Transcript The Evidence: （研究重要結果）

皮膚 科
實證期刊閱讀報告
EBM-style Journal Reading
報告人： 陳清筠 Email: [email protected]
指導臨床教師：蔡妍筠
日期：102-4-25
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。
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Clinical Uncertainty → PICO 問題
Dopamine對毛囊生長是否有影響?
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臨床個案的PICO
Patient / Problem
Hirsutism, female
Intervention
bromocriptine
Comparison
control
Outcome
hair shaft elongation, hair
cycle stage and score
Type of Question:
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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"
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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
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Level
1a
1b
1c
2a
2b
2c
3a
3b
4
5
Therapy / Prevention, Aetiology / Harm
SR (with homogeneity) of RCTs
Individual RCT (with narrow Confidence Interval)
All or none
SR (with homogeneity) of cohort studies
Individual cohort study (including low quality RCT; e.g., <80%
follow-up)
"Outcomes" Research; Ecological studies
SR (with homogeneity*) of case-control studies
Individual Case-Control Study
Case-series (and poor quality cohort and case-control studies)
Expert opinion without explicit critical appraisal, or based on
physiology, bench research or "first principles"
降階原因 : 個別的RCT異質性高，且結果不顯著
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Grades of Recommendation
A
consistent level 1 studies
B
consistent level 2 or 3 studies or
extrapolations from level 1 studies
C
level 4 studies or extrapolations from level 2 or
3 studies
D
level 5 evidence or troublingly inconsistent or
inconclusive studies of any level
"Extrapolations" are where data is used in a situation that has potentially clinically
important differences than the original study situation.
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The Study: （研究效度）- 1
Level
1a
1b
1c
2a
2b
2c
3a
3b
4
5
Therapy / Prevention, Aetiology / Harm
SR (with homogeneity) of RCTs
Individual RCT (with narrow Confidence Interval)
All or none
SR (with homogeneity) of cohort studies
Individual cohort study (including low quality RCT; e.g., <80%
follow-up)
"Outcomes" Research; Ecological studies
SR (with homogeneity*) of case-control studies
Individual Case-Control Study
Case-series (and poor quality cohort and case-control studies)
Expert opinion without explicit critical appraisal, or based on
physiology, bench research or "first principles"
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Grades of Recommendation
A
consistent level 1 studies
B
consistent level 2 or 3 studies or
extrapolations from level 1 studies
C
level 4 studies or extrapolations from level 2 or
3 studies
D
level 5 evidence or troublingly inconsistent or
inconclusive studies of any level
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The Study: （研究效度）- 2
 Level of Evidence: Level 1b, Grade B
(randomized study design, extrapolations)
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The Study: （研究效度）- 3
本篇文獻的PICO (T)
Patient /
Problem
Microdissected anagen VI HFs were obtained from
redundant scalp skin, as a by-product of cosmetic
surgery, with ethical approval and written informed
consent.
Intervention
Microdissected HFs were cultured in a supplemented,
serum-free culture medium for 7 days with the addition of
dopamine, 10–1000 nmol L-1 or culture medium only.
Comparison
Microdissected HFs were cultured in a supplemented,
serum-free culture medium for 7 days, with culture
medium only.
Outcome
Hair shaft elongation was measured as the percentage
elongation from baseline, and hair cycle stage and hair
cycle score were determined morphometrically.
Time
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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).
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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
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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
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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 catagenpromoting 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
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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.
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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 DRmediated 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.
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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.
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回到臨床個案情境
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
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References:
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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 cultured cultured 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
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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 sitespecific effects on the human hair follicle? J Invest Dermatol 2010; 130:886–91.
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結 論 （標題 Title）
 Dopamine is a novel, direct inducer of
catagen in human scalp hair follicles in
vitro.
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