Vitamin E merupakan anti oksidan alami yang membantu seluruh

sel dan jaringan tubuh memperbaiki dan mengatasi peradangan.

Nyeri haid berhubungan dengan keluhan peradangan atau
inflamasi.
Asupan vitamin E membantu menstabilkan aliran menstruasi
dengan memperbaiki lapisan rahim. Studi yang dipublikasikan
tahun 2005 dalam ritish !ournal of "bstetri#s and $ynae#ology
menunjukkan bah%a vitamin E dapat mengurangi keparahan dan
durasi periode sakit serta kehilangan darah menstruasi yang #ukup
banyak.
&osis yang diberikan adalah 200 '( vitamin E kapsul 2 kali sehari)
dua hari sebelum dan tiga hari setelah menstruasi dimulai.
Sebaiknya konsumsi vitamin E alami) dikenal sebagai tokoferol
gabungan yang mendekati komposisi tokoferol alami yang
dijumpai pada makanan. Se#ara alami vitamin E bisa diperoleh
dari ka#ang almond) biji bunga matahari) dan gandum.
Vitamin lain yang juga bisa digunakan adalah vitamin *.
Vitamin * atau tiamin dengan dosis *00mg perhari dapat
mengurangi rasa nyeri. Vitamin ada dalam gandum) gist) susu
kedelai) dan biji bunga matahari.
Abstract

E+perimental eviden#e is a##umulating to suggest that medi#inal

botani#als have anti,
inflammatory and pain,alleviating properties

and hold promise for treatment of
endometriosis. -erein) %e

present a systemati# revie% of
#lini#al and e+perimental data

on the use of medi#inal
herbs in the treatment of endometriosis.

Although there is
a general la#k of eviden#e from #lini#al studies

on the
potential effi#a#y of medi#inal herbs for the treatment

of
endometriosis,asso#iated symptoms) our revie%
highlights

the anti,inflammatory and pain,alleviating
me#hanisms of a#tion

of herbal remedies. .edi#inal
herbs and their a#tive #omponents

e+hibit #ytokine,
suppressive) /"0,2,inhibiting) antio+idant)

sedative and
pain,alleviating properties. Ea#h of these me#hanisms

of
a#tion %ould be predi#ted to have salutary effe#ts in
endometriosis.

etter understanding of the me#hanisms
of a#tion) to+i#ity and

herb1herb and herb1drug intera#tions permits the

optimi2ation of
design and e+e#ution of #omplementary alternative

medi#ine trials for endometriosis,
asso#iated pain. A potential

benefit of herbal therapy is the likelihood of synergisti#
intera#tions

%ithin individual or #ombinations of plants. 'n this sense)

phytotherapies may
be analogous to nutra#euti#als or %hole food

nutrition. 3e en#ourage the development of
herbal analogues

and establishment of spe#ial) simplified registration pro#edures

for
#ertain medi#inal produ#ts) parti#ularly herbal derivates

%ith a long tradition of safe use.

Key words: endometriosis 4 herbs 4 botani#als 4 inflammation 4 /A.
Introduction
TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s

5he su##essful treatment of endometriosis,asso#iated
symptoms

in#luding d$smenorrhoea) dyspareunia and
#hroni# non,menstrual

pain typi#ally re6uires surgi#al as
%ell medi#al intervention

78ennedy et al.) 2005 9. 5he
use of both general modalities for

endometriosis,
asso#iated pain has been re#ently revie%ed 78ennedy

et
al.) 2005 : /rosignani et al.) 200; 9. 5he #lini#al
prevalen#e

of endometriosis symptomatology is very
high. 'n a survey of

reprodu#tive,aged %omen in /anada)
;0< met the #riteria for

primary dysmenorrhea 7urnett
et al.) 2005 9. 'n adult %omen

%ith endometriosis) the
prevalen#e rate of d$smenorrhoea %as

up to =;<
78uohung et al.) 2002 9) and in adoles#ents %ith endometriosis)

it %as up to >?< 7@eese
et al.) *>>; 9. 5his disease #onstitutes

a publi# health dilemma of major proportion.
Although medi#al

therapies are not #urative per se) they are nonetheless a mainstay

of
pain symptom suppression among %omen %ith endometriosis.

'nitially high,dose diethylstilbestrol and #ombinations of potent

estrogens and
progestagens %ere used to treat endometriosis

7-ur+thal and Smith) *>52 9) but this
approa#h %as subse6uently

repla#ed by progestagens alone 78istner) *>5A 9. 'n *>5A) the

#lini#al observation of an apparent resolution of symptoms during

pregnan#y gave rise to
the #on#ept of treating patients %ith

pseudo,pregnan#y hormone regimens 78istner) *>5A
9. &ifferent

forms of progestagens and anti,progestagens 7in#luding dihydrogesterone)

medro+yprogesterone a#etate 7.BA9) gestrinone and mifepristone

7@( ?A;9 afforded
some improvement in pelvi# pain: ho%ever)

these treatments are ineffe#tive in a subset of
%omen %ith endometriosis

and #arry several unto%ard side effe#ts 7Ver#ellini et al.)

*>>= 9. 'n *>=C) dana2ol) a iso+a2ole derivative of *=,alpha

testosterone) %as introdu#ed
for the treatment of endometriosis,asso#iated

pain 7Driedlander) *>=C 9. Although
dana2ol is effe#tive) e+tended

use is limited by androgeni# and metaboli# side effe#ts
7Selak

et al.) 200* 9. A de#ade later) in *>A2) gonadotrophin releasing

hormone agonists
7$n@-,a9 %ere first des#ribed as an alternative

treatment for endometriosis 7Eemay and
Fuesnel) *>A2 9. Although

$n@-,a #an be used safely %ith #ombined estrogen and4or
progestagen

add,ba#k therapy for up to 2 years) long,term use is #onstrained

by
hypoestrogeni# side effe#ts 7/orson and olognese) *>=A 9)

espe#ially in adoles#ents.

