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通讯作者:

李吉(1978-),男,湖南岳阳人,博士生导师,主要从事损容性皮肤病(脱发性疾病、玫瑰痤疮及皮肤衰老与再生)的临床与科硏工作。E-mail:liji_xy@csu.edu.cn

中图分类号:R758.71,R-1

文献标识码:A

文章编号:2096-8965(2021)02-0086-05

DOI:10.12287/j.issn.2096-8965.20210213

参考文献 1
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参考文献 2
LEE W S,RO B I,HONG S P,et al.A new classification of pattern hair loss that is universal for men and women:basic and specific(BASP)classification[J].J Am Acad Dermatol,2007,57(1):37-46.
参考文献 3
KANTI V,MESSENGER A,DOBOS G,et al.Evidencebased(S3)guideline for the treatment of androgenetic alopecia in women and in men-short version[J].J Eur Acad Dermatol Venereol,2018,32(1):11-22.
参考文献 4
GUPTA A K,CHARRETTE A.The efficacy and safety of 5 alpha-reductase inhibitors in androgenetic alopecia:a network meta-analysis and benefit-risk assessment of finasteride and dutasteride[J].J Dermatolog Treat,2014,25(2):156-161.
参考文献 5
HABER R S,GUPTA A K,EPSTEIN E,et al.Finasteride for androgenetic alopecia is not associated with sexual dysfunction:a survey-based,single-centre,controlled study[J].J Eur Acad Dermatol Venereol,2019,33(7):1393-1397.
参考文献 6
HAJHEYDARI Z,AKBARI J,SAEEDI M,et al.Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia[J].Indian J Dermatol Venereol Leprol,2009,75(1):47-51.
参考文献 7
BURKE B M,CUNLIFFE W J.Oral spironolactone therapy for female patients with acne,hirsutism or androgenic alopecia[J].Br J Dermatol,1985,112(1):124-125.
参考文献 8
CAMACHO-MARTINEZ F M.Hair loss in women[J].Semin Cutan Med Surg,2009,28(1):19-32.
参考文献 9
RATHNAYAKE D,SINCLAIR R.Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss[J].Dermatol Clin,2010,28(3):611-618.
参考文献 10
SINCLAIR R,WEWERINKE M,JOLLEY D.Treatment of female pattern hair loss with oral antiandrogens[J].Br J Dermatol,2005,152(3):466-473.
参考文献 11
ROSSI A,CANTISANI C,MELIS L,et al.Minoxidil use in dermatology,side effects and recent patents[J].Recent Pat Inflamm Allergy Drug Discov,2012,6(2):130-136.
参考文献 12
SHAPIRO J,HO A,SUKHDEO K,et al.Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1298-1303.
参考文献 13
DUBIN D P,LIN M J,LEIGHT H M,et al.The effect of platelet-rich plasma on female androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1294-1297.
参考文献 14
SHON U,KIM M H,LEE D Y,et al.The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism[J].J Am Acad Dermatol,2020,83(6):1838-1839.
参考文献 15
TAK Y J,LEE S Y,CHO A R,et al.A randomized,double-blind,vehicle-controlled clinical study of hair regeneration using adipose-derived stem cell constituent extract in androgenetic alopecia[J].Stem Cells Transl Med,2020,9(8):839-849.
参考文献 16
ADIL A,GODWIN M.The effectiveness of treatments for androgenetic alopecia:a systematic review and metaanalysis[J].J Am Acad Dermatol,2017,77(1):136-141.
参考文献 17
RAMOS P M,MCCOY J,WAMBIER C,et al.Novel topical booster enhances follicular sulfotransferase activity in patients with androgenetic alopecia:a new strategy to improve minoxidil response[J].J Eur Acad Dermatol Venereol,2020,34(12):e799-e800.
参考文献 18
BARAT T,ABDOLLAHIMAJD F,DADKHAHFAR S,et al.Evaluation of the efficacy and safety of cow placenta extract lotion versus minoxidil 2% in the treatment of female pattern androgenetic alopecia[J].Int J Womens Dermatol,2020,6(4):318-321.
参考文献 19
KERKEMEYER K L,TRINDADE D C L,JERJEN R,et al.Female pattern hair loss in men:a distinct clinical variant of androgenetic alopecia[J].J Am Acad Dermatol,2021,85(1):260-262.
参考文献 20
LUDWIG E.Classification of the types of androgenetic alopecia(common baldness)occurring in the female sex [J].Br J Dermatol,1977,97(3):247-254.
参考文献 21
KIM M W,SHIN I S,YOON H S,et al.Lipid profile in patients with androgenetic alopecia:a meta-analysis[J].J Eur Acad Dermatol Venereol,2017,31(6):942-951.
参考文献 22
AGAC M T,BEKTAS H,KORKMAZ L,et al.Androgenetic alopecia is associated with increased arterial stiffness in asymptomatic young adults[J].J Eur Acad Dermatol Venereol,2015,29(1):26-30.
参考文献 23
SU L H,CHEN L S,LIN S C,et al.Association of androgenetic alopecia with mortality from diabetes mellitus and heart disease[J].JAMA Dermatol,2013,149(5):601-606.
参考文献 24
ZHANG K,BAI X F,YUAN Z P,et al.Cellular nanofiber structure with secretory activity-promoting characteristics for multicellular spheroid formation and hair follicle regeneration[J].ACS Appl Mater Interfaces,2020,12(7):7931-7941.
参考文献 25
CHEN P,MIAO Y,ZHANG F F,et al.Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine[J].Theranostics,2020,10(25):11673-11689.
参考文献 26
GARZA L A,LIU Y P,YANG Z X,et al.Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia[J].Sci Transl Med,2012,4(126):126ra34.
目录contents

