Review ArticleA Literature Review of Womenrsquos Sex Hormone Changes byAcupuncture Treatment Analysis of Human and Animal Studies

Jade Heejae Ko and Seung-NamKim

College of Korean Medicine Dongguk University Goyang 10326 Republic of Korea

Correspondence should be addressed to Seung-Nam Kim snkimdonggukedu

Received 7 August 2018 Accepted 7 November 2018 Published 15 November 2018

Academic Editor Stephanie Tjen-A-Looi

Copyright copy 2018 Jade Heejae Ko and Seung-Nam Kim This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Background It has been known that acupuncture treatment relieves gynecological disorders such as menopause ovariandysfunction and dysmenorrhea Sex hormones including estrogen progesterone and gonadotropins are related to the womendisease However regulative effect of acupuncture on sex hormones has not been fully identified Methods Acupuncture articlesincluding analysis of sex hormones were searched in electronic databases from inception to June 2018 The methodological qualitywas assessed using modified CAMRADES tool A total of 23 articles were selected and analyzed Results In the results overallstudies showed that acupuncture increases estrogen especially estradiol progesterone prolactin and other hormones Estradiollevel was increased in most of studies except 3 studies which resulted in decreased level or not meaningful change Two studiesshowed increase of FSH and LHwhereas it was decreased in other studies Other hormones were mostly increased by acupunctureConclusion This study possibly indicates that acupuncture changes sex hormone in various gynecological conditions in women

1 Background

Female reproductive health is closely related to menstrualcycle and menstrual health The causes of gynecologi-cal disorders reproductive dysfunctions and menopausalsyndromes such as polycystic ovarian syndrome (PCOS)dysmenorrhea and hot flush were suggested in numerousstudies The cause of the gynecological issues is mainlyimbalance of sex hormones [1ndash4] in addition to extrinsicfactors [5] Along with the scientific findings in terms ofthe dysfunctions and symptoms various treatment methodshave been used in patients Hormonal contraceptives havebeen used most widely and frequently for gynecologicaldisorders and reproductive dysfunctions [6] For instanceoral contraceptives pills (OCPs) which are known to regulatehyperandrogenism have been used to treat patients withPCOS andmenstrual dysfunctions [7]The efficacy and safetyof the OCPs were proven via numerous experiments andclinical trials Nevertheless a considerable proportion ofwomenwhohave ever takenOCPsdiscontinued takingOCPsdue to side effects such as weight gain headache and nausea[8]

For gynecological issues of women acupuncture hasbecome one of the popular complementary treatment meth-ods and use of acupuncture has been steadily increasing[9] It has been well understood that acupuncture is effec-tive in analgesia and blood flow regulation [10] Accordingto research women are more likely to use acupunctureas an adjunct treatment compared to men [11 12] Withincreased recognition of effect of acupuncture in many fieldof studies its effects on gynecological and reproductive issueswere raised among people Therefore in present review weexplored how acupuncture affects and changes different sexhormone levels in animal model and human

2 Methods

21 Eligibility Criteria All eligible studies examined changesin follicle stimulating hormone (FSH) luteinizing hormone(LH) FSHLH progesterone estrogen prolactin or oxytocinlevel Acupuncture treatment involving hormone studieswere retrieved Studies that only used either electroacupunc-ture or manual acupuncture were enrolled while studieswhich used other acupoint stimulation method or moxibus-tion were excluded

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2018 Article ID 3752723 9 pageshttpsdoiorg10115520183752723

2 Evidence-Based Complementary and Alternative Medicine

22 Study Selection The following Pubmed EMBASE andCochrane Central Register of Controlled Trials (CEN-TRAL) were searched from inception until June 2018 Thesearch terms included the following ([acupuncture ORelectroacupuncture] AND [follicle stimulating hormone ORluteinizing hormone OR progesterone OR estrogen ORprolactin OR oxytocin OR reproductive hormone]) Thesearching of the electronic databases led us to identify 124potentially relevant manuscripts The titles and abstracts thatmet the criteria of our study were independently read bytwo reviewers and only complete manuscripts published inEnglish were retrieved A total of 101 articles were excludedand the exclusion criteria were as follows (1) full texts notaccessible (2) review article (3) use of other acupoint stim-ulation or moxibustion (4) case report (5) letter (6) irrele-vance in terms of hormone study and (7) irrelevance in termsof acupuncture study 23 studies were included ultimately

23 Quality Assessment The methodological quality of eachincluded study was assessed by two authors (Kim and Ko) byusing 8-item checklist modified from CAMARADES check-list [13 14] (1) peer-reviewed manuscript (2) explanation ofacupuncture procedure (3) detailed description of condition(4) detailed statement of sample (5) detailed explanation ofsampling method (6) statement of screened hormone type(7) compliance with experiment subject welfare regulationand (8) statement of potential conflict of interests A sum ofquality score was recorded for each article and possible totalscore was 8 points

3 Results

31 Search Result A total of 124 publications were initiallyidentified in Pubmed EMBASE and Cochrane Central Reg-ister of Controlled Trials (CENTRAL) from their inceptionto June 2018 Among the initial 124 publications 22 articleswere excluded because their full-texts were unobtainable and5 duplicate recordswere also excluded After title and abstractscreening total of 32 articles were excluded because theywerereviews case reports letters or other acupoint stimulationmethods 42 articles were excluded additionally after full-text screening and there were 28 nonhormone studies 4nonacupuncture 3 low-quality studies and 7 studies whichhad other reasons Among the 7 studies 2 studies usedanimals other than rat or mouse 1 study used herb astreatment 1 study was conducted with male patients andthe remaining three studies induced diseases by estrogenor progesterone 23 articles which satisfied the criteria ofour study were ultimately selected Our screening process issummarized as flow diagram in Figure 1

13 articles used electroacupuncture (EA) 7 articles usedmanual acupuncture (MA) 2 articles used both EA andMA and acupuncture method of one article was not able toidentify Of the 23 articles 11 articles used human as subjectand 12 articles used animal subject

