皮膚 科 實 證 期 刊 閱 讀 報 告 EBM-style Journal Reading

1. 皮膚科實 證 期 刊 閱 讀 報 告EBM-style Journal Reading 報告人： 陳清筠 Email:137989@cch.org.tw 指導臨床教師：蔡妍筠 日期：102-4-25

2. Clinical Scenario （臨床情境） • 一位43歲女性病患因罹患多毛症(hirsutism)多年至皮膚科門診求診，曾在報章報導看過多巴胺可有效治療多毛症，想進一步了解相關資訊。

3. Clinical Uncertainty → PICO 問題 • Dopamine對毛囊生長是否有影響?

4. 臨床個案的PICO Type of Question:

5. Search Terms & Strategy:（搜尋關鍵字與策略） • 資料庫： Pubmed • 搜尋日期： 102-4-10 • 搜尋關鍵字與隅策略： • “ Hirsutism” AND “dopamine OR bromocriptine"

6. Best available evidence:（挑選可獲得之最佳研究證據） • Citation/s: Dopamine is a novel, direct inducer of catagen in human scalp hair follicles in vitro • Lead author's name : E.A. Langan

7. 降階原因 : 個別的RCT異質性高，且結果不顯著

8. Grades of Recommendation "Extrapolations" are where data is used in a situation that has potentially clinically important differences than the original study situation.

9. The Study: （研究效度）- 1

10. Grades of Recommendation

11. The Study: （研究效度）- 2 • Level of Evidence: Level 1b, Grade B (randomized study design, extrapolations)

12. The Study: （研究效度）- 3本篇文獻的PICO (T)

13. The Evidence: （研究重要結果）- 1 • Dopamine 1000 nmol L)1 increased the percentage of HFs in the catagen phase of the hair cycle, which was also mirrored by a significant increase in the hair cycle score (P = 0.01).

14. The Evidence: （研究重要結果）- 2 • Tyrosinase activity in situ and Gp100 IR were not significantly affected by dopamine 1000 nmol L-1

15. The Evidence: （研究重要結果）- 3 • When pigmentary parameters were compared only between test and control HFs that were all in anagen VI, there was no hair cycle-independent effect of dopamine on intrafollicular pigmentation

16. The Evidence: （研究重要結果）- 4 • The percentage of Ki67-positive cells in the hair matrix below Auber’s line, the widest part of the dermal papilla, was assessed in anagen VI HFs. • Dopamine 10 and 100 nmol L-1 significantly reduced the percentage of Ki67-positive cells when compared with the control group, in line with the catagen-promoting effects of dopamine noted above. Although there was a decreased percentage of Ki67-positive matrix keratinocytes at 1000 nmol L-1 dopamine, this was not statistically significant. • There was no significant increase in the percentage of apoptotic (TUNEL-positive) cells at 10 nmol L-1 or 100 nmol L-1. However, there was a trend towards increasedTUNEL positivity in HFs treated with dopamine1000 nmol L-1

17. The Evidence: （研究重要結果）-5 • Dopamine had no consistent effect on shaft elongation in the HF, at the concentrations tested. However, there was a (nonsignificant) trend towards decreased shaft elongation in the 10 and 100 nmol L-1 treatment groups.

18. Comment & Discussion: -1 • This study provides the first evidence that dopamine treatment negatively affects human hair growth, namely that it promotes HF regression (catagen) in female anagen VI HFs in organ culture. This is entirely consistent with the in vivo case reports of hair loss in patients being treated with dopamine agonists. • While the precise mechanism(s) by which dopamine induces premature catagen development in female human anagen HFs remains to be elucidated, the intrafollicular presence of DR transcripts suggests a DR-mediated mechanism. • It remains unclear whether the observed intra-follicular effects of dopamine on the HF operate, via DR, or indirectly, via the modulation of other locally generated hormones, for example, PRL.

19. Comment & Discussion: -2 • Clinically, these data shed new light on the neuroendocrinology of human hair growth and provide encouraging preclinical evidence that dopamine and DR agonists may be useful as novel antihirsutism agents. • Conversely these raise the possibility that DR antagonists may exert novel hair growth-promoting effects.

