Mcpstough

Psychological Effect, Pathophysiology, and Management of
Androgenetic Alopecia in Men
DOW STOUGH, MD; KURT STENN, MD; ROBERT HABER, MD; WILLIAM M. PARSLEY, MD; JAMES E. VOGEL, MD; DAVID A. WHITING, MD; AND KEN WASHENIK, MD, PHD Androgenetic alopecia in men, or male pattern baldness, is recog- physically and psychologically harmful medical condition nized increasingly as a physically and psychologically harmful in some men1,2 that can be managed effectively by general- medical condition that can be managed effectively by generalistclinicians. This article discusses the clinical manifestations, epi- ist clinicians. Therefore, rather than being inconsequential demiology, physical and psychosocial importance, pathophysiol- among these men, androgenetic alopecia can be a harmful ogy, diagnosis, and management of androgenetic alopecia in men.
condition that warrants intervention.
Androgenetic alopecia affects at least half of white men by theage of 50 years. Although androgenetic alopecia does not appear Advances in surgical techniques make hair loss more to cause direct physical harm, hair loss can result in physical harm amenable to treatment than ever before; also, pharmaco- because hair protects against sunburn, cold, mechanical injury, therapy is now available that can retard, stop, or partially and ultraviolet light. Hair loss also can psychologically affect thebalding individual and can influence others’ perceptions of him. A reverse hair loss, can stimulate some hair regrowth,3 and is progressive condition, male pattern baldness is known to depend on safely prescribed on an outpatient basis. With the introduc- the presence of the androgen dihydrotestosterone and on a genetic tion of effective and tolerable pharmacotherapy, generalist predisposition for this condition, but its pathophysiology has notbeen elucidated fully. Pharmacotherapy, hair transplantation, and clinicians who are not experts in surgical techniques involv- cosmetic aids have been used to manage male pattern baldness.
ing hair transplantation can offer effective intervention.
Two US Food and Drug Administration–approved hair-loss pharma- The general public’s increasing knowledge of and readi- cotherapies—the potassium channel opener minoxidil and thedihydrotestosterone synthesis inhibitor finasteride—are safe and ness to explore pharmacological and surgical solutions to effective for controlling male pattern baldness with long-term daily cosmetic problems including baldness has contributed to use. Regardless of which treatment modality is chosen for male an upsurge in patient requests to generalist clinicians for pattern baldness, defining and addressing the patient’s expecta-tions regarding therapy are paramount in determining outcome.
intervention options against hair loss.
This article, intended to provide clinicians with the most current information about androgenetic alopecia in men, DHT = dihydrotestosterone; PSA = prostate-specific antigen discusses the clinical manifestations, epidemiology, psy-chosocial and physical importance, pathophysiology, diag-nosis, and management of this condition.
Management of androgenetic alopecia in men, a com- mon dermatologic condition also known as male pattern baldness, has historically been outside the scope ofthe generalist clinician’s practice—perhaps primarily be- Hair loss from androgenetic alopecia in men is progressive cause of its perceived inconsequentiality and the lack of and occurs typically in a characteristic pattern, beginning nonsurgical strategies for effective management. However, with recession of the frontal hairline and hair loss in the because of ongoing research and recent developments, an- vertex or crown and progressing to complete loss of hair drogenetic alopecia in men is recognized increasingly as a over the frontal and vertex scalp regions.4,5 In the mostsevere form of androgenetic alopecia in men, hair may bepresent only in a ring around the head in the temporal, From The Stough Hair Center, Hot Springs, Ark (D.S.); Aderans ResearchInstitute, Inc, Philadelphia, Pa (K.S.); University Hospitals, Cleveland, Ohio parietal, and occipital regions of the scalp. This progression (R.H.); Louisville Medical Center, Louisville, Ky (W.M.P.); Division of Plastic is characterized most often by the 7 categories of the Surgery, Johns Hopkins School of Medicine and Hospital, Baltimore, Md(J.E.V.); Baylor Hair Research and Treatment Center, Dallas, Tex (D.A.W.); and Hamilton-Norwood scale,6 which assists in the diagnosis Bosley, Beverly Hills, Calif (K.W.).
and monitoring of hair loss. Hair loss does not conform to This manuscript was initiated by the authors and was supported by an this progression in all individuals.
educational grant from Merck & Co, Inc; Merck & Co, Inc, was not involved inthe selection of authors, in the development or management of content, or inmanuscript preparation.
Address reprint requests and correspondence to Dow Stough, MD, TheStough Hair Center, 3633 Central Ave, Suite N, Hot Springs, AR 71913 (e-mail: dowstoughmd@cablelynx.com).
The age at onset of androgenetic alopecia in men varies, but 2005 Mayo Foundation for Medical Education and Research
occurs on average in men in their mid-20s. The prevalence Mayo Clin Proc. • October 2005;80(10):1316-1322 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Pr and severity of androgenetic alopecia in men increase di- skin cancer—possibilities that have not been established rectly with age. Because male pattern baldness depends on circulating androgens (see “Pathophysiology” section), thecondition is not observed in prepubescent children. Andro- genetic alopecia is most pervasive among middle-aged toelderly white men.7-9 Approximately 30% of white men are Normal hair growth occurs at the level of the hair follicle in affected by age 30 years, at least 50% are affected by age a 3-phased cycle: (1) anagen, a 2- to 7-year active growth 50 years, and 80% are affected by age 70 years.4 The phase during which hair is produced continuously via the incidence of androgenetic alopecia also varies with race: division and growth of specialized keratin-producing epi- white men are more likely to develop baldness than are dermal cells that surround a dermal papilla at the base of men of Asian, American Indian, and African heritage.
the hair follicle; (2) catagen, a 1- to 2-week transition and Also, the extent of hair loss often is more extensive in white involution phase, during which the hair follicle contracts as men than in men of the previously mentioned other a result of apoptosis and the hair bulb ascends toward the surface of the skin, loses its root sheaths that anchor thehair in place, and develops a club-shaped end to form a clubhair (ie, a hair in the resting state); and (3) telogen, a 5- to 12-week resting phase during which the old club hair is Most men with androgenetic alopecia experience psycho- shed. At the end of telogen, germinal cells of the hair social effects. Specifically, hair loss affects the balding follicle once again begin to grow to form a new hair bulb, individual’s feelings of attractiveness and satisfaction with which becomes the source of a new hair.4 On average, in his physical appearance (body image) and can influence the normal scalp, at least 90% of hairs are in anagen, 1% other persons’ perceptions of him.1,2 The effects of male pattern baldness on self-image and others’ perceptions are The basis of androgenetic alopecia in men is a progres- not surprising in the context of the importance of hair in the sive decrease in the density of terminal (thick and pig- sociocultural context.1,2 Hair is an important determinant of mented) hairs and a concurrent increase in density of physical attractiveness and a means of expressing individu- vellus (short, fine, nonpigmented) hairs.20 In effect, termi- ality. Throughout history, abundant hair has symbolized nal hairs are turned off and are transformed into vellus vitality, health, and virility, whereas loss or removal of hair hairs. This effect is attributed to miniaturization of the can connote subjugation, loss of individuality, impotency, hair follicle, which is associated with a substantial reduc- tion in hair diameter. Miniaturization may occur abruptly The negative effects of hair loss on body image have in 1 or a few hair cycles.21 In 1 illustrative study of biopsy been observed in several studies of androgenetic alopecia specimens from 106 men with male pattern baldness in men.10-16 Across studies, factors associated with a greater and 44 nonbalding control subjects, the ratio of terminal risk of hair loss–related psychological morbidity include to vellus hairs was 7:1 in the nonbalding scalp com- young age, not being involved in a romantic relationship, pared with 2:1 in the balding scalp.22 In male pattern strong reliance on physical appearance as a source of self- baldness, the anagen phase shortens, and the telogen esteem, and having preexisting poor self-esteem.2 Besides phase lengthens or remains the same so that hair length— affecting the balding man’s self-image, hair loss can in- which depends primarily on the duration of anagen— fluence others’ perceptions of the balding individual. In decreases.23 Eventually, the hair does not reach the skin studies comparing individuals’ initial impressions to surface. Also, the time between the telogen stage and the sketches or photographs of balding compared with non- anagen stage lengthens so that the number of scalp hairs balding men, balding men were consistently rated as less physically and socially attractive, older, less likable, and Although the mechanisms of these changes have not less virile.17-19 However, the degree to which these first been established definitively, male pattern baldness is impressions of balding men evolve over time has not been known to depend on androgens—in particular, the andro- gen dihydrotestosterone (DHT).23-25 Dihydrotestosterone is Androgenetic alopecia is not known to be life threaten- synthesized from testosterone by 5α-reductase type 1 and ing, but it can lead to physical harm. Hair protects against type 2, lipophilic enzymes found on intracellular (nuclear) sunburn, cold, and mechanical injury. Because androge- membranes.24 Type 2 5α-reductase, expressed in hair fol- netic alopecia in men involves loss of the hair’s protec- licles and other androgen-dependent tissues such as the tion of the scalp from ultraviolet light, it may increase the prostate gland, appears to be more important than type 1 in risk of sunburn and the cellular damage that underlies Mayo Clin Proc. • October 2005;80(10):1316-1322 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Pr Several lines of circumstantial evidence support the cru- like male pattern baldness, alopecia areata typically entails cial role of androgens—and DHT in particular—in male circumscribed and asymmetrical areas of baldness and can pattern baldness. First, this condition is not observed in involve the eyebrows, face, and other body parts in addi- eunuchs, who lack androgens; in individuals who lack tion to the scalp. A diagnosis of diffuse alopecia areata is functional androgen receptors; or in pseudohermaphro- suggested by findings of exclamation-point hairs, pitted dites, who lack 5α-reductase.4,25-27 The absence of baldness nails, and/or a history of periodic regrowth of hair.5 Alope- in those lacking the gene for 5α-reductase type 2 suggests a cia areata, which is much less common than male pattern necessary role for DHT. Second, the progression of andro- baldness, reportedly affects 1.7% of the US population by genetic alopecia in men is halted coincident with castration the age of 50 years.30 Other differential diagnoses include among postpubertal men.5 Third, balding scalp contains acute and chronic telogen effluvium (ie, excessive shed- excessive concentrations of 5α-reductase, DHT, and the ding of normal club hairs; may be idiopathic or associated androgen receptor.4,28,29 Finally, hair loss is mitigated or with iron deficiency, papulosquamous scalp diseases, or inhibited by finasteride, a medication that prevents the stressors) and early cicatricial alopecia (ie, hair loss arising conversion of testosterone to DHT by selectively inhibiting from the destruction of hair follicles by scarring from pro- the activity of 5α-reductase type 2.23 Although the presence cesses such as trauma, burns, lupus erythematosus, or li- of androgens and a genetic predisposition are necessary for androgenetic alopecia in men, much about the pathophysi-ology of this condition remains to be elucidated.
Androgenetic alopecia in men appears to be inherited, but the mode of inheritance is not yet understood. Hypoth- Management of male pattern baldness involves obtaining a esized modes of inheritance include a single autosomal medical history, performing a physical examination, as- dominant gene, a single pair of sex-linked factors, a domi- sessing changes in scalp hair in the context of the age and nant gene with increased or variable penetrance in men, occupation of the individual, assessing the importance of and polygenic inheritance.5,20 A family history of androge- hair loss to the patient, and working with the patient to netic alopecia may be present on either side of the family; determine the best treatment. Options for managing andro- however, the absence of such a family history does not genetic alopecia in men include doing nothing and accept- ing the cosmetic outcome (the “wait and see” approach),pharmacotherapy, hair transplantation, and cosmetic aids.
Hair loss is progressive and does not improve or reverse Male pattern baldness is diagnosed primarily on the basisof history and physical examination.5 Men with a history of progressive hair loss that follows the pattern defined by the Two US Food and Drug Administration–approved pharma- Hamilton-Norwood scale are highly likely to have male cotherapies—minoxidil and finasteride—are available for treatment of male pattern baldness. These medications, Biopsies can be used as diagnostic aids but seldom are which differ in mechanism of action and route of adminis- required for diagnosis. Histopathologic changes character- tration, are given as monotherapy or as combination istic of male pattern baldness include a progressive in- therapy, although few clinical studies of combination crease in the density of vellus hairs (vellus hair shafts therapy have been published to date. These drugs often are are ≤0.03 mm in diameter and thinner than the follicle’s prescribed for patients undergoing hair-restoration surgery inner root sheath), a decrease in the density of terminal to reduce the amount of transplanted hair required to meet hairs (terminal hair shafts are >0.03 mm in diameter and the patient’s objectives and to help the patient maintain a thicker than the follicle’s inner root sheath), and a decrease relatively consistent and natural appearance. Although in the ratio of terminal to vellus hair from 7:1 to approxi- minoxidil and finasteride both retard or stop hair loss and mately 2:1.5,9 These changes may be observed in the ab- stimulate some hair regrowth, neither medication restores sence of an abnormal total number of hairs per unit area.
all lost hair or reverses complete baldness. No well-con- Androgenetic alopecia is not considered to be an inflamma- trolled study comparing minoxidil and finasteride has been tory condition; however, superficial perifollicular infiltrate published to date. In a randomized study in which 99 patients treated with finasteride or minoxidil were moni- The differential diagnosis of male pattern baldness in- tored for up to 24 months, both agents appeared to be cludes diffuse alopecia areata—recurrent, nonscarring hair similarly effective for stopping the progression of androge- loss that may be associated with autoimmune disease. Un- Mayo Clin Proc. • October 2005;80(10):1316-1322 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Pr Minoxidil. Initially introduced in the 1970s as a sys-
DHT concentrations by approximately 60% to 70%.37 temic treatment of hypertension, minoxidil now is mar- Finasteride may inhibit or reverse miniaturization of hair keted also as topical 2% and 5% solutions for androgenetic follicles as shown by a trend toward improvement in the alopecia in men and women.32 Minoxidil is a potassium terminal-to-vellus ratio in a scalp biopsy study.38 channel opener, and its mechanism of action in male pat- The clinical efficacy of finasteride has been documented tern baldness is unknown. Minoxidil appears to increase in well-controlled clinical trials that monitored men with the duration of the anagen phase, and its angiogenic effects male pattern baldness for up to 5 years. In 2 double-blind reverse miniaturization of hair follicles. In placebo-con- placebo-controlled clinical trials that were continued as 4 trolled clinical studies, minoxidil slowed hair loss and in- consecutive 1-year, placebo-controlled extension trials (for creased hair density, measured by target-area hair counts, a total of up to 5 years of observation), 18- to 41-year-old expert panel review of global photographs, and hair men with primarily vertex hair loss received daily treat- weight.33,34 Growth of hair appears to peak approximately 4 ment with 1 mg of finasteride or placebo.39-41 Compared months after initiation of therapy. The 5% solution is asso- with placebo, finasteride slowed hair loss and increased ciated with an earlier and more robust response than the 2% hair density and length across several efficacy measures.
solution for male pattern baldness. In a randomized, Finasteride was associated with increased target-area hair double-blind, placebo-controlled study in which patients counts (16.9/cm2 vs –4.1/cm2 with placebo at 1 year) and applied 5% minoxidil (n=157), 2% minoxidil (n=158), or higher incidence of increased hair growth (at 1 year, 48% placebo (n=78) twice daily, hair density improved more increase with finasteride vs 7% increase with placebo; at 2 with active treatment than placebo. In addition, androge- years, 66% increase with finasteride vs 7% increase with netic alopecia improved more with the 5% solution com- placebo), effects that were sustained throughout the 5-year pared with the 2% solution, reflected in target-area hair treatment period. By photographic assessment, improve- count increases after 48 weeks of treatment (18.6/cm2 for ment in hair growth or no visible hair loss was observed in the 5% solution, 12.7/cm2 for the 2% solution, and 3.9/cm2 90% of men treated with finasteride (48% improvement; for placebo) and in expert panel review of global photo- 42% no visible loss) compared with 25% of placebo- graphs after 1 year (increased growth in 57.9% of men with treated patients (6% improvement; 19% no visible loss).
the 5% solution, 40.8% of men with the 2% solution, and Growth of hair did not appear to plateau until approxi- mately 1 to 2 years after initiation of therapy. Visible To maximize efficacy, minoxidil should be applied worsening in scalp hair was reported for 10% of finas- evenly to the entire affected area of the scalp. Patients teride-treated patients compared with 75% of placebo- should avoid wetting the scalp for at least 1 hour after treated patients after 5 years of treatment. At the end of this minoxidil administration to allow the drug sufficient time 5-year period, hair counts improved in a 1-inch-diameter to be absorbed; also, patients should apply minoxidil be- area of scalp hair loss (from a baseline of 876 hairs) by 277 fore any use of hair gel or hair spray so that absorption is hairs with finasteride compared with placebo; furthermore, not affected.9 Minoxidil must be applied daily to maintain 65% of finasteride-treated patients compared with 0% of effectiveness. If treatment is discontinued over a period of placebo-treated patients had increased hair count compared a few months, the scalp appears to revert to the state that it with baseline. Finasteride also was effective vs placebo for would have been in without pharmacotherapy.35 slowing hair loss and increasing hair density in a 1-year Generally, minoxidil is well tolerated with long-term double-blind study of finasteride in men with predomi- daily use. Adverse events are primarily dermatologic and include irritant contact dermatitis and, less often, allergic These objective improvements were associated with in- contact dermatitis.36 Transient and self-limiting telogen ef- creased patient satisfaction and body image.23 Most fluvium may begin approximately 3 to 5 weeks after initia- finasteride-treated patients reported that they were satisfied tion of treatment. Patients should be informed about the with the overall appearance of their scalp at the end of 5 possibility of temporary telogen effluvium and advised to years of treatment. Finasteride-treated men rated their hair growth and satisfaction with their appearance more posi- Finasteride. Initially introduced in a 5-mg dose for
tively than did placebo-treated men.
treatment of benign prostatic hyperplasia, finasteride is Baldness progresses with discontinuation of finasteride now marketed in a 1-mg dose for treatment of male pattern as DHT levels return to pretreatment levels. Therefore, to baldness. Finasteride selectively inhibits the type 2 5α- maintain therapeutic benefits, finasteride is taken long- reductase isoenzyme responsible for converting testoster- one to DHT, the putative hormonal modulator of androge- Finasteride predictably reduces total serum prostate- netic alopecia in men. Finasteride reduces serum and scalp specific antigen (PSA), an effect that appears to plateau Mayo Clin Proc. • October 2005;80(10):1316-1322 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Pr after approximately 6 months of therapy.43 By multiplying tered in attempting to achieve the objective in the previous the patient’s PSA level by 2, the utility of serum PSA as a procedures and to integrate the chief concerns of the patient screening tool for prostate cancer is preserved in men tak- Hair transplantation entails the transfer of hair follicles Finasteride generally is well tolerated with long-term from the back or sides of the head, where hair grows daily use. Its adverse event profile is comparable to that of independently of androgens, to balding areas.3 Many pa- placebo except for sexual adverse effects, which were re- tients who undergo hair transplantation can receive a suffi- ported slightly more frequently with finasteride use than ciently dense transplant in 1 or 2 surgical sessions. Ex- with placebo over 1 year (decreased libido, 1.8% vs 1.3%; tremely natural and aesthetically pleasing results can be erectile dysfunction, 1.3% vs 0.7%; ejaculatory disorders, achieved with today’s techniques.44,45 Results are approxi- 1.2% vs 0.7%).41 Sexual adverse effects of finasteride often mately 70% evident by 5 to 6 months after surgery and diminish or resolve with continued treatment and reverse can vary, depending on the extensiveness of presurgical on discontinuation of treatment. The incidence of each of hair loss, the density of transplanted grafts per unit area, the previously cited sexual adverse effects for 1 year of patient expectations, and the surgeon’s skill. Limitations treatment decreased to 0.3% or less with continued treat- of surgical approaches include cost and scarring.3,5 A ment with finasteride for up to 5 years.41 density exceeding 40 follicular units/cm2 in the donor In the Prostate Cancer Prevention Trial, a randomized, area typically is required. Continued hair loss after sur- double-blind, placebo-controlled trial in which 18,882 men gery is normal because of the progressive nature of hair aged 55 years or older were randomized to treatment with loss. The need for repeated surgeries is common, espe- finasteride (5 mg/d) or placebo for 7 years, finasteride cially in transplantation in the crown area. To optimize appeared to prevent or delay onset of prostate cancer.44 results, pharmacotherapy is recommended in conjunction Prostate cancer was detected in 803 (18.4%) of the 4368 with hair transplantation to maintain the resident non- men in the finasteride group and 1147 (24.4%) of the 4692 men in the placebo group. Over the 7-year period, the Scalp Reduction. In scalp reduction, areas of balding
reduction in prevalence of prostate cancer with finasteride scalp are removed to bring areas of hair-containing scalp relative to placebo was 24.8%. Whether the 1-mg dose of closer to one another. A valuable tool in some cases, scalp finasteride used in the treatment of male pattern baldness reduction is performed with limited frequency. Limitations has a similar effect is unknown. Also, the degree to which of scalp reduction include potential widening of scars over the results of the study can be generalized to the male time and the need for repeated scalp reductions because of population at large has not been determined.
the progressive nature of hair loss. However, in a carefullyselected subset of patients with androgenetic alopecia, scalp reduction surgery can be beneficial.
Hair Transplantation. Surgical techniques, primarily
hair transplantation, have been used for nearly half a cen- tury to manage male pattern baldness. Hair restoration Cosmetic aids including wigs and hairpieces to hide hair surgical techniques and technology have advanced particu- loss can be used alone or in conjunction with surgery or larly rapidly over the past 2 decades. Because of these pharmacotherapy. Wigs and hair systems today appear advances, results from surgical hair restoration appear much more natural and weigh much less than in the past.
much more natural and pleasing than in past decades; vi- Pigmented powders, lotions, and hair sprays can be used sual evidence that a surgical procedure was performed is to assist in camouflaging hair loss by adhering to existing not apparent to the casual observer. In contrast, surgical hair to create the illusion of increased density or by de- procedures in previous years could not provide these same creasing the color contrast between the hair and the un- advantages; today, unnatural results remain in patients who derlying scalp. However, they do not treat the underlying underwent procedures performed with older techniques.
These patients often bear the physical and emotional scarsof unnatural hair appearance and distrust the field of hair restoration surgery. The challenge for the hair restoration surgeon is to provide a level of expertise and honesty tothese patients to restore their appearance and self-confi- Regardless of which treatment modality is chosen for male dence. Accurate assessment of the hair restoration problem pattern baldness, defining and managing the patient’s ex- is paramount to designing the best possible solution for the pectations regarding therapy is paramount in determining patient. It is important to determine the problems encoun- outcomes. When consulted by an individual concerned Mayo Clin Proc. • October 2005;80(10):1316-1322 • www.mayoclinicproceedings.com For personal use. Mass reproduce only with permission from Mayo Clinic Pr about male pattern baldness, it is important to determine 5. Feinstein R. Androgenetic alopecia. Available at: www.emedicine.com/
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