32 Quality Assessment Table 1 shows quality assessmentof included studies The quality score of included studies

ranged from 4 to 8 out of a total 8 points The overallscore for the studies were high 9 studies scored 8 points[15ndash23] 10 studies scored 7 points [24ndash33] 2 studies scored6 points [34 35] and 2 studies scored 5 points [36 37]Of the 23 studies 21 studies were peer-reviewed 21 studiesincluded explanation of acupuncture procedures 22 studiesdescribed condition of experiment subject and all 23 studiesincluded detailed explanation of sample sampling methodand screened hormone type 22 studies mentioned compli-ance with experiment subject welfare regulations 9 studiesincluded potential conflicts of interest

33 Effect of Acupuncture on Estrogen Level We observedchanges of estrogen level by acupuncture treatment of the23 included studies (Table 2) Of the 23 studies 14 studiesinvestigated how acupuncture treatment affects changes inestrogen level solely or in addition to other female sexhormones 3 articles measured estradiol (E2) level change inpolycystic ovary syndrome (PCOS) models [15 16 24] E2level was decreased in 2 studies [15 24] while there was nomeaningful change in one study [16] E2 level was increasedin 5 ovariectomized rat model studies [17 18 27ndash29] Therewere 3 articles which measured E2 level in human withmenopausal syndrome [19 34 35] There was no meaningfulchange in estrogen level in two of the studies [34 35] whileone study showed increment of E2 level [19]

Wang et al and Zhou et al investigated effect of acupunc-ture on E2 level in human with diminished ovarian reserveand primary ovarian insufficiency respectively [20 22] E2level was increased in compliance with acupuncture treat-ment in the both studies

34 Effect of Acupuncture on FSH and LH Level Table 3shows 14 studies that examined effect of acupuncture andreported on the outcomes of FSH and LH level changesAmong the 14 studies 6 studies measured FSH level LH levelor FSHLH level in PCOSmodels [15 16 23ndash26] Maliqueo etal suggested that acupuncture rendered FSH level increasewhereas LH level and FSHLH level were decreased [23 24]Pastore et al also found that FSHLH level was upregulatedwith acupuncture treatment although there was no notablechange in FSH level and LH level [16] Changes in LH levelin most of the studies were found to be decreased or notsignificant

35 Effect of Acupuncture on Other Hormones In Table 4 10studies suggested effect of acupuncture on hormonal changesby measuring several other sex hormones progesterone[21 25 35] prolactin [21 26 35 36] human chorionicgonadotropin (hCG) [16 36] gonadotropin releasing hor-mone (GnRH) [29] oxytocin [31 37] and prolactin releasingprotein (PrRP) [27] Each hormone was examined solelyor along with FSH LH or estrogen 3 studies investigatedprogesterone level in different pathological conditions andthere was increment of progesterone level in the three studies[21 25 35] Furthermore other studies which examined pro-lactin hCG GnRH oxytocin and brain PrRP also suggestedincreased hormone level in compliance with acupuncturetreatment

Evidence-Based Complementary and Alternative Medicine 3

Records identified throughPublication searching

(n = 124)

Full-text not accessible (n = 22)Duplicate (n = 5)

Titleabstract screening(n = 97)

Records excluded (n = 32)

Review (18)Case report (4)Letter (1)Auricular acupuncture (4)Moxibustion (4)Laser acupuncture (1)

Full article assessment(n = 65 )

Records excluded (n = 42)

Non-hormone study (28)Non-acupuncture study (4)Low-quality (3)Other (7)

Studies included(n = 23)

Figure 1 Flow diagram of the review

4 Discussion

This review found that acupuncture potentially alters dif-ferent sex hormone levels in animal model and patientswith gynecological or reproductive issues It is evident thatacupuncture has been increasingly used in many diseasesand its effects are examined through studies in various fieldsKnowing that female population is high in number amongacupuncture users aim of understanding clinical significanceand effect of acupuncture on womenrsquos sex hormone hasbeen raised We examined change in womenrsquos sex hormonesestrogen progesterone oxytocin and gonadotropin hor-mones and searched evidence of hormones being regulatedby acupuncture A total of 23 studies were included for thereview and hormone level change was investigated for eachincluded study

Based on what we have found estrogen (estradiol) levelwas a mainly measured hormone in the articles and theincreased estrogen was detected in most of the studieswhile estrogen was decreased in the study of Maliqueo etal [23 24] and Johansson et al [15] As these two articlesstudied PCOS disease whereas other articles studied ovariandysfunction it is possible that increased estrogen level inovarian dysfunction and decreased estrogen level in PCOSare presumably influenced by disease characteristics

Gonadotropin hormone level was also investigated inmost of the studies to see whether acupuncture affectedhormone levels in animal model and patients In an earlyhormonal study Patel et al suggested that GnRH-stimulatedoversecretion of LH best elucidates cause of PCOS in women[38] Results were inconsistent among the studies therefore

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Quality assessment of studies included

Author Year Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 ScoreMaliqueo et al 2015 7Johansson et al 2013 8Feng et al 2012 7Pastore et al 2011 8Stener-Victorin et al 2000 7Ma et al 2017 8Qin et al 2013 8Yao et al 2007 7Zhao et al 2004 7Zhao et al 2003 7Sunay et al 2011 8Qu et al 2007 6Dong et al 2001 6Wang et al 2016 8Xiong et al 2015 8Zhou et al 2013 8Magarelli et al 2009 5Zhang et al 2007 7Gaudernack et al 2006 7Yang et al 2006 7Yang et al 2006 7Uvnas-Moberg et al 1993 5Zheng et al 2013 8

further studies are expected for better understanding of effectof acupuncture in terms of gonadotropins

