Тіе Modern treatment of androgenetic alopecia

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Abstract

Androgenetic alopecia (AGA) is the most common reason for hair loss. Its frequency in Caucasian population is up to 80% in men and 42% in women. Current gold standard for AGA treatment includes minoxidil and/or finasteride. Both drugs have moderate treatment efficacy and can cause significant side effects. Minoxidil is the only option for treatment of AGA in women since finasteride has no efficacy. This review considers actual concepts of molecular mechanisms of pathogenesis and current treatment options of AGA with their limitations and shortcomings. Current state and perspectives of novel approaches to AGA treatment, potentially more effective and safe than minoxidil and finasteride, are described. The review discusses growth factors and cytokines, topical 5-alpha-reductase inhibitors, androgen receptor antagonists, prostaglandin analogs and antagonists, Wnt signaling activators and platelet-rich plasma injections.

About the authors

V. K. Karnaukhov

Lomonosov Moscow State University

Author for correspondence.
Email: vadim-karnaukhov@mail.ru
Russian Federation

A. A. Lukyanova

Shkola stilistov Persona

Email: noemail@neicon.ru
Russian Federation

M. I. Lukashina

Federal State Budget Institution of Sciences Institute of Gene Biology, Russian Academy of Sciences; The Russian National Research Medical University named after N.I. Pirogov

Email: noemail@neicon.ru
Russian Federation

E. S. Vorobeva

Federal State Budget Institution of Sciences Institute of Gene Biology, Russian Academy of Sciences

Email: noemail@neicon.ru
Russian Federation

I. M. Afanasov

OOO ”DzhiJef Grupp”