Sin#e *>=A) non,hormonal treatment regimens for endometriosis,asso#iated

pain)
in#luding a variety of non,steroidal anti,inflammatory

drugs 7NSA'&s9) have been
promoted 7/orson and olognese) *>=A 9.

"bje#tive eviden#e on the use of NSA'&s in
endometriosis,asso#iated

pain is sparse and in#on#lusive 7Allen et al.) 2005 9. &espite

the poor 6uality of eviden#e) NSA'&s are typi#ally used as first,line

drugs in the
treatment of endometriosis asso#iated,pain) be#ause

they are felt to have fe%er limitations
7Allen et al.) 2005 9.

.u#h effort is spent on the development and promotion of ne%

drug treatments %ith the
goal of a#hieving higher effi#a#y)

fe%er side effe#ts and the option of long,term
treatment) espe#ially

in %omen %ith severe endometriosis. 5hese agents in#lude
TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
thia2olidinediones

7Eebovi# et al.) 200? 9) sele#tive progesterone re#eptor modulators

7SB@.s9 7/h%alis2 et al.) 2005 9) aromatase inhibitors 7Amsterdam

et al.) 2005 9)
#y#loo+ygenase 7/"09,2 sele#tive NSA'&s 7/obellis

et al.) 200? 9) re#ombinant human
5ND,alpha binding proteins

7arrier et al.) 200? 9) anti,VE$D therapy 7Nap et al.) 2005
9)

..B,inhibitors 7.ori et al.) 200* 9 and interferon,alpha,2b 7ada%y

et al.) 200* 9.
Eviden#e from pre,#lini#al trials has suggested

benefi#ial effe#ts of these drugs that may
be #onferred by anti,proliferative)

anti,inflammatory or anti,angiogeni# me#hanisms.
-o%ever) despite

these many therapeuti# options) effi#ient long,term regimens

for the
treatment of endometriosis,asso#iated symptoms are desperately

needed.

'n re#ent years) medi#inal herbs and other botani#al produ#ts

have be#ome popular for
management of symptoms of several gynae#ologi#

disorders 7Eisenberg et al.) *>>A :
Anderson and !ohnson) 2005 :

/omar and 8irby) 2005 : 5indle et al.) 2005 9 in#luding
endometriosis,asso#iated

symptoms 7/o+ et al.) 200C : Dugh,erman and 8ronenberg)
200C 9.

Eviden#e for the potential effi#a#y of medi#inal herbs in the

treatment of
endometriosis,asso#iated symptoms has been reported

in the literature and is the fo#us of
this revie%.

Background

5raditional medi#ine pra#ti#es refer to health
approa#hes) kno%ledge

and beliefs in#orporating natural
plant) animal and mineral,based

medi#ines) spiritual
therapies) manual te#hni6ues and e+er#ises

7/hen and
/hen) 200? : -uang) *>>A 9. 5hese #an be applied
individually

or in #ombination to treat and prevent
illnesses or maintain

%ell,being. 'n industriali2ed
#ountries) adaptations of traditional

medi#ine are termed
#omplementary and alternative medi#ine 7/A.9.

/A.
is popular in all regions of the developing %orld and its

use is rapidly spreading in industriali2ed #ountries. 'n
Europe

and North Ameri#a) over 50< of the population have used /A.

at least on#e
75indle et al.) 2005 9.

-istori#ally) /hinese #ulture has relied heavily on herbal treatment

of many illnesses.
5raditional herbal preparations still a##ount

for C0150< of the total medi#inal
#onsumption in /hina.

3ritten re#ords do#ument the use of /hinese herbal medi#ine

over
C000 years ago. 'n /hinese medi#ine) endometriosis is #alled

Neiyi and is #onsidered a
Glood stasis syndromeH

resulting in the formation of endometrioti# lesions 7Dla%s)

*>A>
: .a#io#ia) *>>= 9. /hinese herbal formulae designed for

endometriosis therapy are
targeted to resolve blood stasis.

&espite #enturies of use abroad) medi#inal herbal
treatments

for endometriosis,asso#iated symptoms %ere only introdu#ed in

the (SA in
the mid,*>A0s. Several medi#inal herbs that histori#ally

%ere pres#ribed for treatment of
endometriosis,asso#iated symptoms

are still in use today 7/hen and /hen) 200? : -uang)
*>>A 9 75able *9.

Ea#h of the herbs des#ribed is likely #omposed of several a#tive

TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
#omponents %ith anti,inflammatory) anti,proliferative and pain,alleviating

properties
75able 29. 5hus) the potential for multiple

synergisti# intera#tions is enormous.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table '& .edi#inal herbs and natural #ompounds used in the
treatment of endometriosis and their bio#hemi#al #onstituents

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table (& .edi#inal herbs and natural #ompounds used in the
treatment of endometriosis and their anti,inflammatory effe#ts

Clinical evidence on the efficac$, to)icit$ and herb*
drug interactions of medicinal herbs and herbal
combinations used in the treatment of endometriosis