Although there were comparatively less studies whichexamined other sex hormones progesterone oxytocin hCGPrRP prolactin and GnRH hormone level was increased asa result of acupuncture Among the studies prolactin levelwas found to be increased by acupuncture In several otherstudies prolactin is increased as a result of acupuncturetreatment [39 40] It seems that acupuncture potentiallyincreases prolactin level yet more mechanism studies areneeded in order to verify exact effect of acupuncture on sexhormones

In terms of acupuncture method there was insuffi-cient number of correlation identified between acupunc-ture method and hormone changes For instance estrogenlevel was increased by use of MA in the study of Sunayet al [19] and there was also increased estrogen level inthe study of Wang et al [20] by using EA By contrastLH level was decreased in the study of Ma et al [17]However the studies included in this review not only havebroad range of acupuncture method but also have differentacupuncture forms (manual or electroacupuncture) dura-tions of treatment acupuncture points and intensities (seein Supplementary Table 1) Such diversity of acupuncturemethod made drawing definite conclusion hardly possibleThus further study is required to understand the relationshipbetween sex hormones and acupuncturemethodMeanwhileeffect of homeostasis regulating effect of acupuncture may

elucidatemechanism inhormone changes It was studied howacupoint specificity affects hypothalamic-pituitary-adrenalcortex axis (HPAA) regulation In addition it was suggestedthat acupuncture altered stress reaction neurons in par-aventricular nucleus [41] One of the key factors in brainactivity and homeostasis regulation Neuropeptide Y (NPY)which is highly concentrated in hypothalamus is involvedin the regulation of various physiological functions suchas energy homeostasis and stress-related behavior processSeveral studies investigated effect of acupuncture on crit-ical physiological processes In diabetic rats acupuncturesuppressed NPY and it led to controlling hyperphagia [42]Anxiogenic-like behaviors in maternally separated rats werealso recovered to normal state and decreased NPY expres-sion was upregulated by acupuncture [43] Acupunctureprevented elevation of NPY expression which was inducedby cold stress [44] The hormonal changes were inconsistentamong same disease modelsThe inconsistency is consideredto be due to different reasons of disease and used acupointsIt is suggested to focus more on the fact that acupuncturemay restore the balance among the hormones rather thansolely focusing on increase and decrease of hormone levelTo suggest clinical implications of acupuncture in variousdiseases it is important to recognize that acupuncture mayhave bidirectional effect depending on diseases It alsoshould be considered what physiological context a diseasepotentially has in order to properly account for effect ofacupuncture

Evidence-Based Complementary and Alternative Medicine 5

Table2Ch

angesinestro

genby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

ber

Disease

Acup

uncture

Acup

uncture

metho

dof

sample

(exp

con

)compa

redto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998771E2

998810E2

EAJohanssonetal

2013

Hum

anPC

OS

1114

998810E1E

1-SE

2EA

+MA

Feng

etal

2012

Animal(rat)

PCOS

4044

998771E2

EA+M

AMae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998810E2

998771E2

EAQin

etal

2013

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAYaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAZh

aoetal

2004

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998810E2

998771E2

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

≒Estro

gen

MA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒E2

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998810

E2998771E2

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998810

E2998771E2

EA

Zhangetal

2007

Animal(rat)

Pubertal

developm

ent

54

998810E2

998771E2

EA

998771Increased998810

decreased

and≒no

tsignificant

6 Evidence-Based Complementary and Alternative Medicine

Table3Ch

angesinFSHandLH

byacup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

Acup

uncture

metho

dCom

paredto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998810FSH998771

LH

998771FSH998810

LH

998810FSHLH

EA

Johanssonetal

2013

Hum

anPC

OS

1114

≒FSH≒

LH

≒FSHLH

EA+M

A

Feng

etal

2012

Animal(rat)

PCOS

88

≒LH

EA+M

A

Pasto

reetal

2011

Hum

anPC

OS

4044

≒FSHLH

998771FSHLH

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24≒FSHLH

998810FSHLH

EA

Zhengetal

2013

Hum

anPC

OS

43998810

FSH998810

LH

998810FSHLH

MA

Mae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998771LH

998810LH

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998771FSH998771

LH

≒FSH

(p=0053)

998810LH

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

998810FSH≒

LHMA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒FSH(p

=004

)≒LH

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998771FSH998771

LH998810

FSH998810

LH

998771FSHLH

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998771FSH998771

LH998810

FSH998810

LHEA

998771Increased998810

decreased

and≒no

tsignificant

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

Evidence-Based Complementary and Alternative Medicine 3

Records identified throughPublication searching

(n = 124)

Full-text not accessible (n = 22)Duplicate (n = 5)

Titleabstract screening(n = 97)

Records excluded (n = 32)

Review (18)Case report (4)Letter (1)Auricular acupuncture (4)Moxibustion (4)Laser acupuncture (1)

Full article assessment(n = 65 )

Records excluded (n = 42)

Non-hormone study (28)Non-acupuncture study (4)Low-quality (3)Other (7)

Studies included(n = 23)

Figure 1 Flow diagram of the review

4 Discussion

This review found that acupuncture potentially alters dif-ferent sex hormone levels in animal model and patientswith gynecological or reproductive issues It is evident thatacupuncture has been increasingly used in many diseasesand its effects are examined through studies in various fieldsKnowing that female population is high in number amongacupuncture users aim of understanding clinical significanceand effect of acupuncture on womenrsquos sex hormone hasbeen raised We examined change in womenrsquos sex hormonesestrogen progesterone oxytocin and gonadotropin hor-mones and searched evidence of hormones being regulatedby acupuncture A total of 23 studies were included for thereview and hormone level change was investigated for eachincluded study

Based on what we have found estrogen (estradiol) levelwas a mainly measured hormone in the articles and theincreased estrogen was detected in most of the studieswhile estrogen was decreased in the study of Maliqueo etal [23 24] and Johansson et al [15] As these two articlesstudied PCOS disease whereas other articles studied ovariandysfunction it is possible that increased estrogen level inovarian dysfunction and decreased estrogen level in PCOSare presumably influenced by disease characteristics

