家 庭 醫 業 1 2 3 3,4,5 3,4 學 頭 髮 生 長 循 環 (Androgenetic Alopecia) (nonscaring hair loss) (Caucasian) 30 30% 50 50% 70 80% [1] (Asian) (African-American) 5 [2] 1 衛 生 福 利 部 屏 東 醫 院 家 庭 醫 學 科 2 台 北 榮 民 總 醫 院 皮 膚 科 3 高 雄 醫 學 大 學 附 設 中 和 紀 念 醫 院 家 庭 醫 學 科 4 高 雄 醫 學 大 學 附 設 中 和 紀 念 醫 院 社 區 醫 學 部 5 高 雄 醫 學 大 學 家 庭 醫 學 科 Androgenetic Alopecia, hair loss, Finasteride, Minoxidil (Anagen) 2-6 (Catagen) 2-3 (Telogen) 2-3 [3] 病 理 機 轉 (androgens) [1] =12:1 5:1 follicular miniaturization 320 家 庭 醫 學 與 基 層 醫 療 第 十 一 期
androgen receptor androgen insensitivity syndrome (androgen receptor ) [4] Dihydrotestosterone (DHT) [5] DHT (testosterone) androgen receptor 7 DHT 5-alpha reductase 5-alpha reductase 2 Type I (sebaceous glands) (dermal papillae cells) (follicular keratinocytes) Type II (Outer root sheath of hair follicles) (epididymis) (vas deferens) (seminal vesicles) (prostate) 5-alpha reductase type 2 gene [6] Follicular miniaturization (dermal papilla) androgen receptor transforming growth factorbeta gene [7] DHT 5 alpha-reductase androgen receptor [8] [9] polygenic with variable penetrance [10] X chromosome Androgen receptor (AR)/EDAR2 locus [11], chromosome 20p11 PAX1/FOXA2 locus [12] chromosome 7p21.1 HDAC9 [13] 臨 床 表 徵 與 診 斷 The Hamilton Norwood classification 7 ( ) ( ) follicular miniaturization ( cicatrical alopecia) 治 療 方 式 家 庭 醫 學 與 基 層 醫 療 第 十 一 期 321
圖 一 資 料 來 源 : Norwood OT: Male pattern baldness: classification and incidence. South Med J 1975; 68: 1359 1365. minoxidil Finasteride 1. Finasteride: Finasteride 5-alphareductase type II enzyme DHT [14] 1mg/ day Finasteride DHT level 60% [15] androgen receptor [14] meta-analysis 322 家 庭 醫 學 與 基 層 醫 療 第 十 一 期
placebo-controlled randomized trials Finasteride 6-12 9% 48 24% [16] 1553 18-41 Finasteride (1 mg/day) Finasteride Finasteride 2 2/3 7% [17] Finasteride 1 6-9 Finasteride Finasteride meta-analysis 1.5% [18] 71 26 Finasteride 28 20% 6 [19] Finasteride Finasteride prostate specific antigen (PSA) Finasteride PSA [20] finasteride highgrade prostate cancer [21] 2. Minoxidil: Minoxidil 2% solution, 5% solution 5% foam 5% foam propylene glycol [22] Minoxidil [23] Minoxidil vasodilator VEGF(vascular endothelial growth factor) (dermal papilla) [24] 352 5% solution 2% solution 48 [25] 5% solution 5% foam Minoxidil 家 庭 醫 學 與 基 層 醫 療 第 十 一 期 323
FDA (Low-level laser light) androgenindependent androgendependent 結 論 FDA Monixidil Finasteride 參 考 資 料 1. Ellis JA, Sinclair R, Harrap SB: Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med 2002; 4: 1-11. 2. Birch MP, Messenger AG: Genetic factors predispose to balding and non-balding in men. Eur J Dermatol 2001; 11: 309-14. 3. Paus R, Cotsarelis G: The biology of hair follicles. N Engl J Med 1999; 341: 491-7. 4. Tadokoro-Cuccaro R, Hughes IA: Curr Opin Endocrinol Diabetes Obes. 2014; 21: 499-503. 5. Kaufman KD: Androgens and alopecia. Mol Cell Endocrinol 2002; 198: 89-95. 6. Imperato-McGinley J, Zhu YS: Androgens and male physiology the syndrome of 5 alphareductase-2 deficiency. Mol Cell Endocrinol 2002; 198: 51-9. 7. Hamada K, Randall VA: Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness. Br J Dermatol 2006; 154: 609-18. 8. Vierhapper H, Nowotny P, Maier H, Maldhausl W: Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001; 86: 5762-4. 9. Schmidt JB, Lindmaier A, Spona J: Hormonal parameters in androgenetic hair loss in the male. Dermatologica 1991; 182: 214-7. 10. Bergfeld WF: Androgenetic alopecia: an autosomal dominant disorder. AmJ Med 1995; 98: 95-8S. 11. Hillmer AM, Hanneken S, Ritzmann S, et al: Genetic variation in the human androgenreceptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet 2005; 77: 140-8. 12. Hillmer AM, Brockschmidt FF, Hanneken D, et al: Susceptibility variants for male-pattern baldness on chromosome 20p11. Nat Genet 2008; 40: 1279-81. 13. Brockschmidt FF, Heilmann D, Ellis JA, et al: Susceptibility variants on chromosome 7p21.1 324 家 庭 醫 學 與 基 層 醫 療 第 十 一 期
suggest HDAC9 as a new candidate gene for male-pattern baldness. Br J Dermatol 2011; 165: 1293-302. 14. Rittmaster RS: Finasteride. N Engl J Med 1994; 330: 120-125. 15. Prince VH: Treatment of hair loss. N Engl J Med 1999; 341: 964-73. 16. Mella JM, Perret MC, Manzotti M, et al: Efficacy and safety of finasteride therapy for androgenetic alopecia: a systemic review. Arch Dermatol 2010; 146: 1141-50. 17. Kaufman KD, Olsen EA, Whiting D, et al: Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 1998; 39: 578-89. 18. Olsen EA, Whiting DA, Savin R, et al: Global photographic assessment of men aged 18 to 60 years with male pattern hair loss receiving finasteride 1mg or placebo. J Am Acad Dermatol 2012; 67: 379-86. 19. Irwig MS, Kolukula S: Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med 2011; 8: 1747-53. 20. D Amico AV, Roehrborn CG: Effect of 1 mg/ day finasteride on concentrations of serum prostate-specfic antigen in men with androgenic alopecia: a randomized controlled trial. Lancet Oncol 2007; 8: 21-5. 21. Ian M. Thompson, Phyllis J. Goodman, Catherine M. Tangen, et al: Long-Term Survival of Participants in the Prostate Cancer Prevention Trial. N Engl J Med. 2013; 369: 603-10. 22. Olsen EA, Whiting D, Bergfeld W, et al: A multicenter, randomized, placebo-controlled, double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol 2007; 57: 767-74. 23. Messenger AG, Rundegren J: Minoxidil: mechanisms of action on hair growth. Br J Dermatol 2004; 150: 186-94. 24. Lachgar S, Charveron M, Gall Y, Bonafe JL: Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells. Br J Dermatol 1998; 138: 407-11. 25. De Villez RL: Topical minoxidil therapy in hereditary androgenetic alopecia. Arch Dermatol 1985; 121: 197-202. 家 庭 醫 學 與 基 層 醫 療 第 十 一 期 325