3e sear#hed .edline 7*>;> to November 200;9)
E.ASE 7*>A? to

April 200;9 and hand sear#hed
several prominent journals published

in /hina. /lini#al
eviden#e on the effi#a#y of herbal #ombinations

in
treatment of endometriosis is almost e+#lusively
published

in the /hinese s#ientifi# literature. As /hinese
medi#ine traditionally

uses mi+tures of medi#inal plants)
synergisti# as %ell as interfering

effe#ts may o##ur. 5he
#on#ept of synergisti# intera#tion refers

to the possibility
that %hen t%o 7or more9 a#tive substan#es

are given
#on#urrently) the substan#es may intera#t enhan#ing

the
effe#t of the other and at lo%er doses. Alternatively)
multiple

#ompounds #ould result in de#reased effi#a#y.
TOP
Abstract
Introduction
Background
Clinical evidence on the...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
5hese possible

intera#tions bet%een t%o or more drugs4herbs are #lassified

into
pharma#okineti# and pharma#odynami# effe#ts 7-arrison and

Dau#i) *>>A 9. E+amples
of medi#inal herbal #ombinations that

have been used to treat endometriosis,asso#iated
symptoms in#ludeK

danLe re#ipe) $e+ia Mhuyu 5ang) 8eishi,bukuryo,gan 78$9) Neiyi

re#ipe N*) Neiyi re#ipe N2) Neiyi+iao re#ipe) Shi+iao San 7Sudden

Smile Bo%der9) Shaofu
Mhuyu 5ang) Shi+iao $uijie 5ang) 5aoren

/hen6i 5ang) 5ongjin San) 5uo .o 5ang) 5ao
-e /heng 5ang) 0uefu

Mhuyu 5ang) 0iao Oao San) Oi 3ei Mhu Ou Dang and Oi%eining
7O3N9

7Shao) *>A0 : /ai) *>A2: &ai) *>A2 : /ao) *>AC : Eiu et al.) *>AC :

Ein et al.)
*>AA : Mhuang and 0ia) *>>0 : !in) *>>*: Ei) *>>* :

3ang et al.) *>>* : Fu) *>>2 : Ou
et al.) *>>C : Eiu) *>>? : -u

and Ei) *>>5 : Eiu et al.) *>>A : 3ang et al.) *>>A : /ai et
al.)

*>>> : Oang et al.) 200;a 9 75able C9.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table +& /lini#al studies on herbal #ombinations used in the
treatment of endometriosis

(nfortunately) the standards of eviden#e,based prin#iples are

sporadi#ally applied in
published #lini#al studies in this area.

Bublished trials of medi#inal herbs #on#erning
endometriosis

in the /hinese s#ientifi# journals of #omplementary medi#ine

have
generally not been #ondu#ted a##ording to the guidelines

of eviden#e,based medi#ine in
3estern s#ientifi# journals. "ne

of the major diffi#ulties in studying the #lini#al effe#ts of
herbal #ombinations in respe#t to eviden#e,based standards is

that the #omposition of
herbal formulae is individuali2ed for

ea#h patient a##ording to the different syndromes of
endometriosis

7Gblood stasis syndromeH9. "nly one randomi2ed #ontrolled

trial on the
potential effe#ts of medi#inal herbs in endometriosis

%as identified after a thorough
sear#h in the English literature

75able C9 7Oang et al.) 200;a 9. 5his study demonstrated

that O3N 7#onsisting of /hinese angeli#a) #orydalis) #ur#uma)

persi#a) red peony)
safflo%er) salvia root and tortoise shell9

%as safe and its effi#a#y %as similar to
gestrinone in the prevention

of post,operative re#urren#es of endometriosis. "ther trials

have been published only as personal #ommuni#ations or as #lini#al

observations in the
English literature. At present) a randomi2ed

#ontrolled trial is in progress in the (SA
evaluating the use

of traditional /hinese medi#ine 75/.9 at the 3omenLs -ealth

@esear#h (nit of the "regon -ealth S#ien#es (niversity and the

"regon /ollege of
"riental .edi#ine. 5he proto#ol 7N/5000C?0?= I/lini#al5rials.govJ 9

is funded by the
National /enter for /A. 7N//A.9. 5he study

tests the hypothesis that 5/.
7a#upun#ture and medi#inal herbs9

%ill redu#e endometriosis,related pelvi# pain as
effe#tively

as nafarelin therapy %ithout #ausing the pseudo,menopausal side

effe#ts that
a##ompany $n@-,a therapy. 3omen %ere randomly assigned

to re#eive either *2
%eekly treatments of 5/. or *2 %eeks of

the D&A,approved $n@-,a treatment. 5his
%ill likely prove to

be a landmark study in alternative endometriosis therapy.

&espite promising kno%ledge supporting the potential effi#a#y

of herbal treatments in
endometriosis and reports on the effi#a#y

of medi#inal herbs in related #onditions 7e.g.
over A0< of pain

relief) 5able C9) the #lini#al effe#ts of medi#inal herbs

on endometriosis
remain un#lear. Nevertheless) postulated e+perimental

me#hanisms of medi#inal herbs
in#lude demonstrated #ytokine

suppression) /"0,2 inhibition and antio+idant and
antino#i#eptive

a#tivities. 5reatment of endometriosis,asso#iated symptoms %ith

non,
hormonal regimens is a parti#ularly interesting treatment

option for adoles#ent %omen
%ith endometriosis. -ormonal anti,endometriosis

therapies su#h as $n@-,a) progestins
and oral #ontra#eptives

bear potential serious side effe#ts) %hi#h limit their use in

adoles#ents. As the effi#a#y of NSA'&s in %omen %ith endometriosis

remains un#lear)
non,hormonal treatment of symptoms %ith medi#inal

herbs or herbal #omponents may
represent an innovative alternative

for adoles#ents %ith endometriosis. .oreover) sin#e
herbal medi#ines

may e+ert synergisti# effe#ts) these #ombinations may #arry

potential
benefits of higher effi#a#y %hile minimi2ing to+i#ity.

Toxicity and herbdrug interactions
5here is a potential for to+i#ity and unto%ard herb1drug

intera#tions using medi#inal
herbs in the treatment of endometriosis

75able ?9. Eviden#e on to+i#ity and herb1drug
intera#tions

of medi#inal herbs used in the treatment of endometriosis is

limited 7-oskins)
*>A? : .oing et al.) *>A= : Berry et al.) *>>0 :

5akasuna et al.) *>>5 : 8uboni%a et al.)
*>>> : Bage and Ea%ren#e)

*>>> : 'shihara et al.) 2000 : Ei et al.) 200* : Amato et al.)