Email: noemail@neicon.ru
Russian Federation

References

  1. Sinclair R. Male pattern androgenetic alopecia. Bmj 1998; 317 (7162): 865-869.
  2. Blume-Peytavi U., Blumeyer A., Tosti A., et al. S1 guideline for diagnostic evaluation in androgenetic alopecia in men, women and adolescents. Br J Dermatol 2011; 164 (1): 5-15.
  3. Yip L., Rufaut N., Sinclair R. Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know. Australas J Dermatol 2011; 52 (2): 81-88.
  4. Heilmann-Heimbach S., Hochfeld L. M., Paus R., Nöthen M. M. Hunting the genes in male-pattern alopecia: how important are they, how close are we and what will they tell us? Exp Dermatol 2016.
  5. Heilmann S., Brockschmidt F. F., Hillmer A. M., et al. Evidence for a polygenic contribution to androgenetic alopecia. Br J Dermatol 2013; 169 (4): 927-930.
  6. Olsen E. A. Female pattern hair loss. J Am Acad Dermatol 2001; 45 (3): S70-S80.
  7. Mesinkovska N. A., Bergfeld W. F. Hair: What is New in Diagnosis and Management?: Female Pattern Hair Loss Update: Diagnosis and Treatment. Dermatol Clin 2013; 31 (1): 119-127.
  8. Hunt N., McHale S. The psychological impact of alopecia. Br Med J 2005; 7522: 951.
  9. Cash T. F. The psychology of hair loss and its implications for patient care. Clin Dermatol 2001; 19 (2): 161-166.
  10. Garza L. A., Yang C. C., Zhao T., et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest 2011; 121 (2): 613-622.
  11. Kelly Y., Blanco A., Tosti A. Androgenetic Alopecia: An Update of Treatment Options. Drugs 2016; 76 (14): 1349-1364.
  12. Rogers N. E., Avram M. R. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol 2008; 59 (4): 547-566.
  13. Friedman E. S., Friedman P. M., Cohen D. E., Washenik K. Allergic contact dermatitis to topical minoxidil solution: etiology and treatment. J Am Acad Dermatol 2002; 46 (2): 309-312.
  14. Georgala S., Befon A., Maniatopoulou E., Georgala C. Topical use of minoxidil in children and systemic side effects. Dermatology 2006; 214 (1): 101-102.
  15. Lucky A. W., Piacquadio D. J., Ditre C. M., et al. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol 2004; 50 (4): 541-553.
  16. Goren A., Castano J. A., McCoy J., Bermudez F., Lotti T. Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia. Dermatol Ther 2014; 27 (3): 171-173.
  17. Roberts J., Desai N., McCoy J., Goren A. Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia. Dermatol Ther 2014; 27 (4): 252-254.
  18. Messenger A. G., Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol 2004; 150 (2): 186-194.
  19. Rossi A., Cantisani C., Melis L., Iorio A., Scali E., Calvieri S. Minoxidil use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov 2012; 6 (2): 130-136.
  20. Michelet J.-F., Commo S., Billoni N., Mahe Y. F., Bernard B. A. Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect. J Invest Dermatol 1997;108 (2): 205-209.
  21. Olsen E. A., 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 (5): 767-774.
  22. Blumeyer A., Tosti A., Messenger A., et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. JDDG 2011; 9 (6): 1-57.
  23. Hillmann K., Garcia Bartels N., Kottner J., Stroux A., Canfield D., Blume-Peytavi U. A Single-Centre, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Investigate the Efficacy and Safety of Minoxidil Topical Foam in Frontotemporal and Vertex Androgenetic Alopecia in Men. Skin Pharmacol Physiol 2015; 28 (5): 236-244.
  24. Blume-Peytavi U., Hillmann K., Dietz E., Canfield D., Bartels N. G. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women. J Am Acad Dermatol 2011; 65 (6): 1126-1134.
  25. Olsen E. A., Dunlap F. E., 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 men. J Am Acad Dermatol 2002; 47 (3): 377-385.
  26. Olsen E. A., Weiner M. S. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. J Am Acad Dermatol 1987; 17 (1): 97-101.
  27. Azzouni F., Zeitouni N., Mohler J. Role of 5a-reductase inhibitors in androgen-stimulated skin disorders. J drugs dermatology JDD 2013; 12 (2): e30-e35.
  28. Arca E., Aţikgoz G., Taştan H. B., Köse O., Kurum-lu Z. An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia. Dermatology 2004; 209 (2): 117-125.
  29. Cilotti A., Danza G., Serio M. Clinical application of 5a-reductase inhibitors. J Endocrinol Invest 2001; 24 (3): 199-203.
  30. Drake L., Hordinsky M., Fiedler V., et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 1999; 41 (4): 550-554.
  31. Irwig M. S., Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med 2011; 8 (6): 1747-1753.
  32. I rwig M. S. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry 2012; 73 (9): 1220-1223.