Gonadotropin hormone level was also investigated inmost of the studies to see whether acupuncture affectedhormone levels in animal model and patients In an earlyhormonal study Patel et al suggested that GnRH-stimulatedoversecretion of LH best elucidates cause of PCOS in women[38] Results were inconsistent among the studies therefore

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Quality assessment of studies included

Author Year Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 ScoreMaliqueo et al 2015 7Johansson et al 2013 8Feng et al 2012 7Pastore et al 2011 8Stener-Victorin et al 2000 7Ma et al 2017 8Qin et al 2013 8Yao et al 2007 7Zhao et al 2004 7Zhao et al 2003 7Sunay et al 2011 8Qu et al 2007 6Dong et al 2001 6Wang et al 2016 8Xiong et al 2015 8Zhou et al 2013 8Magarelli et al 2009 5Zhang et al 2007 7Gaudernack et al 2006 7Yang et al 2006 7Yang et al 2006 7Uvnas-Moberg et al 1993 5Zheng et al 2013 8

further studies are expected for better understanding of effectof acupuncture in terms of gonadotropins

Although there were comparatively less studies whichexamined other sex hormones progesterone oxytocin hCGPrRP prolactin and GnRH hormone level was increased asa result of acupuncture Among the studies prolactin levelwas found to be increased by acupuncture In several otherstudies prolactin is increased as a result of acupuncturetreatment [39 40] It seems that acupuncture potentiallyincreases prolactin level yet more mechanism studies areneeded in order to verify exact effect of acupuncture on sexhormones

In terms of acupuncture method there was insuffi-cient number of correlation identified between acupunc-ture method and hormone changes For instance estrogenlevel was increased by use of MA in the study of Sunayet al [19] and there was also increased estrogen level inthe study of Wang et al [20] by using EA By contrastLH level was decreased in the study of Ma et al [17]However the studies included in this review not only havebroad range of acupuncture method but also have differentacupuncture forms (manual or electroacupuncture) dura-tions of treatment acupuncture points and intensities (seein Supplementary Table 1) Such diversity of acupuncturemethod made drawing definite conclusion hardly possibleThus further study is required to understand the relationshipbetween sex hormones and acupuncturemethodMeanwhileeffect of homeostasis regulating effect of acupuncture may

elucidatemechanism inhormone changes It was studied howacupoint specificity affects hypothalamic-pituitary-adrenalcortex axis (HPAA) regulation In addition it was suggestedthat acupuncture altered stress reaction neurons in par-aventricular nucleus [41] One of the key factors in brainactivity and homeostasis regulation Neuropeptide Y (NPY)which is highly concentrated in hypothalamus is involvedin the regulation of various physiological functions suchas energy homeostasis and stress-related behavior processSeveral studies investigated effect of acupuncture on crit-ical physiological processes In diabetic rats acupuncturesuppressed NPY and it led to controlling hyperphagia [42]Anxiogenic-like behaviors in maternally separated rats werealso recovered to normal state and decreased NPY expres-sion was upregulated by acupuncture [43] Acupunctureprevented elevation of NPY expression which was inducedby cold stress [44] The hormonal changes were inconsistentamong same disease modelsThe inconsistency is consideredto be due to different reasons of disease and used acupointsIt is suggested to focus more on the fact that acupuncturemay restore the balance among the hormones rather thansolely focusing on increase and decrease of hormone levelTo suggest clinical implications of acupuncture in variousdiseases it is important to recognize that acupuncture mayhave bidirectional effect depending on diseases It alsoshould be considered what physiological context a diseasepotentially has in order to properly account for effect ofacupuncture

Evidence-Based Complementary and Alternative Medicine 5

Table2Ch

angesinestro

genby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

ber

Disease

Acup

uncture

Acup

uncture

metho

dof

sample

(exp

con

)compa

redto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998771E2

998810E2

EAJohanssonetal

2013

Hum

anPC

OS

1114

998810E1E

1-SE

2EA

+MA

Feng

etal

2012

Animal(rat)

PCOS

4044

998771E2

EA+M

AMae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998810E2

998771E2

EAQin

etal

2013

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAYaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAZh

aoetal

2004

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998810E2

998771E2

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

≒Estro

gen

MA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒E2

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998810

E2998771E2

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998810

E2998771E2

EA

Zhangetal

2007

Animal(rat)

Pubertal

developm

ent

54

998810E2

998771E2

EA

998771Increased998810

decreased

and≒no

tsignificant

6 Evidence-Based Complementary and Alternative Medicine

Table3Ch

angesinFSHandLH

byacup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

Acup

uncture

metho

dCom

paredto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998810FSH998771

LH

998771FSH998810

LH

998810FSHLH

EA

Johanssonetal

2013

Hum

anPC

OS

1114

≒FSH≒

LH

≒FSHLH

EA+M

A

Feng

etal

2012

Animal(rat)

PCOS

88

≒LH

EA+M

A

Pasto

reetal

2011

Hum

anPC

OS

4044

≒FSHLH

998771FSHLH

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24≒FSHLH

998810FSHLH

EA

Zhengetal

2013

Hum

anPC

OS

43998810

FSH998810

LH

998810FSHLH

MA

Mae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998771LH

998810LH

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998771FSH998771

LH

≒FSH

(p=0053)

998810LH

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

998810FSH≒

LHMA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒FSH(p

=004

)≒LH

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998771FSH998771

LH998810

FSH998810

LH

998771FSHLH

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998771FSH998771

LH998810

FSH998810

LHEA

998771Increased998810

decreased

and≒no

tsignificant

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Quality assessment of studies included