    摘要

    雄激素性秃发 (Androgenetic Alopecia,AGA) 是一种十分常见的毛发疾病,在男性和女性中均可发生。AGA 的主要临床表现为毛发微型化、稀疏、发际线上移,但在男女性中症状有所不同。AGA对个人形象的影响及其治疗效果欠佳的现状,导致患者的日常生活及心理状态都会受到消极影响。本文主要从AGA的发病机制、诊断、治疗、目前面临的挑战及展望等方面对该病进行简述,为探索其诊疗方法提供思路。

    Abstract

    Androgenetic alopecia (AGA) is a very common hair disease, which occurs in both males and females. The clinical manifestations of AGA mainly include miniaturization of hair, thinning of hair and upward movement of hairline, with different symptoms in males and females. The effect of AGA on personal image and its unsatisfactory therapeutic effect lead to negative influence on patients' daily life and psychological state. In this paper, the pathogenesis, diagnosis, treatment, current challenges and the prospects of this disease are briefly described, so as to provide ideas for the exploration of its diagnosis and treatment.

    关键词

    雄激素性秃发机制诊疗

  • 随着社会的进步与经济的发展,大众对于美的追求越来越高,但人们的生活压力显著增加,脱发问题日益严重。雄激素性秃发(Androgenetic Alopecia,AGA) 是一种十分常见的毛发疾病,由于该病会引起毛囊微型化,最终会导致患者头发稀疏、发际线上移,从而对患者的日常生活及心理状态产生消极影响。本文主要从AGA的发病机制、诊断、治疗、目前面临的挑战和对未来的展望等方面对该病进行简述。