20. Clinical bottom line 臨床決策底線 多巴胺對毛囊的生長的確有抑制作用，但目前仍在實驗階段，臨床實際應用仍須更多證據。 證據等級1b, 建議等級B 回到臨床個案情境

21. References: 1. Grauer MT, Sieb JP. Alopecia induced by dopamine agonists. Neurology 2002; 59:2012. 2 Marshall A, Williams MJ. Alopecia and levodopa. Br Med J 1971; 2:47. 3 Katz KA, Cotsarelis G, Gupta R, Seykora JT. Telogen effluvium associated with the dopamine agonist pramipexole in a 55-year-old woman with Parkinson’s disease. J Am Acad Dermatol 2006; 55:S103–4. 4 Miwa H, Kondo T. Hair loss induced by dopamine agonist: casereport and review of the literature. Parkinsonism Relat Disord 2003; 10:51–2. 5 Borcherding DC, Hugo ER, Idelman G et al. Dopamine receptors in human adipocytes: expression and functions. PLoS ONE 2011; 6:e25537. 6 Rubi B, Maechler P. Minireview: new roles for peripheral dopamineon metabolic control and tumor growth: let’s seek the balance. Endocrinology 2010; 151:5570–81. 7 Laengle UW, Markstein R, Pralet D et al. Effects of latanoprost and GLC756, a novel dopamine D2 agonist and D1 antagonist, on culturedcultured normal human dermal fibroblasts. Eur J Ophthalmol 2006; 16:67–72. 8 Shome S, Rana T, Ganguly S et al. Dopamine regulates angiogenesis in normal dermal wound tissues. PLoS ONE 2011; 6:e25215. 9 Ramchand CN, Clark AE, Ramchand R, Hemmings GP. Cultured human keratinocytes as a model for studying the dopamine metabolism in schizophrenia. Med Hypotheses 1995; 44:53–7. 10 Chang YT, Hyland K, Mues G, Marsh JL. Human hair follicles as aperipheral source of tyrosine hydroxylase and aromatic L-amino acid decarboxylase mRNA. Neurosci Lett 1997; 222:210–12. 11. Lu Z, Hasse S, Bodo E et al. Towards the development of a simplified long-term organ culture method for human scalp skin and its appendages under serum-free conditions. Exp Dermatol 2007; 16:37–44. 12 Kloepper JE, Sugawara K, Al-Nuaimi Y et al. Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Exp Dermatol 2010; 19:305–12. 13 Ramot Y, Bı´ro´ T, Tiede S et al. Prolactin – a novel neuroendocrine regulator of human keratin expression in situ. Faseb J 2010; 24:1768–79

22. References: 14. Gaspar E, Nguyen-Thi KT, Hardenbicker C et al. Thyrotropin-releasing hormone selectively stimulates human hair follicle pigmentation. J Invest Dermatol 2011; 131:2368–77. 15 Samuelov L, Sprecher E, Tsuruta D et al. P-Cadherin regulates human hair growth and cycling via canonical Wnt signaling and transforming growth factor-beta2. J Invest Dermatol 2012; 132:2332–41. 16 Gautam M. Alopecia due to psychotropic medications. Ann Pharmacother 1999; 33:631–7. 17 Tabamo RE, Di Rocco A. Alopecia induced by dopamine agonists. Neurology 2002; 58:829–30. 18 Samuelov L, Kinori M, Bertolini M, Paus R. Neural controls of human hair growth: calcitonin gene-related peptide (CGRP) induces catagen. J Dermatol Sci 2012; 67:153–5. 19 Fuziwara S, Suzuki A, Inoue K, Denda M. Dopamine D2-like receptor agonists accelerate barrier repair and inhibit the epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 2005; 125:783–9. 20 Langan EA, Ramot Y, Goffin V et al. Mind the (gender) gap: does prolactin exert gender- and ⁄or site-specific effects on the human hair follicle? J Invest Dermatol 2010; 130:886–91.

23. 結 論 （標題 Title） • Dopamine is a novel, direct inducer of catagen in human scalp hair follicles in vitro.

24. 敬請指教