Author Year Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 ScoreMaliqueo et al 2015 7Johansson et al 2013 8Feng et al 2012 7Pastore et al 2011 8Stener-Victorin et al 2000 7Ma et al 2017 8Qin et al 2013 8Yao et al 2007 7Zhao et al 2004 7Zhao et al 2003 7Sunay et al 2011 8Qu et al 2007 6Dong et al 2001 6Wang et al 2016 8Xiong et al 2015 8Zhou et al 2013 8Magarelli et al 2009 5Zhang et al 2007 7Gaudernack et al 2006 7Yang et al 2006 7Yang et al 2006 7Uvnas-Moberg et al 1993 5Zheng et al 2013 8

further studies are expected for better understanding of effectof acupuncture in terms of gonadotropins

Although there were comparatively less studies whichexamined other sex hormones progesterone oxytocin hCGPrRP prolactin and GnRH hormone level was increased asa result of acupuncture Among the studies prolactin levelwas found to be increased by acupuncture In several otherstudies prolactin is increased as a result of acupuncturetreatment [39 40] It seems that acupuncture potentiallyincreases prolactin level yet more mechanism studies areneeded in order to verify exact effect of acupuncture on sexhormones

In terms of acupuncture method there was insuffi-cient number of correlation identified between acupunc-ture method and hormone changes For instance estrogenlevel was increased by use of MA in the study of Sunayet al [19] and there was also increased estrogen level inthe study of Wang et al [20] by using EA By contrastLH level was decreased in the study of Ma et al [17]However the studies included in this review not only havebroad range of acupuncture method but also have differentacupuncture forms (manual or electroacupuncture) dura-tions of treatment acupuncture points and intensities (seein Supplementary Table 1) Such diversity of acupuncturemethod made drawing definite conclusion hardly possibleThus further study is required to understand the relationshipbetween sex hormones and acupuncturemethodMeanwhileeffect of homeostasis regulating effect of acupuncture may

elucidatemechanism inhormone changes It was studied howacupoint specificity affects hypothalamic-pituitary-adrenalcortex axis (HPAA) regulation In addition it was suggestedthat acupuncture altered stress reaction neurons in par-aventricular nucleus [41] One of the key factors in brainactivity and homeostasis regulation Neuropeptide Y (NPY)which is highly concentrated in hypothalamus is involvedin the regulation of various physiological functions suchas energy homeostasis and stress-related behavior processSeveral studies investigated effect of acupuncture on crit-ical physiological processes In diabetic rats acupuncturesuppressed NPY and it led to controlling hyperphagia [42]Anxiogenic-like behaviors in maternally separated rats werealso recovered to normal state and decreased NPY expres-sion was upregulated by acupuncture [43] Acupunctureprevented elevation of NPY expression which was inducedby cold stress [44] The hormonal changes were inconsistentamong same disease modelsThe inconsistency is consideredto be due to different reasons of disease and used acupointsIt is suggested to focus more on the fact that acupuncturemay restore the balance among the hormones rather thansolely focusing on increase and decrease of hormone levelTo suggest clinical implications of acupuncture in variousdiseases it is important to recognize that acupuncture mayhave bidirectional effect depending on diseases It alsoshould be considered what physiological context a diseasepotentially has in order to properly account for effect ofacupuncture

Evidence-Based Complementary and Alternative Medicine 5

Table2Ch

angesinestro

genby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

ber

Disease

Acup

uncture

Acup

uncture

metho

dof

sample

(exp

con

)compa

redto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998771E2

998810E2

EAJohanssonetal

2013

Hum

anPC

OS

1114

998810E1E

1-SE

2EA

+MA

Feng

etal

2012

Animal(rat)

PCOS

4044

998771E2

EA+M

AMae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998810E2

998771E2

EAQin

etal

2013

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAYaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAZh

aoetal

2004

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998810E2

998771E2

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

≒Estro

gen

MA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒E2

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998810

E2998771E2

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998810

E2998771E2

EA

Zhangetal

2007

Animal(rat)

Pubertal

developm

ent

54

998810E2

998771E2

EA

998771Increased998810

decreased

and≒no

tsignificant

6 Evidence-Based Complementary and Alternative Medicine

Table3Ch

angesinFSHandLH

byacup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

Acup

uncture

metho

dCom

paredto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998810FSH998771

LH

998771FSH998810

LH

998810FSHLH

EA

Johanssonetal

2013

Hum

anPC

OS

1114

≒FSH≒

LH

≒FSHLH

EA+M

A

Feng

etal

2012

Animal(rat)

PCOS

88

≒LH

EA+M

A

Pasto

reetal

2011

Hum

anPC

OS

4044

≒FSHLH

998771FSHLH

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24≒FSHLH

998810FSHLH

EA

Zhengetal

2013

Hum

anPC

OS

43998810

FSH998810

LH

998810FSHLH

MA

Mae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998771LH

998810LH

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998771FSH998771

LH

≒FSH

(p=0053)

998810LH

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

998810FSH≒

LHMA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒FSH(p

=004

)≒LH

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998771FSH998771

LH998810

FSH998810

LH

998771FSHLH

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998771FSH998771

LH998810

FSH998810

LHEA

998771Increased998810

decreased

and≒no

tsignificant

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

Evidence-Based Complementary and Alternative Medicine 5

Table2Ch

angesinestro

genby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

ber

Disease

Acup

uncture

Acup

uncture

metho

dof

sample

(exp

con

)compa

redto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998771E2

998810E2

EAJohanssonetal

2013

Hum

anPC

OS

1114

998810E1E

1-SE

2EA

+MA

Feng

etal

2012

Animal(rat)

PCOS

4044

998771E2

EA+M

AMae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998810E2

998771E2

EAQin

etal

2013

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAYaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998771E2

EAZh

aoetal

2004

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998771E2

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998810E2

998771E2

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

≒Estro

gen

MA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒E2

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998810

E2998771E2

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998810

E2998771E2

EA

Zhangetal

2007

Animal(rat)

Pubertal

developm

ent

54

998810E2

998771E2

EA

998771Increased998810

decreased

and≒no

tsignificant

6 Evidence-Based Complementary and Alternative Medicine

Table3Ch

angesinFSHandLH

byacup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

Acup

uncture

metho

dCom

paredto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998810FSH998771

LH

998771FSH998810

LH

998810FSHLH

EA

Johanssonetal

2013

Hum

anPC

OS

1114

≒FSH≒

LH

≒FSHLH

EA+M

A

Feng

etal

2012

Animal(rat)