  • 1 发病机制

  • AGA的病因是多因素和多基因的。头皮毛囊是雄激素的靶器官之一,全身和局部雄激素代谢异常是AGA发病过程中的重要环节。睾酮和雄烯二酮被5α-还原酶催化转化为二氢睾酮(Dihydrotes⁃ tosterone,DHT),DHT与毛囊细胞上的雄激素受体结合后可使毛囊微小化。男性AGA(Male Androge⁃ netic Alopecia,MAGA) 是雄激素依赖性疾病,虽然遗传方式尚不确定,但观察到明显的遗传易感性,Tosti等人观察了20名青春期前发病的AGA患者,发现他们均具有明显的AGA家族史,而在女性AGA(Female Androgenetic Alopecia, FAGA) 中,雄激素的作用尚不确定,只有1/3的FAGA妇女表现出异常的雄激素水平,在女性秃发患者的一级亲属中发现男性秃发的概率高于对照人群,表明AGA有共同的遗传倾向[1]。此外,头皮慢性炎症、氧化应激、Wnt信号通路的抑制也都参与AGA的发病。

  • 2 诊断与鉴别诊断

  • 2.1 诊断

  • 一般根据典型的临床表现即可诊断AGA,必要时可以结合相关辅助检查确诊并排除其他疾病。 AGA在男性和女性中的表现各具特征,在男性中主要表现为前额发际后移和/或头顶部毛发进行性减少和变细,这种表现形式称为男性型秃发(Male Pattern Alopecia);在女性中主要表现为头顶部毛发进行性减少和变细,呈离心扩张并保留前额发际线不受累,这种表现形式称为女性型秃发(Female Pattern Alopecia)。由于男女的临床表现差异较大,因此,既往对男女性的疾病分级使用不同的评判标准,但是有报道男性可以出现女性型秃发,女性也可以出现男性型秃发,使得有时对于疾病的分级难以定夺,2007年,Lee等人提出了一种男女均适用的新的通用分级法,即BASP(Basic and Specific Classfication) 分型方法,该分型法根据发际线形态、额部与顶部头发密度进行分级[2]

  • 2.2 鉴别诊断

  • 休止期脱发和弥漫性斑秃有时在临床表现上与AGA难以区分,此时需要结合辅助检查来鉴别。

  • 2.2.1 拉发试验(Pull Test)

  • 是指患者5天内不洗发,以拇指和食指拉起一束毛发(大约五六十根),然后用轻力顺着毛干向发梢方向发力,计数拔下的毛发,若超过6根(>10%) 为阳性,表明有活动性脱发。AGA拉发试验阴性,而休止期脱发和弥漫性斑秃为阳性,且后两者有明显的脱发症状。

  • 2.2.2 毛发显微像(Trichogram)

  • 是使用显微镜检查拉发试验中拔出的毛发结构和毛根形态,由此计算生长期和休止期的比例,休止期脱发患者可见到拔出毛发大部分处于休止期。

  • 2.2.3 皮肤镜检查(Dermoscopy)

  • 可以更加清楚地看到毛发形态及直径,毛发粗细不均、毛干直径差异> 20%是AGA的典型皮肤镜表现,而感叹号发是斑秃的典型表现。

  • 2.2.4 其他:

  • 对于女性弥漫性脱发患者而言,由于多囊卵巢综合征、贫血和甲状腺功能异常也可引起脱发,可行性激素、铁蛋白和甲状腺刺激激素(TSH)、卵巢超声等检查加以鉴别。

  • 3 治疗

  • AGA的治疗是一个广受关注的难题,虽然有多种治疗方法,但是目前没有一种疗效明确、反应性好、持久性佳的方法。

  • 3.1 5α还原酶抑制剂

  • 非那雄胺和度他雄胺可以抑制5α 还原酶从而使DHT血清水平降低、抑制毛囊微型化。非那雄胺是美国食品和药物管理局(FDA) 批准的MAGA系统性治疗选择,推荐剂量是每天1mg,该药起效慢,需连续用药3个月及以上才能观察到明显效果;该药需长期使用,因为其中断后AGA病情会继续发展,并在1年内恢复到治疗前状态。非那雄胺在女性中的疗效尚不明确[3],且服用非那雄胺会导致男性胎儿的女性化,也会使女性体内雌激素水平升高,在理论上增加乳腺癌的风险,因此,非那雄胺目前未被FDA批准用于女性,并在有生育要求的妇女中禁用。度他雄胺每天0.5mg已被批准用于全球范围内的良性前列腺增生治疗,但仅在韩国和墨西哥等少数几个国家/地区批准用于AGA治疗。 2014年,Gupta等人的荟萃分析表明,非那雄胺和度他雄胺对AGA治疗同样有效[4]。非那雄胺对男性性功能的影响也一直是人们关注的问题,一般认为其发生率低且症状轻微,Haber等人的研究表明非那雄胺的使用不会导致AGA男性的性功能障碍[5]。鉴于系统使用5α 还原酶可能带来不良反应,2009年一项小型随机对照试验比较了局部和口服非那雄胺对45例MAGA患者的治疗效果,结果发现外用非那雄胺凝胶和口服片剂的治疗效果相似,在两个治疗组中均未观察到性功能副作用[6]

  • 3.2 雄激素受体及雄激素拮抗剂

  • 雄激素受体拮抗剂未经FDA批准,但经常用于治疗FAGA(超处方用药)。螺内酯是保钾利尿剂,因为能阻断靶组织中的雄激素受体从而被认为可以抗雄激素,每天50~200mg的剂量用于治疗FAGA有良好的安全性[7-9],但其使用疗程至少需1年,且有月经紊乱、性欲降低、乳房胀痛和高血钾的风险,故应用仍需谨慎。醋酸环丙孕酮是雄激素的竞争性拮抗剂,可以减少循环中游离雄激素的含量,在FAGA治疗中与螺内酯之间没有差异[10],但该药物的不良反应包括肝毒性、体重增加、性欲下降、乳房压痛和男性胎儿的女性化。此外,德国和美国正在进行外用雄激素受体抑制剂克拉斯科酮治疗AGA的临床研究。

  • 3.3 雄激素非依赖性疗法

  • 米诺地尔是第一个也是唯一被FDA批准用于治疗AGA的局部用药,在男性中目前批准使用2%、5%的溶液剂型和5%的泡沫剂型,在女性中则是批准了2%的溶液剂型和5%的泡沫剂型。米诺地尔对毛发生长的作用机理尚不清楚,可能是通过钾通道开放介导,导致皮肤血流量增加、真皮乳头中的血管内皮生长因子和毛发生长促进剂水平升高,从而使毛发生长[11]。在MAGA中,5%米诺地尔溶液的推荐剂量为1mL、每天两次,而5%米诺地尔泡沫剂的剂量为半盖(0.5mL)、每天两次。对于女性,建议剂量为2%溶液1mL、每天两次,或5%泡沫剂半盖(0.5mL)、每天一次。该药应需至少使用6个月后再评估疗效,并应长时间使用以保持疗效,药物中断3-4个月后可能引起急性脱发,而且不建议孕妇使用米诺地尔。

  • 3.4 手术治疗

  • 对于25岁以上、病情稳定的患者,植发是一种可行的治疗选择,其原理在于雄激素不敏感区域的毛囊即使移植到雄激素敏感区域的头皮也能保持其特性,移植后的毛囊一般可以保持长久的存活。近年来随着毛发移植技术的不断改进,毛囊单位抽取移植技术日趋成熟和标准化,应用逐渐广泛。但是由于其经济成本较高、个体差异大、供区资源不足等原因,对于中低收入家庭以及枕后毛发稀疏的患者仍然难以实行。

  • 3.5 其他新兴疗法

  • 3.5.1 激光治疗

  • 低能量激光疗法(Low-level La⁃ ser Therapy,LLLT) 是一种新发展起来的技术,已被证明能刺激头发生长,但目前针对LLLT的研究还不够充分,需要更多的研究来标准化用于促进头发生长的最佳治疗参数,并确定LLLT的长期安全性和有效性。

  • 3.5.2 微针治疗

  • 微针技术是一种微创技术,可以诱导胶原蛋白的形成、生长因子的产生和新生血管的形成,有研究证明其可能增加头发的密度、厚度和头发质量,特别是当与其他疗法结合使用或用作药物输送系统时。但是目前还没有针对微针治疗脱发的标准化方案。