  33. Caruso D., Abbiati F., Giatti S., et al. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma. J Steroid Biochem Mol Biol 2015; 146: 74-79.
  34. Schüle C., Nothdurfter C., Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol 2014; 113: 79-87.
  35. Rahimi-Ardabili B., Pourandarjani R., Habibollahi P., Mualeki A. Finasteride induced depression: a prospective study. BMC Pharmacol Toxicol 2006; 6 (1): 7.
  36. Ferrando J., Grimalt R., Alsina M., Bulla F., Manasievska E. Unilateral gynecomastia induced by treatment with 1 mg of oral finasteride. Arch Dermatol 2002; 138 (4): 543-544.
  37. Ramot Y., Czarnowicki T., Zlotogorski A. Finasteride induced Gynecomastia: Case report and Review of the Literature. Int J Trichology 2009; 1 (1):27.
  38. Price V. H., Roberts J. L., Hordinsky M., et al. Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. J Am Acad Dermatol 2000; 43 (5): 768-776.
  39. Bowman C. J., Barlow N. J., Turner K. J., Wallace D. G., Foster P. M. D. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol Sci 2003; 74 (2): 393-406.
  40. Investigators WG for the WHI. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. Jama 2002; 288 (3): 321-333.
  41. Gupta A. K., Charrette A. The efficacy and safety of 5a-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride. J Dermatolog Treat 2014; 25 (2): 156-161.
  42. Andriole G. L., Kirby R. Safety and tolerability of the dual 5a-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003; 44 (1): 82-88.
  43. Jain R., De-Eknamkul W. Potential targets in the discovery of new hair growth promoters for androgenic alopecia. Expert Opin Ther Targets 2014; 18 (7): 787-806.
  44. Botchkarev V. A., Paus R. Molecular biology of hair morphogenesis: development and cycling. J Exp Zool Part B Mol Dev Evol 2003; 298 (1): 164-180.
  45. Yano K., Brown L. F., Detmar M. Control of hair growth and follicle size by VEGF-mediated angio-genesis. J Clin Invest 2001; 107 (4): 409-417.
  46. Lachgar S., Charveron M., Ceruti I. Distribution of VEGF mRNA indifferent hair follicle stages by fluorescence in situ hybridization combined with confocal laser microscopy. Hair Res next Millenn 1996: 407-412.
  47. Lachgar S., Charveron M., Gall Y., Bonafe J. L. Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells. Br J Dermatol 1998; 138 (3): 407-411.
  48. Danilenko D. M., Ring B. D., Pierce G. F. Growth factors and cytokines in hair follicle development and cycling: recent insights from animal models and the potentials for clinical therapy. Mol Med Today 1996; 2 (11): 460-467.
  49. Tang L., Bernardo O., Bolduc C., Lui H., Madani S., Shapiro J. The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia. J Am Acad Dermatol 2003; 49 (2): 229- 233.
  50. Weger N., Schlake T. Igf-I signalling controls the hair growth cycle and the differentiation of hair shafts. J Invest Dermatol 2005; 125 (5): 873- 882.
  51. Castro R. F., Azzalis L. A., Feder D., et al. Safety and efficacy analysis of liposomal insulin-like growth factor-1 in a fluid gel formulation for hair-loss treatment in a hamster model 2012; (001): 1-4.
  52. Gnann L. A., Castro R. F., Azzalis L. A., et al. Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model 2013: 2-6.
  53. Tsuboi R. Growth factors and hair growth. Korean J Investig Dermatology 1997; 4 (2): 103-108.
  54. Danilenko D. M., Ring B. D., Yanagihara D., et al. Keratinocyte Growth Factor Is an Important Endogenous Mediator of Hair Follicle Growth, Development, and Differentiation Normalization of the nu / nu Follicular Differentiation Defect and Amelioration of Chemotherapy-Induced Alopecia. Am J Pathol 1995; 147 (1): 145-154.
  55. Jang J.-H. Stimulation of human hair growth by the recombinant human keratinocyte growth factor-2 (KGF-2). Biotechnol Lett 2005; 27 (11): 749-752.
  56. Jindo T., Tsuboi R., Imai R., Takamori K., Rubin J. S., Ogawa H. The effect of hepatocyte growth factor/scatter factor on human hair follicle growth. J Dermatol Sci 1995; 10 (3): 229-232.
  57. Shimaoka S., Tsuboi R., Jindo T., et al. Hepatocyte growth factor/scatter factor expressed in follicular papilla cells stimulates human hair growth in vitro. J Cell Physiol 1995; 165 (2): 333-338.
  58. Gay D., Kwon O., Zhang Z., et al. Fgf9 from dermal [gamma][delta] T cells induces hair follicle neogenesis after wounding. Nat Med 2013; 19 (7): 916-923.
  59. Yim E, Nole KLB, Tosti A. 5a-Reductase inhibitors in androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes 2014; 21 (6): 493-498.