PCOS

88

≒LH

EA+M

A

Pasto

reetal

2011

Hum

anPC

OS

4044

≒FSHLH

998771FSHLH

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24≒FSHLH

998810FSHLH

EA

Zhengetal

2013

Hum

anPC

OS

43998810

FSH998810

LH

998810FSHLH

MA

Mae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998771LH

998810LH

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998771FSH998771

LH

≒FSH

(p=0053)

998810LH

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

998810FSH≒

LHMA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒FSH(p

=004

)≒LH

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998771FSH998771

LH998810

FSH998810

LH

998771FSHLH

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998771FSH998771

LH998810

FSH998810

LHEA

998771Increased998810

decreased

and≒no

tsignificant

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

6 Evidence-Based Complementary and Alternative Medicine

Table3Ch

angesinFSHandLH

byacup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

Acup

uncture

metho

dCom

paredto

disease

Maliqueoetal

2015

Animal(rat)

PCOS

1012

998810FSH998771

LH

998771FSH998810

LH

998810FSHLH

EA

Johanssonetal

2013

Hum

anPC

OS

1114

≒FSH≒

LH

≒FSHLH

EA+M

A

Feng

etal

2012

Animal(rat)

PCOS

88

≒LH

EA+M

A

Pasto

reetal

2011

Hum

anPC

OS

4044

≒FSHLH

998771FSHLH

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24≒FSHLH

998810FSHLH

EA

Zhengetal

2013

Hum

anPC

OS

43998810

FSH998810

LH

998810FSHLH

MA

Mae

tal

2017

Animal(rat)

Ovarie

ctom

ized

88

998771LH

998810LH

EA

Sunaye

tal

2011

Hum

anMenop

ausal

synd

rome

2726

998771FSH998771

LH

≒FSH

(p=0053)

998810LH

MA

Quetal

2007

Hum

anMenop

ausal

synd

rome

3631

998810FSH≒

LHMA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11≒FSH(p

=004

)≒LH

MA

Wangetal

2016

Hum

anDim

inish

edovarianreserve

21998771FSH998771

LH998810

FSH998810

LH

998771FSHLH

EA

Zhou

etal

2013

Hum

anPrim

aryovarian

insufficiency

11998771FSH998771

LH998810

FSH998810

LHEA

998771Increased998810

decreased

and≒no

tsignificant

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

Evidence-Based Complementary and Alternative Medicine 7

Table4Ch

angesinotherh

ormon

esby

acup

uncturetreatment

Cha

nges

inho

rmon

elevel

Author

Year

Subject

Con

ditio

nNum

bero

fsam

ple

(exp

con

)Disease

Acup

uncture

compa

redto

Acup

uncture

metho

ddisease

Feng

etal

2012

Animal(rat)

PCOS

88

998810Progesterone

998771Progesterone

EA+M

APasto

reetal

2011

Hum

anPC

OS

4044

998771Testo

sterone

≒Testo

sterone

MA

Stener-Victorin

etal

2000

Hum

anPC

OS

24998810

Prolactin

998771Prolactin

EA

Yaoetal

2007

Animal(rat)

Ovarie

ctom

ized

88

998810PrRP

998771BrainPrRP

EAZh

aoetal

2003

Animal(rat)

Ovarie

ctom

ized

1012

998810GnR

H998771GnR

HEA

Don

getal

2001

Hum

anMenop

ausal

synd

rome

11998810

Progesterone

998810Prolactin

≒Progesterone

≒Prolactin

MA

Xion

getal

2015

Animal(rat)

Embryo

implantatio

ndysfu

nctio

n66

998810Progesterone

998810Prolactin

998771Progesterone

998771Prolactin

MA

Magarellietal

2009

Hum

anin

vitro

fertilizatio

n3433

998810hC

G

998810Prolactin

998771hC

G998771

Prolactin

NA

Gaudernacket

al

2006

Hum

anLabo

ur4852

NA

998810need

ofoxytocin

MA

Uvn

as-M

oberg

etal

1993

Animal(rat)

Normal

66

NA

998771oxytocin

EA

Yang

etal

2006

Animal(rat)

Analgesia

67

998810oxytocin

≒oxytocin

EAYang

etal

2006

Animal(rat)

Analgesia

99

998810oxytocin

≒oxytocin

EA998771Increased998810

decreased≒no

tsignificantandNA

not

applicable

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

8 Evidence-Based Complementary and Alternative Medicine

5 Conclusion

Our study has shown that acupuncture altered some of thesex hormone levels in both animal model and human It isdifficult to conclude that this reviewprovided strong evidenceto elucidate regulative effect of acupuncture on sex hormonesStill we believed that result of this review and holisticapproach to effect of acupuncture on sex hormones willcontribute to the field of hormonal study and acupuncturestudy as further guidance and reference

Data Availability

The data sets supporting the conclusions of this article areincluded within the article

Conflicts of Interest

The authors declare that they have no conflicts of interest

Authorsrsquo Contributions

JadeHeejae Ko and Seung-NamKim conceived and designedthis study extracted and analyzed the data and wrote thepaper All authors read and approved the final manuscript

Acknowledgments

This work was supported by the National Research Foun-dation of Korea funded by the Korean government (MSIT)(NRF-2017R1C1B5018061)

Supplementary Materials

Supplementary Table 1 Detailed description of acupuncturetreatment in the studies (Supplementary Materials)

References

[1] D Alpızar-Rodrıguez N Pluchino G Canny C Gabay and AFinckh ldquoThe role of female hormonal factors in the develop-ment of rheumatoid arthritisrdquo Rheumatology vol 56 no 8 pp1254ndash1263 2017