2002 : /hainani,3u) 200C : Elinav and /hajek,Shaul) 200C : 'kegami

et al.) 200C :
!oshi et al.) 200C : 3ong and /han) 200C : /hen

and /hen) 200? : 3oj#iko%ski et al.)
200?a )b: Mhou et al.) 200? :

de oer et al.) 2005 : -u et al.) 2005 : 8elly et al.) 2005 :
Ammon)

200; : Eao et al.) 200; : 0ie et al.) 200; 9 75able ?9. 5o+i#ity

and unto%ard
herb1drug intera#tions depend on fa#tors

asso#iated %ith drugs 7dose) dose regimen and
therapeuti# range9

and as %ell as the #onsumer 7age) geneti# polymorphism) gender

and
pathologi#al #onditions9. 5o+i#ity and herb1drug intera#tions

are unlikely to be evaluated
be#ause of the la#k of #urrent

federal regulations in some industriali2ed #ountries)
in#luding

the (SA) and the pau#ity of resear#h funding in this area. Established

monitoring of adverse events #aused by herb1drug intera#tions

and in#reased finan#ial
support for studies investigating herb1drug

interferen#e %ould provide #ru#ial
information regarding publi#

safety.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table ,& 5o+i#ity and intera#tions of medi#inal herbs used in the
treatment of endometriosis 7and typi#al #lini#al doses9

Effects of medicinal herbs, their active comonents
and herbal combinations on c$tokine e)ression

Suppression of the ND,8appa path%ay and pro,
inflammatory #ytokines

has been re#ogni2ed as a major
me#hanism of #onventional drug

treatments for
endometriosis: progestogens) $n@-,a) dana2ol

and
NSA'&s are kno%n to demonstrate #ytokine,suppressive
a#tivity

7ou#her et al.) 2000 : Mhao et al.) 2002 :
3ieser et al.)2005# :

Oang et al.) 200;b 9. /ytokines
and #hemokines su#h as tumour

ne#rosis fa#tor 75ND9,
alpha) interleukin 7'E9,*) 'E,;) 'E,A)

mono#yte
#hemota#ti# protein 7./B9,* and regulated on
a#tivation)

normal 5 #ell e+pressed and se#reted
7@AN5ES9 #ontribute to

the pathogenesis of endometriosis by enhan#ing atta#hment)
angiogenesis

and4or proliferation of e#topi# endometrial tissues in the pelvis

7erg6vist
et al.) 200* : Eebovi# et al.) 200* : .aas et al.)

200* 9.

/ur#uma 2eodaria is used in many anti,endometriosis formulae

7Shao) *>A0 : /ai) *>A2:
Ein et al.) *>AA : !in) *>>*: Fu) *>>2 :

-u and Ei) *>>5 : /ai et al.) *>>> : Eiu et al.)
200; : Oang et

al.) 200;a 9. /ur#uma 2eodaria belongs to the plant family
Mingibera#eae)

%hi#h #onsists of A0 different /ur#uma spe#ies su#h as /ur#uma

longa
7turmeri#9. /ur#umin is a major a#tive #omponent of /ur#uma.

5here are substantial
in vitro and animal data indi#ating

that #ur#umin has anti,inflammatory a#tivity 78umar
et al.)

*>>A : Siddi6ui et al.) 200; 9. /ur#umin %as sho%n to suppress

the ND,8appa
path%ay and ND,8appa target #ytokine genes 75akada

et al.) 200? 9 75ables *) 2) 59.
/ao et al. demostrated

anti,inflammatory effe#ts of #ur#umin in endometrial stromal

#ells: #ur#umin inhibited ND,8appa indu#tion of a pro,inflammatory

and angiogeni#
#ytokine) the ma#rophage migration inhibitory

fa#tor 7.'D9 in this endometriosis in vitro
model 7/ao et al.)

2005 9. @e#ent studies #ould #orroborate that #ur#umin arbitrates

the
effe#ts by modulation of several important mole#ular targets)

in#luding ND,8appa
mediated gene e+pression 7e.g. 5ND) 'E,*)

'E,;9) other trans#ription fa#tors 7e.g. AB,*)
Egr,*) beta,#atenin

and BBA@,gamma9) en2ymes 7e.g. /"02) iN"S9) re#eptors 7e.g.

E$D@ and -E@29 and #ell #y#le proteins 7e.g. #y#lin &* and p2*9

7Shishodia et al.)
2005 9. Substantial resear#h has sho%n for

other anti,endometriosis herbs 7e.g. /hinese
angeli#a9 that

they modulate #ytokine se#retion) in#luding 5ND,alpha as demonstrated

in
a variety of model systems 75seng and /hang) *>>2 : Eee et

al.) *>>5 : !ang et al.) 200*
: Van &ien et al.) 200* : 0u et al.)

2002 : 5ipton et al.) 200C : /hen and /hen) 200? :
Syrovets et

al.) 2005 : Eiu et al.) 200; 9 75able 59. .oreover) herbal

#ombinations %ere
sho%n to e+ert #ytokine 7e.g. 5ND,alpha) 'E,;)

'E,A9 suppressive effe#ts studied in
animal models of endometriosis

7Ou et al.) 2000 : Fu et al.) 2005 9. "ne e+ample is
O3N) a traditional

anti,endometriosis formula 75able C) 59) %hi#h de#reased

serum
#ytokine levels 7e.g. 5ND,alpha) 'E,; and 'E,A9 in a rodent

model of endometriosis 7Fu
et al.) 2005 9.

TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
Effects of medicinal herbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table -& /ytokine suppressive effe#ts of medi#inal herbs and
herbal formulae used in endometriosis

A sophisti#ated ne% approa#h to #reate novel) lo%,to+i#ity anti,inflammatory

drugs is to
design #hemi#al analogues of naturally o##urring

medi#inal herbal #ompounds. Dor
e+ample) ne%ly developed syntheti#

analogues of #ur#umin 7e.g. ED2?,tripeptide
#hloromethyl ketone9

have been introdu#ed to treat #an#er and #hroni# inflammatory

diseases 7Selvam et al.) 2005 : "hori et al.) 200; : Sun et al.)

200; 9. 5his alternative
approa#h to target key #ytokines may

establish drugs that la#k the deleterious side effe#ts
of #onventional)

as %ell as potential) endometriosis drugs su#h as anti,5ND biologi#als.

Anti,5ND protein therapeuti#s %ere sho%n to have potentially

severe side effe#ts su#h as
serious infe#tion and to indu#e

drug resistan#e in treated patients 78enter and /ohen)
200; :

S#ott and 8ingsley) 200; 9. .edi#inal herbs or designed syntheti#

analogues of
#omponents of herbs %ith #ytokine,modulating effe#ts

may provide lo%,to+i#ity
alternatives to treat endometriosis,asso#iated

symptoms 7Adams et al.) 200? 9.

Effects of medicinal herbs, their active comonents
and herbal combinations on the rostanoid ath"a$

5he prostanoid path%ay is suggested to be one of the key targets

involved in the
pathogenesis of endometriosis. Eo#ally produ#ed

B$E
2
) a
potent stimulator of aromatase) upregulates estrogen

produ#tion) %hi#h in turn stimulates /"0,2 to in#rease
B$E
2

leading to in#reased endometrial #ell proliferation
in endometriosis

7Noble et al.) *>>= : Attar and ulun)
200; 9. /"0,2,sele#tive

inhibitors %ere sho%n to e+ert
anti,proliferative effe#ts 7-asega%a

et al.) 2005 9) to
de#rease implant si2e in rodent models of

endometriosis
7&ogan et al.) 200? : .atsu2aki et al.) 200? 9 and

to
diminish endometriosis asso#iated,pain in a #lini#al
setting

7/obellis et al.) 200? 9. Among medi#inal anti,
endometriosis

herbs that inhibit the prostanoid system)
dahurian angeli#a

root) #innamon) li#ori#e root) poria)
s#utellaria) /ur#uma and

the formulae 8$) O3N and
Neiyi have been best studied 73ang

et al.) *>>* : .ori et al.) *>>C : Ou et al.) *>>C :
3ang et al.)

*>>A : $iner,Ear2a et al.) 2000 : Bark et al.) 200* : -ong et al.)

2002 :
TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
Effects of medicinal herbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
-uss et al.) 2002 : an et al.) 200C : Brieto et al.) 200C :

Duruhashi et al.) 2005 : Fu et
al.) 200; 9 75able ;9. /innamon

and poria) both e+hibiting /"0,2 suppressive a#tivity)
are #omponents

of the anti,endometriosis herbal formula 8$ 7#onsisting of

five
different herbs #innamon) poria) red peony) persi#a and

tree peony bark9. 5reatment %ith
the 8$ formula suppressed

spontaneous development of adenomyosis in a murine
endometriosis

model 7.ori et al.) *>>C 9. 5he benefi#ial effe#ts of 8$ in

the murine
endometriosis model may be attributed to the /"0,2

inhibiting effe#t of 8$Ls
#onstituents poria and #innamon.

O3N) an herbal #omposition 7/hinese angeli#a)
#orydalis) #ur#uma)

persi#a) red peony) safflo%er) salvia root) tortoise shell9

75able ;9)
redu#ed e+pression of /"0,2 m@NA in endometrioti#

tissues in a rat model 7Fu et al.)
200; 9. Durthermore) the anti,endometriosis

herbal re#ipe Neiyi 75able ;9 de#reased
prostaglandins

7e.g. B$E
2)
BgD
*
,alpha9 levels in #lini#al settings in %omen

%ith
endometriosis 73ang et al.) *>>* : 3ang et al.) *>>A : 3u

et al.) 2000 9.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table .& Suppressive effe#ts on the prostanoid path%ay of medi#inal
herbs and #ombinations used for endometriosis

5he highly regulated en2yme /"0,2) %hi#h #ataly2es prostaglandin

produ#tion) has
be#ome a popular target for the development

of ne% anti,inflammatory drugs. -o%ever)
some of the /"0,2 sele#tive

NSA'&s possess gastrointestinal side effe#ts. 'n addition)
re#ent

data suggest that #hroni# use of /"0,2 inhibitors is asso#iated

%ith in#reased
#ardiovas#ular risk 7Vonkeman et al.) 200; 9.

As a #onse6uen#e) some of the /"0,2
sele#tive NSA'&S %ere labelled

%ith bla#k bo+ %arning or %ithdra%n from the market.
'n the

light of re#ent reports of serious unintended effe#ts and bla#k

bo+ %arnings of
/"0,2 sele#tive drugs) plants %ith dire#t or

indire#t suppressive effe#ts on prostanoids
7-uss et al.) 2002 9

represent a potential alternative resour#e of /"0,2 sele#tive

inhibitors.