  60. Caserini M., Radicioni M., Leuratti C., Annoni O., Palmieri R. A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels in healthy male volunteers. Int J Clin Pharmacol Ther 2014; 52 (10): 842-849.
  61. Caserini M., Radicioni M., Leuratti C., Terragni E., Iorizzo M., Palmieri R. Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia. Int J Clin Pharmacol Ther 2016; 54 (1): 19-27.
  62. Kumar R., Singh B., Bakshi G., Katare O. P. Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation. Pharm Dev Technol 2007; 12 (6): 591-601.
  63. Madheswaran T., Baskaran R., Thapa R. K., et al. Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery. AAPS PharmSciTech 2013; 14 (1): 45-52.
  64. Caon T., Porto L. C., Granada A., et al. Chitosan-decorated polystyrene-b-poly (acrylic acid) polymersomes as novel carriers for topical delivery of finasteride. Eur J Pharm Sci 2014; 52: 165-172.
  65. Yip L., Sinclair R. D. Antiandrogen therapy for androgenetic alopecia. Expert Rev Dermatol 2006; 1 (2): 261-269.
  66. Johnstone M. A. Hypertrichosis and increased pigmentation of eyelashes and adjacent hair in the region of the ipsilateral eyelids of patients treated with unilateral topical latanoprost. Am J Ophthalmol 1997; 124 (4): 544-547.
  67. Tauchi M., Fuchs T. A., Kellenberger A. J., Woodward D. F., Paus R., Lütjen-Drecoll E. Characterization of an in vivo model for the study of eyelash biology and trichomegaly: mouse eyelash morphology, development, growth cycle, and anagen prolongation by bimatoprost. Br J Dermatol 2010; 162 (6): 1186-1197.
  68. Blume-Peytavi U., Lönnfors S., Hillmann K., Bartels N. G. A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia. J Am Acad Dermatol 2012; 66 (5): 794-800.
  69. Smith S., Fagien S., Whitcup S. M., et al. Eyelash growth in subjects treated with bimatoprost: a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study. J Am Acad Dermatol 2012; 66 (5): 801-806.
  70. Khidhir K. G., Woodward D. F., Farjo N. P., et al. The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias. FASEB J 2013; 27 (2): 557-567.
  71. Emer J. J., Stevenson M. L., Markowitz O. Novel treatment of female-pattern androgenetic alopecia with injected bimatoprost 0.03% solution. J drugs dermatology JDD 2011; 10 (7): 795-798.
  72. Garza L. A., Liu Y., Yang Z., et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med 2012; 4 (126): 126-134
  73. Chen D., Jarrell A., Guo C., Lang R., Atit R. Dermal а-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development 2012; 139 (8): 1522-1533.
  74. Andl T., Reddy S. T., Gaddapara T., Millar S. E. WNT Signals Are Required for the Initiation of Hair Follicle Development. Dev Cell 2002; 2 (5): 643-653.
  75. Ito M., Yang Z., Andl T, et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 2007; 447 (7142): 316- 320.
  76. Jo S. J., Shin H., Park Y. W., et al. Topical valproic acid increases the hair count in male patients with androgenetic alopecia: a randomized, comparative, clinical feasibility study using phototrichogram analysis. J Dermatol 2014; 41 (4): 285-291.
  77. Li Z. J., Choi H., Choi D., et al. Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth. Dermatologic Surg 2012; 38 (7): 1040-1046.
  78. Eppley B. L., Woodell J. E., Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114 (6): 1502-1508.
  79. Uebel C. O., da Silva J. B., Cantarelli D., Martins P. The role of platelet plasma growth factors in male pattern baldness surgery. Plast Reconstr Surg 2006; 118 (6): 1458-1466.
  80. Gentile P., Garcovich S., Bielli A., Scioli M. G., Orlandi A., Cervelli V. The effect of platelet-rich plasma in hair regrowth: a randomized placebo-controlled trial. Stem Cells Transl Med 2015; 4 (11): 1317-1323.
  81. Nusbaum A. G., Tosti A. Commentary on a Randomized Placebo-Controlled, Double-Blind, Half-Head Study to Assess the Efficacy of Platelet-Rich Plasma on the Treatment of Androgenetic Alopecia. Dermatologic Surg 2016; 42 (4): 498-499.
  82. Cervelli V., Garcovich S., Bielli A., et al. The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation. Biomed Res Int 2014; 2014.
  83. Schiavone G., Raskovic D., Greco J., Abeni D Platelet-rich plasma for androgenetic alopecia a pilot study. Dermatologic Surg 2014; 40 (9): 1010-1019.
  84. Navarro M. R., Asin M., Martinez M. A., et al. Management of androgenetic alopecia: a comparative clinical study between plasma rich in growth factors and topical minoxidil. Eur J Plast Surg 2016; 39 (3): 173-180.

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Copyright (c) 2017 Karnaukhov V.K., Lukyanova A.A., Lukashina M.I., Vorobeva E.S., Afanasov I.M.

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