[2] S Berrih-Aknin R L Panse and N Dragin ldquoAIRE A missinglink to explain female susceptibility to autoimmune diseasesrdquoAnnals of the New York Academy of Sciences 2018

[3] S Saito K Suzuki K Yoshimoto et al ldquoA new bioassay formeasuring the strength of IL-6STAT3 signal inhibition bytocilizumab in patients with rheumatoid arthritisrdquo ArthritisResearch ampTherapy vol 19 no 1 2017

[4] S B Ahmed and S Ramesh ldquoSex hormones in women withkidney diseaserdquoNephrologyDialysis Transplantation vol 31 no11 pp 1787ndash1795 2016

[5] R Sharma K R Biedenharn J M Fedor and A AgarwalldquoLifestyle factors and reproductive health taking control of yourfertilityrdquo Reproductive Biology and Endocrinology vol 11 no 1p 66 2013

[6] C F HOLINKA ldquoHormonal Contraception Current Statusand Future Perspectivesrdquo Annals of the New York Academy ofSciences vol 734 no 1 pp 257ndash262 1994

[7] A Badawy and A Elnashar ldquoTreatment options for polycysticovary syndromerdquo International Journal of Womenrsquos Health vol3 no 1 pp 25ndash35 2011

[8] C L Westhoff S Heartwell S Edwards et al ldquoOral contracep-tive discontinuation do side effects matterrdquo American Journalof Obstetrics amp Gynecology vol 196 no 4 pp 412ndashe7 2007

[9] J-S Han and Y-S Ho ldquoGlobal trends and performances ofacupuncture researchrdquo Neuroscience amp Biobehavioral Reviewsvol 35 no 3 pp 680ndash687 2011

[10] S Cochrane C A Smith A Possamai-Inesedy and A Ben-soussan ldquoAcupuncture and womenrsquos health an overview of therole of acupuncture and its clinical management in womenrsquosreproductive healthrdquo International Journal of Womenrsquos Healthvol 6 no 1 pp 313ndash325 2014

[11] D M Upchurch L Chyu G A Greendale et al ldquoComplemen-tary and alternative medicine use among American womenfindings from the National Health Interview Survey 2002rdquoJournal of Womenrsquos Health vol 16 no 1 pp 102ndash113 2007

[12] A Burke D M Upchurch C Dye and L Chyu ldquoAcupunctureuse in the United States findings from the National HealthInterview Surveyrdquo The Journal of Alternative and Complemen-tary Medicine vol 12 no 7 pp 639ndash648 2006

[13] L Lu X G Zhang L L Zhong et al ldquoAcupuncture forneurogenesis in experimental ischemic stroke a systematicreview andmeta-analysisrdquo Scientific Reports vol 6 no 1 ArticleID 19521 2016

[14] M R Macleod T OrsquoCollins DW Howells and G A DonnanldquoPooling of animal experimental data reveals influence of studydesign andpublication biasrdquo Stroke vol 35 no 5 pp 1203ndash12082004

[15] J Johansson L Redman P P Veldhuis et al ldquoAcupunc-ture for ovulation induction in polycystic ovary syndrome arandomized controlled trialrdquo American Journal of Physiology-Endocrinology and Metabolism vol 304 no 9 pp E934ndashE9432013

[16] L M Pastore C D Williams J Jenkins and J T Patrie ldquoTrueand shamacupuncture produced similar frequency of ovulationand improved LH to FSH ratios in womenwith polycystic ovarysyndromerdquoThe Journal of Clinical EndocrinologyampMetabolismvol 96 no 10 pp 3143ndash3150 2011

[17] S Ma D Li J Jiang and B Shen ldquoRole of the medialpreoptic area in electroacupuncture treatment of reproductivedysfunction in ovariectomised ratsrdquo Acupuncture in Medicinevol 35 no 1 pp 52ndash58 2017

[18] Y Qin J He L Xia H Guo and C He ldquoEffects of electro-acupuncture on oestrogen levels body weight articular car-tilage histology and MMP-13 expression in ovariectomisedrabbitsrdquo Acupuncture in Medicine vol 31 no 2 pp 214ndash2212013

[19] D Sunay M Ozdiken H Arslan A Seven and Y Aral ldquoTheeffect of acupuncture on postmenopausal symptoms and repro-ductive hormones a shamcontrolled clinical trialrdquoAcupuncturein Medicine vol 29 no 1 pp 27ndash31 2011

[20] Y Wang Y Li R Chen X Cui J Yu and Z Liu ldquoElec-troacupuncture for reproductive hormone levels in patientswith diminished ovarian reserve A prospective observationalstudyrdquoAcupuncture inMedicine vol 34 no 5 pp 386ndash391 2016

[21] F Xiong J Gui W Yang J Li and G-Y Huang ldquoEffectsof acupuncture on progesterone and prolactin in rats of

Evidence-Based Complementary and Alternative Medicine 9

embryo implantation dysfunctionrdquo Chinese Journal of Integra-tive Medicine vol 21 no 1 pp 58ndash66 2015

[22] Kehua Zhou Jingxi Jiang Jiani Wu and Zhishun Liu ldquoElec-troacupuncture Modulates Reproductive Hormone Levels inPatients with Primary Ovarian Insufficiency Results from aProspective Observational Studyrdquo Evidence-Based Complemen-tary and Alternative Medicine vol 2013 Article ID 657234 7pages 2013

[23] Y-H Zheng X-H Wang M-H Lai H Yao H Liu and H-XMa ldquoEffectiveness of abdominal acupuncture for patients withobesity-type polycystic ovary syndrome A randomized con-trolled trialrdquo The Journal of Alternative and ComplementaryMedicine vol 19 no 9 pp 740ndash745 2013

[24] M Maliqueo A Benrick A Alvi et al ldquoCirculating gona-dotropins and ovarian adiponectin system are modulated byacupuncture independently of sex steroid or 120573-adrenergicaction in a female hyperandrogenic rat model of polycysticovary syndromerdquo Molecular and Cellular Endocrinology vol412 pp 159ndash169 2015