Effects of medicinal herbs, their active comonents
and herbal combinations on o)idative status

@ea#tive o+ygen spe#ies 7@"S9 are suggested to play a
role in

the pathogenesis of endometriosis 7.urphy et al.)
*>>A 9. @etrograde

menstruation allo%s transport of pro,
o+idant fa#tors) su#h as

heme) iron and apoptoti#
endometrial #ells) %hi#h are %ell,kno%n

indu#ers of
o+idative stress) into the peritoneal #avity of

%omen %ith
endometriosis 7Van Eangendon#kt et al.) 2002 9. @"S

#an promote gro%th of endometrial stromal #ells
7Doyou2i et

al.) 200? 9. Antio+idants) su#h as vitamin E)
sho%ed benefi#ial

effe#ts in an in vitro model of
endometrial proliferation 7Doyou2i

et al.) 200? 9 and
anti,inflammatory effe#ts in a rodent model

of EBS,
indu#ed inflammation leading to in#reased embryo viability

7.ayorga et al.) 200? 9.
&rugs %ith antio+idant properties) su#h

as SB@.s) have been developed as possible
treatment #hoi#es

for endometriosis 7@oberts et al.) *>>; 9) but #on#lusive eviden#e

on
the benefits of the various modalities is la#king.

/ommonly used Ganti,endometriosisL herbs su#h as /hinese

angeli#a) #ur#uma and salvia
root) turmeri# and herbal formulae

7e.g. 8$9 have potent anti,o+idant effe#ts 7/ao et
al.) *>>; :

Ooshioka et al.) *>>A : Fuiles et al.) 2002 : hou et al.) 200? :

8ang et al.)
200? : .oussaieff et al.) 2005 : Sekiya et al.) 2005 :

Mhou et al.) 2005 : El,Ashma%y et
al.) 200; 9 75able =9.

5he ability of 8$ and vitamin E to prevent atheros#lerosis

%as
#ompared in diet,indu#ed hyper#holesterolemi# rabbits 7Sekiya

et al.) 2005 9. 8$ had a
stronger anti,o+idant effe#t than vitamin

E sho%n in this animal model. 5he superiority
of the herbal

#ombination 8$ to vitamin E in this animal likely relates to

synergisti#
intera#tions %ithin the herbal #ombination.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table /& Antio+idant effe#ts of medi#inal herbs and herbal
#ombinations used in endometriosis

'n this #onte+t) it is note%orthy to mention that although in#reased

serum levels of
vitamin E levels %ere asso#iated %ith de#reased

risk for #an#er and #ardiovas#ular
diseases 7Stahelin et al.)

*>>* 9) e+ogenous oral administration of the antio+idant
vitamin

E did not sho% benefits in #an#er and #ardiovas#ular disease

in human
intervention studies 7ro%n et al.) 200* : Ei#htenstein

and @ussell) 2005 9. &ata from
the -"BE and -"BE,5"" trials sho%ed

that vitamin E did not de#rease fatal or non,
fatal #an#er 7Eonn

et al.) 2005 9. %itamin E alone also did not redu#e myo#ardial

infar#tion) stroke) /V& death and other #ardiovas#ular morbidities:

instead vitamin E
in#reased hospitali2ation for heart failure

7Eonn et al.) 2005 9. 'n #ontrast to these
TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Effects of medicinal herbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
findings) diets high

in vitamin E sho%ed benefi#ial influen#e on the in#iden#e on

#ardiovas#ular health and #an#er risk 78noops et al.) 200? :

Ei#htenstein and @ussell)
2005 9. 'n an elderly population 7=01>0

years9) adheren#e to a .editerranean diet and
healthful lifestyle

is asso#iated %ith a more than 50< lo%er rate of all,#auses

and #ause,
spe#ifi# mortality 7-AEE proje#t9 78noops et al.)

200? 9. 'n #ombination) these studies
7-"BE and -AEE proje#ts9

suggest that either vitamin E has limited or no benefit or
that

it has benefit only in #ombination %ith other food,related substan#es.

'n an 'talian
endometriosis population) higher intake of green

vegetables and fresh fruit #aused a
signifi#ant redu#tion of

the risk for endometriosis 7Bara2ini et al.) 200?9. 'nterpretation

of
nutritional studies on the effe#t of dietary patterns on

#an#er and #ardiovas#ular disease
prevention led to the definition

of the G%hole foodL #on#ept 75emple and $ald%in) 200C9.

Several #omponents in fruits and vegetables %ith benefi#ial

effe#ts are postulated to
prevent disease via their synergisti#

effe#ts. 5his Lteam%orkL prin#iple is likely to hold for
synergisti#

herbal therapies as %ell) but resear#h %ill be needed to delineate

optimal
#ombinations.

Anti-nocicetive of medicinal herbs, their active
comonents and herbal combinations used in the
treatment of endometriosis

5he #ellular and neural me#hanisms of pelvi# pain
asso#iated

%ith endometriosis are poorly understood
7$ambone et al.) 2002 9.

't has been proposed that dire#t
invasion of pelvi# nerves by

endometrioti# implants or
nearby release of inflammatory humoral

fa#tors 7e.g.
prostaglandins) #ytokines9 stimulate sensory and

parasympatheti# afferents that #arry the per#eived
painful stimuli

75ulandi et al.) *>>A 9. E#topi#
endometrial gro%ths themselves

develop autonomi# and
sensory innervations 7erkley et al.)

2005 9.

&rugs most #ommonly pres#ribed to treat endometriosis pain symptoms)

parti#ularly
dysmenorrhea) are NSA'&s) #ombined oral #ontra#eptives

7/"/9) and other analgesi#s
7e.g. para#etamol9. Eviden#e of

the effi#a#y of /"/ on dysmenorrhea remains to be
determined

7Bro#tor et al.) 200* 9) and there has been relu#tan#e to use

the /"/ at young
ages be#ause of possible long,term health risks.