  • 3.5.3 富含血小板血浆治疗

  • 血小板含有刺激干细胞的生长因子和细胞因子,在FAGA患者中进行的一项前瞻性随机对照试验显示,实验组较安慰剂组有明显改善,但也有研究报道二者无明显差异[12, 13],因此尚需要更多研究证明该治疗方法的有效性及安全性。

  • 3.5.4 肉毒素

  • 皮内注射肉毒素可通过抑制毛发中TGF-β1的分泌来有效对抗AGA,Shon等人的研究表明使用肉毒素24周后秃发情况有明显改善,但是注射部位及剂量的选择需要进一步的研究和长期的随访[14]

  • 3.5.5 脂肪干细胞成分提取物

  • 脂肪干细胞是一种间充质干细胞,它能分泌多种生长激素来帮助细胞发育和增殖,Tak等人的研究表明使用脂肪干细胞成分提取物的毛发数量比对照组增加更多[15]

  • 3.5.6 新型局部增强剂

  • 米诺地尔局部治疗时大约60%~70%的患者没有明显的头发增长效果[16],米诺地尔是一种前药,需要通过磺基转移酶转化为硫酸米诺地尔才能发挥生物作用,Ramos等人发现使用局部增强剂(一种脂质体封装的碱化剂) 能够增加毛囊中磺基转移酶的活性,这可能会提高局部和小剂量口服米诺地尔治疗AGA的疗效[17],但仍需大量研究验证其临床疗效。

  • 3.5.7 牛胎盘提取物

  • 在一项双盲、随机对照试验中,比较了2%米诺地尔溶液和牛胎盘溶液治疗FAGA的疗效,发现到第六个月末,两组总毛发数量均增加,说明外用牛胎盘素溶液的有效性可达到2%米诺地尔的效果[18]

  • 4 诊疗挑战

  • 4.1 诊断挑战

  • 通常情况下,AGA具有其典型模式,但是也有男性出现女性型秃发,在这类患者中,部分观察到低睾丸激素血症和维生素D缺乏症,需要进一步的研究来确认睾丸激素和维生素D在男性的女性型秃发患者发病机理中的作用[19]。并且,在女性中也有表现为中央头皮受累、前额发际处头发减少的路德维希模式[20]。另外,AGA还需与弥漫性斑秃和休止期脱发相鉴别。AGA发病缓慢,无明显诱因,拉发试验阴性。弥漫性斑秃发病较快,拉发试验阳性,且可出现“感叹号”样发。休止期脱发常有诱因,追问病史可寻其线索,拉发试验阳性,特别需要注意的是,由于当代年轻人多有精神压力大、睡眠质量差、作息不规律等情况,AGA患者经常同时合并有休止期脱发,值得引起重视。

  • 另外,既往研究证明雄激素与血脂异常、动脉硬化等多种系统性疾病的发生相关,而且AGA是男性和女性糖尿病及心脏病死亡率的独立预测因子[21-23],因此,在诊断AGA时应考虑这些系统疾病共存的可能性。

  • 4.2 治疗挑战

  • 在国内外AGA的研究热度很高,但是人们对于AGA的发病机制的认识依然很欠缺,传统的药物治疗效果不佳,因此,尚需要对AGA的发病机制进行研究以找到新的、更有效的治疗靶点。由于AGA是一个进行性加重的过程,因此应强调早期治疗和长期治疗的重要性。一般而言,治疗越早疗效越好。早期、轻症的AGA患者相较于晚期、重症患者治疗效果好,但人们于皮肤科就诊时多已处于较严重的程度,加上患者对长期用药的依从性不足以及无法承受手术治疗的高昂价格,因此,虽然多种新兴治疗方法都在积极探索,但目前AGA的治疗仍是一项挑战。

  • 5 展望

  • 目前AGA的治疗还是一项艰巨的挑战,但是多种新兴治疗方法的尝试也为人们带来了希望。毛乳头(Dermal Papilla,DP) 由间充质细胞组成,这些细胞在诱导毛囊干细胞活化及毛囊再生方面起着重要作用,但体外培养会很快失去这种诱导能力,科学家已在尝试多种方法来维持DP细胞的这种能力,Zhang等人的研究结果显示,纳米纤维海绵可以提高DP细胞的分泌活性,并恢复它们的固有特性,有效地增强DP细胞诱导毛囊再生的能力[24];另外,人工构建的纳米级仿生细胞外基质可以使自体毛囊干细胞稳定扩增并保持其干细胞特性[25],这为毛发移植的毛囊来源带来了新方向。此外,人们对于AGA发病的新靶点也在不断探究[26],这为开发AGA治疗药物提供了新的思路。

  • 参考文献

    • [1] TOSTI A,IORIZZO M,PIRACCINI B M.Androgenetic alopecia in children:report of 20 cases[J].Br J Dermatol,2005,152(3):556-559.

    • [2] LEE W S,RO B I,HONG S P,et al.A new classification of pattern hair loss that is universal for men and women:basic and specific(BASP)classification[J].J Am Acad Dermatol,2007,57(1):37-46.

    • [3] KANTI V,MESSENGER A,DOBOS G,et al.Evidencebased(S3)guideline for the treatment of androgenetic alopecia in women and in men-short version[J].J Eur Acad Dermatol Venereol,2018,32(1):11-22.

    • [4] GUPTA A K,CHARRETTE A.The efficacy and safety of 5 alpha-reductase inhibitors in androgenetic alopecia:a network meta-analysis and benefit-risk assessment of finasteride and dutasteride[J].J Dermatolog Treat,2014,25(2):156-161.

    • [5] HABER R S,GUPTA A K,EPSTEIN E,et al.Finasteride for androgenetic alopecia is not associated with sexual dysfunction:a survey-based,single-centre,controlled study[J].J Eur Acad Dermatol Venereol,2019,33(7):1393-1397.

    • [6] HAJHEYDARI Z,AKBARI J,SAEEDI M,et al.Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia[J].Indian J Dermatol Venereol Leprol,2009,75(1):47-51.

    • [7] BURKE B M,CUNLIFFE W J.Oral spironolactone therapy for female patients with acne,hirsutism or androgenic alopecia[J].Br J Dermatol,1985,112(1):124-125.

    • [8] CAMACHO-MARTINEZ F M.Hair loss in women[J].Semin Cutan Med Surg,2009,28(1):19-32.

    • [9] RATHNAYAKE D,SINCLAIR R.Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss[J].Dermatol Clin,2010,28(3):611-618.

    • [10] SINCLAIR R,WEWERINKE M,JOLLEY D.Treatment of female pattern hair loss with oral antiandrogens[J].Br J Dermatol,2005,152(3):466-473.

    • [11] ROSSI A,CANTISANI C,MELIS L,et al.Minoxidil use in dermatology,side effects and recent patents[J].Recent Pat Inflamm Allergy Drug Discov,2012,6(2):130-136.

    • [12] SHAPIRO J,HO A,SUKHDEO K,et al.Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1298-1303.

    • [13] DUBIN D P,LIN M J,LEIGHT H M,et al.The effect of platelet-rich plasma on female androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1294-1297.

    • [14] SHON U,KIM M H,LEE D Y,et al.The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism[J].J Am Acad Dermatol,2020,83(6):1838-1839.

    • [15] TAK Y J,LEE S Y,CHO A R,et al.A randomized,double-blind,vehicle-controlled clinical study of hair regeneration using adipose-derived stem cell constituent extract in androgenetic alopecia[J].Stem Cells Transl Med,2020,9(8):839-849.

    • [16] ADIL A,GODWIN M.The effectiveness of treatments for androgenetic alopecia:a systematic review and metaanalysis[J].J Am Acad Dermatol,2017,77(1):136-141.

    • [17] RAMOS P M,MCCOY J,WAMBIER C,et al.Novel topical booster enhances follicular sulfotransferase activity in patients with androgenetic alopecia:a new strategy to improve minoxidil response[J].J Eur Acad Dermatol Venereol,2020,34(12):e799-e800.

    • [18] BARAT T,ABDOLLAHIMAJD F,DADKHAHFAR S,et al.Evaluation of the efficacy and safety of cow placenta extract lotion versus minoxidil 2% in the treatment of female pattern androgenetic alopecia[J].Int J Womens Dermatol,2020,6(4):318-321.

    • [19] KERKEMEYER K L,TRINDADE D C L,JERJEN R,et al.Female pattern hair loss in men:a distinct clinical variant of androgenetic alopecia[J].J Am Acad Dermatol,2021,85(1):260-262.

    • [20] LUDWIG E.Classification of the types of androgenetic alopecia(common baldness)occurring in the female sex [J].Br J Dermatol,1977,97(3):247-254.

    • [21] KIM M W,SHIN I S,YOON H S,et al.Lipid profile in patients with androgenetic alopecia:a meta-analysis[J].J Eur Acad Dermatol Venereol,2017,31(6):942-951.

    • [22] AGAC M T,BEKTAS H,KORKMAZ L,et al.Androgenetic alopecia is associated with increased arterial stiffness in asymptomatic young adults[J].J Eur Acad Dermatol Venereol,2015,29(1):26-30.

    • [23] SU L H,CHEN L S,LIN S C,et al.Association of androgenetic alopecia with mortality from diabetes mellitus and heart disease[J].JAMA Dermatol,2013,149(5):601-606.

    • [24] ZHANG K,BAI X F,YUAN Z P,et al.Cellular nanofiber structure with secretory activity-promoting characteristics for multicellular spheroid formation and hair follicle regeneration[J].ACS Appl Mater Interfaces,2020,12(7):7931-7941.

    • [25] CHEN P,MIAO Y,ZHANG F F,et al.Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine[J].Theranostics,2020,10(25):11673-11689.

    • [26] GARZA L A,LIU Y P,YANG Z X,et al.Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia[J].Sci Transl Med,2012,4(126):126ra34.

  • 参考文献

    • [1] TOSTI A,IORIZZO M,PIRACCINI B M.Androgenetic alopecia in children:report of 20 cases[J].Br J Dermatol,2005,152(3):556-559.

    • [2] LEE W S,RO B I,HONG S P,et al.A new classification of pattern hair loss that is universal for men and women:basic and specific(BASP)classification[J].J Am Acad Dermatol,2007,57(1):37-46.

    • [3] KANTI V,MESSENGER A,DOBOS G,et al.Evidencebased(S3)guideline for the treatment of androgenetic alopecia in women and in men-short version[J].J Eur Acad Dermatol Venereol,2018,32(1):11-22.

    • [4] GUPTA A K,CHARRETTE A.The efficacy and safety of 5 alpha-reductase inhibitors in androgenetic alopecia:a network meta-analysis and benefit-risk assessment of finasteride and dutasteride[J].J Dermatolog Treat,2014,25(2):156-161.

    • [5] HABER R S,GUPTA A K,EPSTEIN E,et al.Finasteride for androgenetic alopecia is not associated with sexual dysfunction:a survey-based,single-centre,controlled study[J].J Eur Acad Dermatol Venereol,2019,33(7):1393-1397.

    • [6] HAJHEYDARI Z,AKBARI J,SAEEDI M,et al.Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia[J].Indian J Dermatol Venereol Leprol,2009,75(1):47-51.

    • [7] BURKE B M,CUNLIFFE W J.Oral spironolactone therapy for female patients with acne,hirsutism or androgenic alopecia[J].Br J Dermatol,1985,112(1):124-125.

    • [8] CAMACHO-MARTINEZ F M.Hair loss in women[J].Semin Cutan Med Surg,2009,28(1):19-32.

    • [9] RATHNAYAKE D,SINCLAIR R.Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss[J].Dermatol Clin,2010,28(3):611-618.

    • [10] SINCLAIR R,WEWERINKE M,JOLLEY D.Treatment of female pattern hair loss with oral antiandrogens[J].Br J Dermatol,2005,152(3):466-473.

    • [11] ROSSI A,CANTISANI C,MELIS L,et al.Minoxidil use in dermatology,side effects and recent patents[J].Recent Pat Inflamm Allergy Drug Discov,2012,6(2):130-136.

    • [12] SHAPIRO J,HO A,SUKHDEO K,et al.Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1298-1303.

    • [13] DUBIN D P,LIN M J,LEIGHT H M,et al.The effect of platelet-rich plasma on female androgenetic alopecia:a randomized controlled trial[J].J Am Acad Dermatol,2020,83(5):1294-1297.

    • [14] SHON U,KIM M H,LEE D Y,et al.The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism[J].J Am Acad Dermatol,2020,83(6):1838-1839.

    • [15] TAK Y J,LEE S Y,CHO A R,et al.A randomized,double-blind,vehicle-controlled clinical study of hair regeneration using adipose-derived stem cell constituent extract in androgenetic alopecia[J].Stem Cells Transl Med,2020,9(8):839-849.

    • [16] ADIL A,GODWIN M.The effectiveness of treatments for androgenetic alopecia:a systematic review and metaanalysis[J].J Am Acad Dermatol,2017,77(1):136-141.

    • [17] RAMOS P M,MCCOY J,WAMBIER C,et al.Novel topical booster enhances follicular sulfotransferase activity in patients with androgenetic alopecia:a new strategy to improve minoxidil response[J].J Eur Acad Dermatol Venereol,2020,34(12):e799-e800.

    • [18] BARAT T,ABDOLLAHIMAJD F,DADKHAHFAR S,et al.Evaluation of the efficacy and safety of cow placenta extract lotion versus minoxidil 2% in the treatment of female pattern androgenetic alopecia[J].Int J Womens Dermatol,2020,6(4):318-321.

    • [19] KERKEMEYER K L,TRINDADE D C L,JERJEN R,et al.Female pattern hair loss in men:a distinct clinical variant of androgenetic alopecia[J].J Am Acad Dermatol,2021,85(1):260-262.

    • [20] LUDWIG E.Classification of the types of androgenetic alopecia(common baldness)occurring in the female sex [J].Br J Dermatol,1977,97(3):247-254.

    • [21] KIM M W,SHIN I S,YOON H S,et al.Lipid profile in patients with androgenetic alopecia:a meta-analysis[J].J Eur Acad Dermatol Venereol,2017,31(6):942-951.

    • [22] AGAC M T,BEKTAS H,KORKMAZ L,et al.Androgenetic alopecia is associated with increased arterial stiffness in asymptomatic young adults[J].J Eur Acad Dermatol Venereol,2015,29(1):26-30.

    • [23] SU L H,CHEN L S,LIN S C,et al.Association of androgenetic alopecia with mortality from diabetes mellitus and heart disease[J].JAMA Dermatol,2013,149(5):601-606.

    • [24] ZHANG K,BAI X F,YUAN Z P,et al.Cellular nanofiber structure with secretory activity-promoting characteristics for multicellular spheroid formation and hair follicle regeneration[J].ACS Appl Mater Interfaces,2020,12(7):7931-7941.

    • [25] CHEN P,MIAO Y,ZHANG F F,et al.Nanoscale microenvironment engineering based on layer-by-layer self-assembly to regulate hair follicle stem cell fate for regenerative medicine[J].Theranostics,2020,10(25):11673-11689.

    • [26] GARZA L A,LIU Y P,YANG Z X,et al.Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia[J].Sci Transl Med,2012,4(126):126ra34.

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