use the 5% solution if tolerated. Patients should be counseled to apply the solution directly to the scalp to maximize effectiveness and minimize cosmetic issues such as hair oiliness. If applied directly to the hair, the product leaves a sticky residue. Patients should also be told that response to treatment is variable.8 Those experiencing pruritus of the scalp should be given a topical corticosteroid to use along with minoxidil.9 Patients should not expect results until four to six months into therapy and should not look for maximum results until at least one year of use. Dosing, adverse events, and pricing of minoxidil are included in TABLE 1.



Overall, minoxidil appears to be a safe and effective therapy in select patients with androgenic alopecia; however, patients should realize that efficacy depends on continued use of the product.

Finasteride
A second product, indicated for the treatment of androgenic alopecia, is oral finasteride. Finasteride is an inhibitor of the type II 5-alpha reductase isoenzyme, which is predominant in the scalp hair root sheath.8 By blocking 5-alpha reductase, finasteride inhibits the conversion of testosterone to DHT.7 As discussed earlier, DHT can lead to hair loss in the scalp. Finasteride 1 mg has been found to reduce DHT levels in the scalp by over 60%.5

Clinical trials have proven the efficacy of finasteride. Several of the trials, treating men with vertex and midscalp hair loss, found a significant increase in hair count in patients treated with finasteride 1 mg versus placebo. Hair growth occurred over the first year, and the drug must be continued indefinitely to maintain new hair.1,7 Evidence of hair growth can become apparent within the first four months of treatment; however, patients should continue treatment for at least 24 months before deciding upon its effectiveness.2 Studies have concluded that finasteride stabilizes hair loss in 80% of patients with vertex hair loss and in 70% of patients with frontal hair loss. In addition, hair regrowth occurs in 37% of men with frontal hair loss and in 61% of men with vertex hair loss.7 Dosing, adverse effects, and pricing are included in TABLE 1.

The FDA has approved the use of finasteride for patients ages 18 to 41 with mild to moderate male pattern baldness in the midfrontal area. Patients should be made aware that no change in hair density indicates that the product is effective because it has maintained existing hair. In patients with androgenic alopecia, hair loss will continue over time. Caution should be taken by women of childbearing age when handling the product due to the potential to cause abnormalities of the external genitalia in a developing male fetus.11 There are no studies evaluating the semen of men taking finasteride and the potential for problems to a fetus; however, the product is labeled as Pregnancy Category X.9

A randomized, open, comparative trial in 65 patients with androgenic alopecia compared minoxidil 5% to finasteride 1 mg. The study was carried out over a period of 52 weeks in males ranging from 18 to 50 years. At the end of the study, 80% of patients in the finasteride group experienced some form of hair growth in comparison to 52% of patients in the minoxidil group (P <0.05). Both products were well tolerated and showed efficacy in some patients.11 One open, randomized, parallel-group study was conducted in 100 males with androgenic alopecia and compared finasteride 1 mg, topical 2% minoxidil, and 2% ketoconazole shampoo alone and all three in combination. It was found that finasteride alone or in combination with the other agents provided a statistically significant improvement in hair growth over minoxidil alone.12

Other Therapies
Several other drugs have been evaluated for their potential role in patients with androgenic alopecia; however, the sample sizes are very small and outcomes are varied. Small studies have been conducted using a combination of topical tretinoin with topical minoxidil, and these resulted in some hair growth. A drawback to this combination is that the two products cannot be compounded into one solution due to incompatibility; therefore, they must be applied at different times of the day. In addition, some patients cannot tolerate the irritation experienced with topical tretinoin, which has not been widely studied to decide whether or not this is an appropriate therapy. Spironolactone 200 mg daily has been studied in a few small trials due to its mild antiandrogenic effect and has shown some clinical benefit; however, it is not widely used.7

In addition to pharmacologic treatment, there are several nonpharmacologic options for men experiencing androgenic alopecia. These include hair transplantation, scalp reduction surgery, and cosmetic aids such as wigs and hairpieces.1

To date, there are no other approved products for androgenic alopecia; however, minoxidil and finasteride are safe, effective treatments for the condition. The results with these products are not miraculous; still, they have been shown to reduce the progression of hair loss and promote hair growth in men. Men need to be counseled on realistic expectations of the products and must realize that results vary from patient to patient. They must also be committed to a lifetime of treatment, as discontinuation of both products results in a continued progression of hair loss.

REFERENCES

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2. Sinclair R. Fortnightly review: male pattern androgenetic alopecia. BMJ. 1998;317:865-869.

3. Ellis JA, Sinclair R, Harrap SB. Androgenic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med.2002:1-11.

4. Springer K, Brown M, Stulberg DL. Common hair loss disorders. Am Fam Physician. 2003;68:93-102.

5. Otberg N, Finner A, Shapiro J. Androgenic alopecia. Endocrinol Metab Clin North Am. 2007;36:379-398.

6. Hunt N, McHale S. The psychological impact of alopecia. BMJ. 2005;331:951-953.

7. Bolduc C, Shapiro J. Management of androgenic alopecia. Am J Clin
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8. Sinclair, RD. Management of male pattern hair loss. Cutis. 2001;68:35-40.

9. Haber RS. Pharmacologic management of pattern hair loss. Facial Plast Surg Clin North Am. 2004:181-189.

10. Shapiro J. Safety of topical minoxidil solution: a one-year, prospective, observational study. J Cutan Med Surg. 2003;7:322-329.

11. Arca E, Acikgoz G, Tastan HB, et al. An open, randomized, comparative study of oral Finasteride and 5% Topical Minoxidil in male androgenic alopecia. Dermatology. 2004;209:117-125.

12. Khandpur S, Suman M, Reddy BS. Comparative efficacy of various treatment regimens for androgenetic alopecia in men. J Dermatol. 2002;29:489-498.

13. www.drugstore.com. Accessed March 26, 2008.

14. www.rogaine.com/Mens/DrugFacts. Accessed June 12, 2008.

15. www.propecia.com/finasteride/propecia/consumer/product-information/pi. Accessed June 12, 2008.

16. Micromedex. Vol. 122. Montvale, NJ: Thomson Healthcare; 1974-2008.

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