5he eviden#e on the effi#a#y of NSA'&s
in the treatment of endometriosis

is in#on#lusive 7Allen et al.) 2005 9. .oreover) therapy
%ith

NSA'&s #an bear side effe#ts. 3omen using NSA'&s and even over

the #ounter
painkillers su#h as a#etaminophen need to be a%are

of the possibility that these drugs
may #ause serious unintended

effe#ts in#luding in#reased risk of #ardiovas#ular events)
hypertension

and gastri# ul#eration 7&edier et al.) 2002 : Dorman et al.)

2005 : !ohnsen
et al.) 2005 9.

TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocicetive of medicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
Sin#e an#ient times) herbal medi#ine has been used to relieve

pain and dis#omfort from
%ounds and burns. Eviden#e #onfirms

pain alleviating me#hanisms of several medi#inal
herbs used

for endometriosis 7e.g. #nidium fruit) #orydalis) #ur#uma) dahurian

angeli#a)
frankin#ense) myrrh and %hite peony root9 and herbal

formulae 7e.g. Neiyi9 75uttle et al.)
*>A> : Eiu et al.) *>>0 :

Ou et al.) *>>C : Ou et al.) *>>5 : &olara et al.) *>>; : 3ang

et
al.) *>>A : 3ei et al.) *>>> : Mhang et al.) 2000 : 5sai et

al.) 200* : Navarro &de et al.)
2002 : 8immatkar et al.) 200C :

5atsumi et al.) 200? : Ouan et al.) 200? : Mhou et al.)
2005 9

75able A9.

%ie" this
table&
Iin this
%indo%J
Iin a n e %
%indo%J

Table 0& Anti,no#i#eptive effe#ts of medi#inal herbs and
#ombinations used in endometriosis

/orydalis is one of the most #ommonly used herbs in pain related

syndromes 7/hen and
/hen) 200? 9) and is also used in many /hinese

formulae designed for the treatment of
endometriosis,asso#iated

pain 7&ai) *>A2 : /ao) *>AC : Ein et al.) *>AA : !in) *>>*: Fu)

*>>2 : 3ieser et al.)2005a )b: Oang et al.) 200;a 9 75able C9.

5etrahydropalmatine
75-B9 is thought to be the main a#tive pharma#ologi#al

#omponent of #ordyalis 7ro%n
et al.) 200* 9: 5-B has been sho%n

to e+hibit anti,inflammatory) sedative) analgesi#)
hypnoti#

and mus#le rela+ant properties sho%n in vitro and rodent models

73ei et al.)
*>>> : /hen and /hen) 200? 9.

Anti,no#i#eptive /A. treatments are gaining in#reased popularity

for treatment of
d$smenorrhoea in industriali2ed #ountries 7Dugh,erman

and 8ronenberg) 200C 9.
5herapies sho%n to be potentially effe#tive

in the treatment of d$smenorrhoea in#lude
vitamin E 7utler

and .#8night) *>55 9) vitamin * 7$okhale) *>>; : 3ilson and
.urphy)

200* 9 and ,C fatty a#ids 7fish oil9 7&eut#h) *>>5 9. "ne randomi2ed

#ontrolled trial %as #ondu#ted to evaluate the effi#a#y of an

herbal #ombination
#onsisting of #orydalis) /hinese angeli#a

and %hite peony root on the effi#a#y of
d$smenorrhoea 78ennedy

et al.) 200; 9: ho%ever) the sample si2e of this trial %as too

small. -erbal therapy may serve as a potential alternative espe#ially

for young adults %ith
endometriosis,asso#iated pain syndromes.

!iscussion

A signifi#ant in#rease in lifetime use of herbs and other
natural

produ#ts %as noted from *2.*< to *A.;<
bet%een *>>A and 2002

in the (SA 75indle et al.) 2005
9. "n *; .ay 2002) the 3-" released

its first global
strategy on traditional medi#ines and announ#ed

that it
%ill be greatly e+tending its a#tivities in non,allopathi#

therapies. Several important drugs are derived from
natural

produ#tsK aspirin 7*AA>: from %illo% bark9)
peni#illin 7*>?0s:

from fungus9) artemisinin 7*>A0: from
6uinghaosu9) meva#or 7*>A=:

from fungus9) ta+ol 7*>>C:
from the pa#ifi# ye% tree9 and byetta

72005: from $ila
monster saliva9. 't is hoped that medi#inal

herbs or #ombinations of medi#inal herbs and
drugs %ill promote

health and %ell being) %hile minimi2ing to+i#ities and side

effe#ts.

Alternative pain therapies have gained popularity parti#ularly

among %omen %ith
endometriosis. 't is predi#ted that /A. %ill

be used in #ombination %ith allopathi#
medi#ine or %ill #ompletely

repla#e standard pharma#ologi#al options for some %omen
%ith

endometriosis as sho%n in an Australian population 7/o+ et al.)

200C 9. &espite the
la#k of rigorous eviden#e) many re#ipients

of herbal therapy vie% these natural produ#ts
to be safer and

more effe#tive alternatives to 3estern medi#ine. "ther /A. users

believe them to be more #ompatible %ith their beliefs even if

they are less effi#a#ious
than #onventional therapy 7Astin et

al.) 2000 9. 'n vie% of the need for alternatives in
pain management)

/A. therapies su#h as medi#inal herbs and other botani#als %ith

anti,
inflammatory and pain,alleviating properties may be useful

parti#ularly in the treatment
of endometriosis,asso#iated symptoms.

-erbal medi#ine has been pres#ribed safely by
professionals

in the (SA for many years: ho%ever) there are only fe% formal

studies on
safety and effi#a#y of #ombining herbal #ombinations

%ith pres#ription drugs.

Although #lini#al studies on herbs in the literature sho% promising

effe#ts) #on#lusive
#lini#al eviden#e of the effi#a#y of medi#inal

herbs in the treatment of endometriosis,
asso#iated pain is la#king.

5he effe#ts of /hinese herbal medi#ine for treating
endometriosis

remain un#lear for several reasons. Dirst) most herbs #urrently

used in
human populations have been available for the last 2000

years and no effi#ient regulation
me#hanisms #ontrol their use

73olsko et al.) 2005 9. Sin#e *>>?) phytomedi#inal
produ#ts 7medi#ines

derived from plants9 are legally #lassified in the (SA as dietary

supplements. 'n#luded in this #ategory are vitamins) minerals)

herbs or other botani#als)
amino a#ids and other dietary substan#es

derived from animals or plants. 5he (S Dood
and &rug Administration

la#ks 6uality standards 7&e Smet) 2005 9 and does not re6uire

levels of therapeuti# eviden#e in the form of randomi2ed #lini#al

trials before su#h
produ#ts are marketed to #onsumers. Some

European #ountries) su#h as $ermany and
Dran#e) %ere among the

first to introdu#e simplified registration pro#edures for herbal

produ#ts. 'n order to harmoni2e different registration pro#edures)

the European
parliament has installed spe#ifi# regulatory me#hanisms

#overing medi#inal herbal
produ#ts 7&e Smet) 2005 9. &ire#tive

200?42?4E/ re6uires a spe#ial) but simplified
registration pro#edure

for #ertain medi#inal produ#ts 7&e Smet) 2005 9. 'n addition)

European legislation introdu#ed a list of re#ogni2ed herbs and

mandates adverse,event
reporting. Se#ondly) spe#ifi# me#hanisms

of a#tion of herbs are underreported and have
TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
not been tested

using appropriate study designs in#luding in vitro and animal

models
7/ao et al.) 2005 : Fu et al.) 2005 : 3ieser et al.)2005b 9.

Dinally) single herbs 7e.g.
/ur#uma9 and herbal #ombinations

are #omposed of a number of bioa#tive #ompounds)
#ompli#ating

the investigation of their me#hanisms of a#tions. enefits of

the inherent
synergism %ithin single herbs and herbal #ombinations

are enhan#ed effi#a#y and
redu#ed to+i#ity. "f #ourse) liabilities

are also possible as some intera#ting substan#es
might #ompete

%ith ea#h other or in#rease to+i#ity. 5he potential for both

positive and
negative intera#tions ne#essitates #areful study

and validations of e+isting and ne%
permutations.

'nvestigations of the effi#a#y) to+i#ity and herb1herb

and drug1herb intera#tions should
in#lude testing in in

vitro and rodent 7e.g. rat9 models and subhuman primate models

7e.g. baboon9 of endometriosis 7@yan et al.) *>>? : &L-ooghe)

*>>= : A%%ad et al.)
*>>> : Da2leabas et al.) 2002 9. .oreover)

investigators should be en#ouraged to provide
information on

the purity) 6uality and #omposition of the herbs tested in e+perimental

trials. Standardi2ation %ould enhan#e interpretation of /A.

data and thus the
appli#ability of the findings. After a#6uiring

me#hanisti# and safety data) %e propose that
randomi2ed #lini#al

trials be planned and implemented using human subje#ts %ith

endometriosis. Adoles#ents %ith endometriosis are the most likely

to benefit from disease
prevention) preservation of fertility

and pain relief %ith innovative herbal treatments. 5he
use of

standard Lsingle drugL hormonal endometriosis regimens 7e.g.

$n@-,a) dana2ol
and progestagens9 is most likely to have unto%ard

side effe#ts and long,term morbidities
in this important patient

population.

Conclusion

"ver the ne+t 20 years) major shifts are likely to o##ur in

the use of herbal #ompounds) vitamins) minerals)
supplements)

nutra#euti#als or %hole food nutrition. 3e
should anti#ipate

a %ave of ne% natural medi#ines based
on s#ientifi#ally substantiated

health #laims. 'n the near
future) %e predi#t that more (S adults

%ill use medi#inal
herbs and herbal produ#ts to treat their

diseases as %e
#hange our perspe#tive from treating disease

to
promoting better health. Dormal #lini#al trials testing the

me#hanisms of a#tion) effi#a#y and to+i#ities of /A.
therapies

are needed. 5he establishment of the N//A.
'nstitute of the

N'- %as an important step to%ards the
validation of popular

and effe#tive traditional treatments 7Stokstad) 2000 9. &espite

the
limited gro%th in the N'-) the Dis#al Oear 7DO9 200; BresidentLs

budget for the N//A.
in#reased to P*22 ;>2 000. N//A. has sponsored

several #lini#al trials on the effi#a#y
of medi#inal herbs in

the treatment of irritable bo%el syndrome) menopausal symptoms)

hepatitis /) A'&S and #an#er.

TOP
Abstract
Introduction
Background
Clinical e vid e nc e on th e ...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
E ff e cts of m e dicinal h e rbs,...
Anti-nocic e tiv e of m e dicinal...
!iscussion
Conclusion
Ackno"l e dg e m e nts
# e fe r e nc e s
/ontrolled #lini#al studies %ill be needed to #larify the #lini#al

effi#a#y of natural
medi#inal herbs or syntheti# herbal analogues

in the treatment of endometriosis,
asso#iated pain and investigate

herb1herb and drug1herb intera#tions and other
to+i#ities.

A potential benefit of herbal therapy is the likelihood of synergisti#

intera#tions
%ithin individual 7e.g. /ur#uma9 or #ombinations

of plants and the #onstraint of
unto%ard side effe#ts. E+perimental

and epidemiologi#al data 7e.g. -"BE and -AEE
trials9 infer that

health promotion involves addressing many important determinants

rather
than adjusting the level of a single substan#e. 3e) therefore)

believe that it is #riti#al to
establish streamlined registration

pro#edures for natural medi#inal produ#ts) parti#ularly
herbal

ones that have a long tradition of safe use