[25] Y Feng J Johansson R Shao L M Holm H Billig and EStener-Victorin ldquoElectrical and manual acupuncture stimula-tion affect oestrous cyclicity and neuroendocrine function in an5120572-dihydrotestosterone-induced rat polycystic ovary syndromemodelrdquo Experimental Physiology vol 97 no 5 pp 651ndash6622012

[26] E Stener-VictorinUWaldenstrom U Tagnfors T LundebergG Lindstedt and P O Janson ldquoEffects of electro-acupunctureon anovulation in women with polycystic ovary syndromerdquoActa Obstetricia et Gynecologica Scandinavica vol 79 no 3 pp180ndash188 2000

[27] X Yao X-QWang S-LMa and B-Y Chen ldquoElectroacupunc-ture stimulates the expression of prolactin-releasing peptide(PrRP) in the medulla oblongata of ovariectomized ratsrdquoNeuroscience Letters vol 411 no 3 pp 243ndash248 2007

[28] H Zhao Z Tian L Cheng and B Chen ldquoElectroacupunctureenhances extragonadal aromatization in ovariectomized ratsrdquoReproductive Biology and Endocrinology vol 2 article no 182004

[29] H Zhao Z-Z Tian and B-Y Chen ldquoAn important role ofcorticotropin-releasing hormone in electroacupuncture nor-malizing the subnormal function of hypothalamus-pituitary-ovary axis in ovariectomized ratsrdquoNeuroscience Letters vol 349no 1 pp 25ndash28 2003

[30] Z Zhaohui C Yugui Z Yuanming et al ldquoEffect of acupunctureon pubertal development of rats and rabbits at different devel-opmental stagesrdquoNeuropeptides vol 41 no 4 pp 249ndash261 2007

[31] L C Gaudernack S Forbord and E Hole ldquoAcupunctureadministered after spontaneous rupture of membranes at termsignificantly reduces the length of birth and use of oxytocin Arandomized controlled trialrdquo Acta Obstetricia et GynecologicaScandinavica vol 85 no 11 pp 1348ndash1353 2006

[32] J Yang W-Y Liu C-Y Song and B-C Lin ldquoThrough centralarginine vasopressin not oxytocin and endogenous opiatepeptides glutamate sodium induces hypothalamic paraven-tricular nucleus enhancing acupuncture analgesia in the ratrdquoNeuroscience Research vol 54 no 1 pp 49ndash56 2006

[33] J Yang W-Y Liu C-Y Song and B-C Lin ldquoOnly argininevasopressin not oxytocin and endogenous opiate peptides inhypothalamic paraventricular nucleus play a role in acupunc-ture analgesia in the ratrdquo Brain Research Bulletin vol 68 no 6pp 453ndash458 2006

[34] F Qu J Zhou and R Nan ldquoAcupuncture for PerimenopausalSymptoms in Women who Underwent Oophorectomy ndash aComparative Studyrdquo Complementary Medicine Research vol 14no 1 pp 25ndash32 2007

[35] H Dong F Ludicke I Comte A Campana P Graff and PBischof ldquoAn exploratory pilot study of acupuncture on thequality of life and reproductive hormone secretion in meno-pausal womenrdquo The Journal of Alternative and ComplementaryMedicine vol 7 no 6 pp 651ndash658 2001

[36] P C Magarelli D K Cridennda and M Cohen ldquoChanges inserum cortisol and prolactin associated with acupuncture dur-ing controlled ovarian hyperstimulation in women undergoingin vitro fertilization-embryo transfer treatmentrdquo Fertility andSterility vol 92 no 6 pp 1870ndash1879 2009

[37] K Uvnas-Moberg G Bruzelius P Alster and T LundebergldquoThe antinociceptive effect of non-noxious sensory stimulationis mediated partly through oxytocinergic mechanismsrdquo ActaPhysiologica Scandinavica vol 149 no 2 pp 199ndash204 1993

[38] K Patel M S Coffler M H Dahan P J Malcom R Deutschand R J Chang ldquoRelationship of GnRH-stimulated LH releaseto episodic LH secretion and baseline endocrine-metabolicmeasures in women with polycystic ovary syndromerdquo ClinicalEndocrinology vol 60 no 1 pp 67ndash74 2004

[39] Q W Xie and J Liu ldquoEffect of acupuncture on prolactinsecretion of lactating ratsrdquo Zhongguo Yi Xue Ke Xue Yuan YiXue Qing Bao Yan Jiu Suo Bian Ji vol 11 no 4 pp 303ndash3071986

[40] H G Kho J V Egmond C F Zhuang G L Zhang and GF Lin ldquoThe patterns of stress response in patients undergoingthyroid surgery under acupuncture anaesthesia in Chinardquo ActaAnaesthesiologica Scandinavica vol 34 no 7 pp 563ndash571 1990

[41] S Wang J Zhang H Yang FWang and S Li ldquoAcupoint speci-ficity on acupuncture regulation of hypothalamic- pituitary-adrenal cortex axis functionrdquo BMC Complementary and Alter-native Medicine vol 15 no 1 2015

[42] J Lee M Jang E Kim and C Kim ldquoAcupuncture decreasesneuropeptide Y expression in the hypothalamus of ratswith Streptozotocin-induced diabetesrdquo Acupuncture amp Electro-Therapeutics Research vol 29 no 1 pp 73ndash82 2004

[43] H-J Park Y Chae J Jang I Shim H Lee and S Lim ldquoTheeffect of acupunctureon anxiety and neuropeptide Y expressionin the basolateral amygdala of maternally separated ratsrdquoNeuroscience Letters vol 377 no 3 pp 179ndash184 2005

[44] L Eshkevari E Permaul and S E Mulroney ldquoAcupunctureblocks cold stress-induced increases in the hypothalamus-pituitary-adrenal axis in the ratrdquo Journal of Endocrinology vol217 no 1 pp 95ndash104 2013

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom