The Menstrual Cycle and Sport Performance

Title: The Menstrual Cycle and Sport Performance

Language: English

Authors: Naama W. Constantini, MD, DFM, Dip Sport Med, FACSMa, Gal Dubnov, MD, MScb, Constance M. Lebrun, MDCM, MPE, CCFP, Dip Sport Med, FACSMc

Date: 2005

This

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ClinSportsMed24(2005)e51–e82

Femaleathletes,coaches,medicalprofessionals,andresearchershavelong beenfascinatedwithpotentialmenstrualcyclefluctuationsinathleticperformance,secondarytothedifferentialeffectsofsexsteroidhormones.Studieshave shownthatestrogencaninfluencethecardiovascularsystem(includingblood pressure,heartrateandrhythm,andvascularflow),substratemetabolism,and eventhebrainitself.Progesteroneandotherprogestins,ontheotherhand,appear tomainlyaffectthermoregulation,ventilation,and,toalesserextent,thechoice andusageoffuelforenergyneeds.Theendresultscanbeadditiveorsynergistic, interactiveorevenantagonistic.Changingrelativeproportionsofhormones throughouta‘‘regular’’ovulatorymenstrualcyclecanpotentiallyaltermany

Thefemalereproductivelifecycleisoneofthemostimportantbiological rhythms.Fromprepubertythroughtomenarche,conception,pregnancy,the postpartumperiod,menopause,andbeyond,thefemaleathleteisexposedtoa constantlyshiftingkaleidoscopeofendogenoussexsteroidhormones.Although estrogenandprogesteronearethemostimportantintermsoftheiractionson thevariousbodysystems,morerecentresearchhasexploredtheeffectsofother hormones,suchastestosterone,relaxin,andleptin,tonamejustafew.Oral contraceptivesandhormonereplacementtherapyfurtherintroduceexogenous synthetichormones(invaryingproportions)totheequation.

NaamaW.Constantini,MD,DFM,DipSportMed,FACSMa,*, GalDubnov,MD,MScb,ConstanceM.Lebrun,MDCM, MPE,CCFP,DipSportMed,FACSMc

aDepartmentofPhysiology,Tel-AvivUniversity-SacklerFacultyofMedicine,4HaarazimStreet, Tel-Aviv,Israel

bDepartmentofHumanNutritionandMetabolism,HebrewUniversity–HadassahMedicalSchool, Jerusalem,Israel

0278-5919/05/$–seefrontmatter D 2005ElsevierInc.Allrightsreserved. doi:10.1016/j.csm.2005.01.003 sportsmed.theclinics.com

cFowlerKennedySportMedicineClinic,UniversityofWesternOntario,London,Ontario, CanadaN6A3K7

TheMenstrualCycleandSportPerformance

*Correspondingauthor. E-mailaddress: naamacon@tapuz.co.il(N.W.Constantini).

Mood Arousal Cognition Cardiovascular Heartrateandrhythm Strokevolume Bloodpressure Bodyfluidvolume Coagulation Vascularfunction Sympatheticactivity Respiratory Ventilation Asthma Metabolic Corebodytemperature Thermoregulation

Restingoxygenconsumption

importantfacetsofathleticperformance,itselfacomplexphenomenon.Componentsofsportsperformancethatmaybeaffectedbythemenstrualrhythm arelistedin Box1.Menstrualcyclevariationinaerobicandanaerobiccapacity, aerobicendurance,andmusclestrengthhasbeeninvestigatedtosomeextent. Maximalphysicalperformancerequiresanarrayofmentalandphysicalfunctions actinginoptimalconcert.Thefemalehormonescanaffectmanyofthesefactors; hencethecyclingofestrogenandprogesteronelevelscaninfluenceperformance inmanyways.Therelativelycommonoccurrenceinathletesofmenstrualdys-

Box1.Componentsofsportsperformancethatmaybeaffectedby themenstrualrhythm

Brainfunction

Substrateavailabilityandmetabolism Acid-basebalance Strength Aerobiccapacity(VO2 max) Anaerobiccapacity Responsetoergogenicaids Glucose Caffeine Orthopedic Injuryrate Ligamentlaxity Lowbackpain constantini e52etal

Properstudydesignandmethodologyarenecessaryforanymeaningful researchintotherelationshipbetweenthemenstrualcycleandathleticperfor-

Themenstrualcycle

Themenstrualcycleisperhapsthesecondmostimportantbiologicalrhythm, nexttothecircadianone.Itiscreatedbytheinterplaybetweenhypothalamic, hypophyseal,andovarianhormones,bringingaboutvariouschangesnotonlyin thefemalereproductivetractbutalsoinmanyothertissuesofthebody.Itis traditionallydividedintotwophases(follicularandluteal)orthreephases (follicular,ovulatory,andluteal),basedonovarianfunction.Thefollicularphase beginsonthefirstdayofmenses,lastsanaverageof9days,andistheperiod whenfolliclesaregrownundertheinfluenceofthehypophysealfolliclestimulatinghormone(FSH).Estrogenlevels,secretedfromthecellssurrounding thisfollicle,slowlyincrease,inducingthesecretionofthehypophyseal luteinizinghormone(LH).Asestrogenlevelsincreasefurther,asurgeofLHis secreted,andabout1daylaterovulationoccurs.Thismarksthebeginningofthe ovulatoryphase,whichlastsabout5days.Duringthesephases,endometrial thicknessincreasesinpreparationforreceivingtheembryo.Afewdaysafterthe folliclehasreleasedtheovum,itistransformedintotheprogesterone-secreting corpusluteum,bringingaboutthelutealphase,whichnormallylasts14days. Progesteroneactstosupporttheendometriumuntiltheembryocancreatethe placenta,whichwilltakeoverthisfunction.Attheendofthelutealphase, progesteronesecretionfromthecorpusluteumceases,theendometriumisno longersupportedanditsloughsoffasmenstrualbleeding.Asestrogenlevels decreaseinthesedays,FSHsecretionenhancesandbeginsthecycleagain.The threephasesofthecyclearethereforedifferentiatedfromoneanotherbythe estrogenandprogesteronelevelratios:(1)lowestrogenandlowprogesterone levelsarepresentduringthefollicularphase,(2)highestrogenandlow progesteronelevelsarepresentduringtheovulatoryphase,and(3)highestrogen andhighprogesteronelevelsarepresentduringthelutealphase.

Methodologicalconsiderations

function(suchasamenorrhea,oligomenorrhea,anovulation,andshortluteal phase)furthercomplicatesthepicture.Thisdysfunctionmaybemoreprevalentin certainsportsparticularlyattheelitelevel,whichiscoincidentallymadeupof athleteswhohavethegreatestvestedinterestinperformanceenhancement. Unfortunately,mostpreviouslypublishedresearchislimitedbymethodological problems,preventingundisputedconclusions.Previousreviewshavedescribed earlierstudiesindetail [1–3],sothisarticleprimarilyfocusesonmorecontemporarywork.

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Anotherconfoundingfactoristhepossibletimelagbetweenchangesinhormonelevelsandanyimpactonperformance.Forexample,onestudyemploying hormonelevelmeasurementonadailybasisfounda4-daytime-phasedelay betweenthehormonalchangesandtheireffectonkneelaxitychanges [6].The hypothesisthatsimilartime-shiftsexistwithothercomponentsofperformance stillneedstobeexamined.

Otherfactors,suchasthetimeofdayor‘‘ultradianrhythm’’ [4],ambient temperatureandhumidity,nutritionandhydration,fitnesslevel,andtraining statusmustalsobestandardizedinanyexercisestudy.

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Allstudiesrequireadequatedocumentationofmenstrualcyclephase,as naturalvariabilityincycle-phaselengthprecludessimplenumberingofthedays ofthecycle.Numerousreferencemethodsareusedtomonitorovulationand, byextension,menstrualcyclephase [5].Calendarcalculation,measuringthe increaseinbasalbodytemperature(BBT)afterovulation,andexaminingchanges incervicalappearanceanditsmucusaresimpleandinexpensivemethods,butare inaccurate.Definitivedeterminationoffollicular,ovulatory,andlutealphasesof themenstrualcyclerequirestheassessmentofserumestradiolandprogesterone levels.Concentrationsofthesehormonesinthesalivaorurineappeartocorrelate withserumlevels,andthereforecollectionofthesefluidsmaybeusedasnoninvasivemethods.However,usingurinesamplestodetectthemidcycleLHsurge canbelessaccurate.

mance.Casereportsorclinicalseries(withorwithouthistoricalcontrols)and cross-sectionalstudiesdonotoffermuchhelpfulinformationandcannotbe generalizedforalargerpopulation.Case-control(retrospective)studiesare notoriouslypronetosubjectiverecallandothertypesofbias.Prospectiveand historicalcohortscanbefollowedforafewcycles,butonlyrandomizedclinical trialsprovidethebestevidenceofalterationsinathleticperformanceattributable toeitherendogenousorexogenoushormonalvariations.Manytechnicalissues arisewhenattemptingtoconstructaconsensusregardingmenstrualcycleand exerciseperformance.Theseincludecyclephasedefinitionsandverification, timingofhormonemeasurements,exercisetesting,andinjurydocumentationand theirassociations [4]

Twodifferentapproachesareusedtodividethemenstrualcycle.Asomewhat olderonecomparesthepremenstrualandmenstrualdayswiththerestofthe cycle.Thesedaysconsistofpsychologicandphysicaldiscomfort,fluidretention, headaches,bloating,breasttendernessand,ofcourse,bleeding.Thesefactors mayeasilycombinetoreduceperformance.Thesecondapproachdividesthe cyclebyhormonelevels,intotwo(follicular/lutealphases),three(follicular/ ovarian/lutealphases),orfive(earlyfollicular/latefollicular/ovarian/earlyluteal/ latelutealphases)stages.Comparisonofstudiesusingthesemethodsisdifficult, asthepremenstrualandmenstrualdaysspanlutealandfollicularphases,each withverydifferenthormonelevels.Also,manyfemaleathletes(depending ontheirsportandotherriskfactors)mayhavelutealphasedeficiencyor anovulation.Therefore,estimationofcyclephasewithoutmeasuringhormone levelsmaybeinappropriate.

Finally,itisimportanttodistinguishbetweenstatisticallysignificantandbiologicallyorfunctionallysignificantdifferences,asmostracesoreventsarenot wonbyastatisticallysignificantmargin.

Estrogeninitsvariousformsisresponsibleforthedevelopmentofsecondary sexualcharacteristicsandthetypicalfemalepatternoffatdepositioninthe breasts,buttocks,andthighs.Progesteronecan,inmanyways,haveantiestrogenicandandrogenicactions.Circulatingestrogenandprogesteronelevelscause variationinmanycardiovascular,respiratory,andmetabolicparameters,with subsequentimplicationsforstrengthandaerobicandanaerobicperformance. Muchlessisknownabouttheeffectsofthevariousandrogensinfemaleathletes, whichwerefoundtobeelevatedinsomeathleteswithmenstrualdysfunction [7,8].Theprogestinscurrentlyusedinoralcontraceptives(andinjectableforms ofbirthcontrol)havevaryingestrogenic,progestogenic,andandrogenicactions. Manyotherhormones,suchasgrowthhormoneandcortisol,arealsoimpacted, whichfurtherconfusestheunderstandingofexperimentalfindings.

Cardiovascularsystem

Thereisalsoathehighvariabilityamongsubjects,whichcanimpede conclusionsfrombeingdrawnfromstudiesinvolvingasmallnumberofsubjects orwhenapplyingstudyresultstoasingleathlete.

Biologicaleffectsofthesexsteroidhormones

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Cardiovascularresponsestostress(eg,myocardialischemia)aremoreeasily elicitedwhenestrogenconcentrationsarelow(ie,duringthefollicularphase); conversely,inwomenwithpremenopausalcoronaryarterydisease,thebest treadmillperformanceoccurredatmidcycleorovulation(ie,phasescharacterized byhighblood-estrogenlevels) [12].ArecentDopplerechocardiographicstudyof leftventricularstructureandfunctionduringthemidfollicularandmidluteal phasesdidnotdocumentanysignificantdifferences,butthetimeofmaximal estrogenconcentration(ie,immediatelybeforeovulation)wasnotcaptured [13]

Therelationshipbetweenthefemalereproductivehormonesandthecardiovascularsystemiscomplexandrelatedtomyriadsitesandmechanismsofaction [9].Someissuesrelevanttosportperformancearethatestrogencanenhance endothelium-dependentvasodilatation [10],andtherealsoappearstobea differenceincardiacexcitabilitypossiblycausedbycalciumantagonismor inhibitionofangiotensin-convertingenzyme.Estrogenandprogestinstimulatetherenin–angiotensinsystem,asuggestedmechanismofend-lutealphase (ie,premenstrual)fluidretention.Administrationofexogenousformsofthese hormonesfoundinoralcontraceptivesorhormonereplacementtherapy(HRT) mayhavesimilarconsequences.Otherhormones(suchasvasopressinand corticotropin)thatinfluencefluidbalanceandvasculartonealsoappeartobe affectedbymenstrualcyclephase [11].

Thesexsteroidhormonesareinvolvedinthecentralneuralcontrolof breathing,affectingcentralneurotransmitters,peripheralchemoreceptors,and perhapsthelungandairways [15,16].Endogenousprogesteroneleadstoagreater minuteventilationandmaximalexerciseresponseduringthelutealphaseofthe menstrualcycleandduringpregnancy,whereassyntheticmedroxyprogesterone acetatecaninducesimilarrespiratoryresponsesinmalesubjectsandin postmenopausalwomen.Estradiolincreasesthenumberandsensitivityof progesteronereceptors,socombinationhormonaltherapycouldtheoretically haveanevengreaterinfluence.Inaddition,theoverallsensitivityoftherespiratorydriveappearstobeenhancedbyaloweringofthethresholdandan increaseinexcitabilityofthemedullaryrespiratorycenter.Thisactioncanpotentiallybedetrimentaltoendurance-trainedathletes,whonormallybenefitfrom decreasedhypoxicandhypercapneicrespiratorydrivesatrestandduring exercise.However,thishasonlybeensignificantinuntrainedathletes [17]

Premenstrualandperimenstrualaggravationofasthma(asmeasuredbypeak expiratoryflowrate)canbeseeninupto30%to40%ofasthmaticwomen,even thoughtheymaynotbeawareofit.Cyclicallyincreasedvisitstoemergency departmentsforasthmahavebeendocumented [20].Moststudies,however,have beenperformedinnonathleticpopulationswithouthormonalverificationofcycle phase.Theclinicalpossibilitiesarenumerous.Forexample,thelatelutealphase dropinplasmalevelsofprogesterone(aknownsmoothmusclerelaxant)might leadtobronchoconstrictionthroughwithdrawalofitseffectonbronchialsmooth muscle.Inaddition,estradiolisassociatedwithincreasesinacetylcholine concentration,mucussecretion,andprostaglandinproduction.Furthermore, ventilationatrestiscontrolledbycentralandperipheralchemoreceptors,whereas

Progesteronemayincreasecardiacexcitabilitybyitsopposingeffectsonestrogen.Increasedcardiovascularstrain(ie,higherheartrate)hasbeendocumentedforthesamelevelofworkduringthelutealasinthefollicularphase [14], buttheassociatedluteal-phaseincreaseinbodymassandbodytemperature makesitdifficulttointerpretthisinformation.

Increasedventilationleadstoapartiallycompensatedrespiratoryalkalosis, buttheconcurrentleftshiftinthepHcurvecausedbyincreasedtemperature duringthelutealphasemaymeannonetconsequencesintermsofoxygen deliveryfromtheredbloodcellstothetissues [18].Nocorrelationhasbeen foundbetweenventilationandprogesteronelevels,butthismightbecausedbya time-phasedelayintheeffectofthehormone,circulatinglevelsofbound progesterone,orinteractionwithotherhormonessuchasestradiol.Otherreproductivehormones(eg,LH,FSH,prolactin),catecholamines(eg,epinephrine,norepinephrine),thyroidandadrenocorticalhormones,dopamine,leptin,and serotonin,justtonameafew,alsoappeartobeinvolvedinthecomplexcontrol ofbreathing.Environmentalfactors,suchasexposuretohighaltitude,alsohave additionalpotentialtoalterventilationduringthemenstrualcycle [19]

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Respirationandventilation

Fig.1.Relationshipofskinbloodflowandinternaltemperature,dependingoncyclestateorthe presenceofestrogen.(From CharkoudianN,JohnsonJM.Femalereproductivehormonesandthermoregulatorycontrolofskinbloodflow.ExercSportSciRev2000;28(3):108–12;withpermission.)

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Thermoregulation

Progesteroneandthesyntheticprogestinshaveacentralthermogeniceffect, modulatedatthelevelofthepreoptic/anteriorhypothalamus.Thisisresponsible fortheincreaseinBBT(0.38Cto0.58C)duringpregnancyandthelutealphaseof thecycle,andthesmallercoretemperaturechangesseenwithoralandinjectable formsofcontraception.Alteredskinbloodflow [24] andanincreasedthreshold forcutaneousvasodilatationandonsetofsweatingarethoughttobethemajor mechanismsofthisaction,aspresentedin Fig.1

neurogenicfactorspredominateduringexercise.Andlastly,acetylsalicylicacid andothernonsteroidalanti-inflammatorydrugs(NSAIDs),frequentlytakenfor dysmenorrhea,mayaffectairwayresistancethroughprostaglandininhibition [21].Inthesubgroupoffemaleasthmaticswhohavemenstrual-linkedasthmaor perimenstrualasthma,theremaybeafuturerolefor‘‘respiratoryendocrinology’’ andhormonalmanipulationwithmedicationssuchasprogesteroneordanazol, oralcontraceptives,orGnRHagonistsandanalogs.Currentknowledgeregarding asthmaandthesexhormonesiswellreviewedinrecentpublications [22,23],but thereisanobviousneedforfurtherwell-designedstudiesofsufficientsample sizetobuildevidenceinthisarea.

Ahighercorebodytemperaturemayreducethesafemarginforheataccumulationwhenexercisingorevenworkinginahotenvironment,decreasingthe timetofatigue [25].Duringthelutealphase,andespeciallyunderconditionsof extremeheatandhumidity,femaleathletesmaybeatathermoregulatory disadvantagefortrainingandcompeting [26,27].Theremayalsobeindirectand

Theknowngenderdifferencesinenergymetabolismarelargelycausedbythe differentialactionsofthesexsteroidhormones [29].Researchinanimals [30] andhumanshasshownthatestrogenpromotesglycogenuptakeandstoragein liverandmusclethroughincreasedlipidsynthesisandenhancedlipolysisin muscle.Higherlevelsofestrogen(andprogesteronetoalesserextent)tendto spareglycogenstoresbyshiftingmetabolismmoretowardfreefattyacids [31]. Thismetabolichormonalactionmaycontributetowomen’senhancedcapability forultra-enduranceexercise,ascomparedwithmen.Thisgreaterdependenceon fatstoresforenergyisprimarilyseenatcertain(lowtomoderate)exercise intensities,whereasgreaterrelativeeffortsdependincreasinglyonbloodglucose andmuscleglycogenassubstrates [32].

independenteffectsfromthehigherheartrateandgreatersenseofexertionduring thisphase.Interestingly,thermo-sensitivitytocold-waterimmersiondoesnot seemtobeaffectedbymenstrualcyclephase [28].

Substratemetabolism

Overall,progesteronelikelyalsoshiftssubstratemetabolismtowardagreater dependenceonfat,throughantagonismofthelipolyticeffectsofestrogen,but accentuationofitscarbohydrate-sparingeffects(constraintofperipheralbloodglucoseuptake,decreasedhepaticglycogenolysis).Thereisdebateastowhich hormonehasthepredominantfunctionandatwhichtimeinthemenstrualcycle thisismostmanifest:aroundthetimeofovulation,implyingthatitisprimarily anestrogeneffect [33],orduringthelutealphasewhenbothhormonesarehigh (andmusclebiopsieshavedocumentedhighermuscleglycogenstores) [34] Changingabsoluteandrelativeproportionsofestradiolandprogesteronemakeit extremelydifficulttoascertaintheindividualhormonaleffectsinhumanstudies. Additionally,theovarianhormonesmayhaveindirecteffectsonsubstratemetabolismthroughinteractionswithotherhormones,suchasthecatecholamines, especiallyduringexercise [35].Endocrineandintracellularfactorsplaycritical rolesindeterminingsubstratebalanceduringsustainedexercise.However,glucoseingestioncanimproveperformanceregardlessofmenstrualphase(Fig.2).

Estrogenisbelievedtoimprovecarbohydratetolerancethroughactionson lipolyticenzymesandglucoregulatoryhormonessuchasgrowthhormone, catecholamines,andinsulin,aneffectoppositetothatofprogestins.Arecent review [36] describesthecomplexinteractionsofthesehormonesandenergy metabolism.Deteriorationofcarbohydratemetabolismandrelativeglucose intoleranceduringthelutealphasehasalsobeenattributedtoprogesterone, throughitscontra-insulineffectsonextrahepatictissuesandincreaseininsulin resistance.Inrats,progesteronedecreasesglucosetransporterprotein(GLUT-4) contentinskeletalmuscleandadiposetissue.Inhumans,theinsulinresistanceof pregnancyisatleastpartiallycausedbytheactionsofprogesterone,andmayalso contributetotheonsetofgestationaldiabetesmellitus.Thesyntheticprogestins thatarecurrentlyusedinoralcontraceptiveshavevaryingeffects,dependingon theirandrogenicity,withnorgestrelandlevonorgestrelbeingthemostpotentin

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thisregard,andnorethindronehavingtheleastimpact.Thereareobviousclinical implicationsforthechoiceofmedicationsinpatientswhohavediabetesmellitus orglucoseintolerance.Inthispopulation,theremayalsobeminorvariationsin glucosecontrolduringanovulatorymenstrualcycleorpostmenopause,butthere aremanyotherconfoundingvariablestofactorin.Asmusclecontractionisafar morepotentstimulusforglucoseuptakethaninsulin,exercisestudiesatdifferent menstrualcyclephasesareneededtolookattheeffectoffemalesexsteroidson glucoseuptakeduringexercise.

Fig.2.Timetocompleteacycleergometertestduringfollicularandlutealphases,withorwithout carbohydrateingestion.Notebetterperformanceinthefollicularphasecomparedwiththelutealphase ( P b .05),andthatperformancewithglucoseingestionwassimilarinbothphases.CHO, carbohydrate.(From CampbellSE,AngusDJ,FebbraioMA.Glucosekineticsandexercise performanceduringphasesofthemenstrualcycle:effectofglucoseingestion.AmJPhysiol EndocrinolMetab2001;281:E817–25;withpermission.)

Inthebehavioralliterature,thereissomeevidencethatestrogenmaypotentiallymediatedifferentaspectsofcognition,alertness,andcognitiveperformance [37].Beneficialeffectsoncognitivefunctionandverbalmemoryarebelievedto besecondarytochangesintheavailabilityofneurotransmitterssuchasserotonin inthebrain.Estrogenandtestosteronehavedemonstratedoppositeinfluenceson modulationofspatialcognition [38],whereasprogesteronemayhavenegative, evensedative,effects [39].Higherlevelsofestradiolduringthelutealphase arepostulatedtocausepoorerperformanceontasksofspatialability [40,41]. However,fewearlystudiesoncognitivefunctionsandthemenstrualcycleuse anythingmorethancalendarestimationofcyclephase,somostarelittlemore thanconjecture.Morerecently,advancedimagingtechniques,suchasfunctional MRIstudies,inconjunctionwithmeasurementofsexsteroidhormonelevelsare beingusedtobetterdelineateneuropsychologicparametersassociatedwith menstrualcyclephasesandHRT.Althoughthisfieldisstillinitsinfancy,its

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Psychologicalfactors:estrogenandthebrain

potentialimportanceshouldnotbeignored,becauseatleastsomeofthesemental functionsarerequiredincertainsportingactivities.

Themenstrualcycleandphysicalperformance

Someinvestigatorshavereportedaninotropiceffectofestrogenonmuscle [43],peakingjustbeforeovulation,ofa10%to11%magnitude [44],andpostulatedaswitchingofmusclecross-bridgesfromlow-tohigh-forcegeneration. Therewasanassociatedslowingofrelaxationandincreaseinfatigabilityat midcycle,butbecauseofthelackofhormonalverificationofcyclephasethese findingsaresomewhatsuspect.However,anotherstudythatdidmonitorLH, estradiol,andprogesteronelevelsconcludedthatmaximalvoluntarymuscle contractionwassignificantlyhigherintheovulatoryphase,perhapsrelatedto intrinsiccontractileproperties [45].Acontemporarystudyeliminatedmanyof themethodologicalproblemsfoundinthepreviousliterature [46] byusing electricalstimulationtoensuremaximalneuralactivationandmusclecontraction. Inthisstudy,theinvestigatorsfoundnosignificantchangesinquadricepsmuscle strength,fatigability,orelectricallystimulatedcontractilepropertiesin19women overthreephasesofthemenstrualcycle,andnosignificantcorrelationsofanyof thestrengthindiceswithfemalereproductivehormoneconcentrations.

Muscularstrength(eg,handgripstrength,isokineticandisotonickneeflexion andextension,legandbenchpress)doesnotappeartofluctuatesignificantly duringanovulatorymenstrualcycle.Althoughmorerecentstudiescontain hormonaldocumentationofcyclephase [14,42],thenumbersarestillsmall. Inadditiontotheathleticarena,therecanbeimportantimplicationsforthe workplaceandindustry.Onestudylookedatmanualhandlingperformance (eg,isometricand10-minutedynamicliftingperformance)atfivedistincttimes inthecycle:menses,midfollicular,ovulation,midluteal,andpremenses(72hours beforemenses) [42].Neithermaximalisometricliftingstrength(MILS)nor endurancetimeat45%ofMILSattwostandardizedheightswereaffectedby menstrualcyclephase.Alutealphaseincreaseintheheartrateresponseto exercise(of7beats/min)suggestedincreasedcardiovascularstrain,possiblyrelatedtoeitheralterationsinbloodfloworthermoregulation.

Severalfactorsrelatedtothemenstrualcycle,includingpsychologicand physical,affectathleticperformance.Keyphysicalfactorsarestrength,and aerobicandanaerobiccapacity.

Mostrecently,researchersstudiedtenmoderatelyactivesubjectsovertwo consecutivemenstrualcyclesduringhormonallyverifiedtimes:earlyfollicular phase,ovulation,andmidlutealphase.Testsincludedhandgripstrength,one-leg hoptest,isokineticmusclestrength,andmuscleendurance [47].Thisstronger

Menstrualcycleandstrength

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Menstrualcycleandaerobiccapacity

Forthemostpart,itdoesnotappearasifmaximaloxygencapacityand submaximalexerciseresponsesaresignificantlydifferentduringanyphaseofthe menstrualcycle.Previousstudieshavebeenreviewedindetailelsewhere [1,2,4] Someresponsesdosuggestapossibleslightdecrementinaerobiccapacity [48] or exerciseefficiencyduringthelutealphase [55].Thisdecrementcanbeseenin Fig.2,alongwithanincreaseinoxygenconsumptionandmetabolicrate. Runningeconomy(therateofoxygenconsumptionduringagivensubmaximal steady-staterunningspeed)hasbeenexaminedatfivehormonallydistincttimes inthecycle,withconcomitanthormonalverification.Alowerrunningeconomy wasfoundat80%,butnot55%,ofmaximalaerobiccapacityduringtheluteal phase,withassociatedchangesinventilatorydrivesandfluctuationsinmood state [56].Ventilatorychangesmaybemoresignificantunderconditionsof diminishedoxygenavailability.Inarelativelylargegroupofsedentaryhighaltitudenativewomenexercisingat3600m,maximalworkoutputwasapproximately5%higherduringthelutealphase,withhighersubmaximalminute ventilationandventilatoryequivalents,butnooveralleffectonVO2max [57].A separatestudyoflowlanders,usingahypobaricchambertosimulatealtitude,did notdocumentanysignificantdifferencesineitherventilationorphysicalperformance [19].Thecorollaryofsuchfindingsforathletestrainingandcompeting atsealevelisunclear.Anothergrouptestedeightmoderatelyactivewomen duringthreeseparatehormonallyverifiedcyclephases:earlyfollicular(low estrogenandprogesterone),midfollicular(elevatedestrogenandlowprogesterone),andmidluteal(elevatedestrogenandprogesterone [58].Nosignificant differencesinlactatethreshold,VO2max,oranyothermeasuresofcardiorespiratoryfitnessweredetected.Menstrualcycleeffectsonvariousaspectsof athleticperformancelikelyvarygreatlybetweenindividuals,makingitessential foreachwomantomonitorherownresponseanddocumentthetimesatwhich shetrainsandperformsherbest.

repeated-measuresdesignconfirmedtheearlierandmorecurrentresearchresults [48,49] showingalackofsystematicmenstrualcyclevariationinstrength parameters.Otherstudiescontinuetoreportacircamensaleffect,possiblycaused byperipheralratherthancentralmechanisms [50].Somehaveevensuggested periodizationoftrainingprogramsforfemaleathletestotakeadvantageofany optimalhormonalfluctuations [51].Thisconceptisnotsofar-fetched,as estradiol,inadditiontoexerciseitself,isknowntomodifygrowthhormone(GH) secretionandmetabolism [52].Theanaboliceffectsofthishormonemay promotemaximalmusclegainatcertaintimesduringthenaturalmenstrual cycleorhormonallycontrolledcyclesinwomentakingoralcontraceptives [53]. Similarly,aseparatebodyofliteratureisemergingonthepotentialclinicaluseof estrogenreplacementtherapyinpostmenopausalwomentopreservemuscle strength [54].

Aftervigoroussustainedexercise,thereisanecessaryrepaymentofoxygen debt,whichcanbequantifiedasexcesspostexerciseoxygenconsumption (EPOC).TheEPOCandrestingmetabolicratehavebeenshowntobesignificantlyhigherandthepostexerciserespiratoryexchangeratio(RER)(anindirect measureoffatoxidation)significantlylowerduringthelutealphasecompared withthefollicularphase,suggestinggreateruseoffatforfuel [62].Incontrast, otherinvestigatorshavereportednomenstrualcyclephasechangesintheeffects ofcarbohydratesupplementationonperformanceorinplasmalevelsofrelated substratesduringprolongedexerciseat70%VO2max [63].Itislikelythatbaselinenutritionalstatusandglycogenstoresandadequatecarbohydratereplenishmentduringexercisecontributeasmuchormoretoenhancementofperformance thanmenstrualcyclephase,asseenin Fig.2[55].

Nevertheless,subtledifferenceshavebeennotedinbloodglucoseresponsesto moderateandshort-termhigh-intensityexerciseacrossmenstrualcyclephase. Theseappeartoberelativelyresilienttodiurnalrhythmsofcortisol [64].Withthe developmentofisotopictracersofglucoseandglycerolhascometheabilityto monitorsubstrateturnoverduringexerciseinmoreaccuratedetailduring exercise,usingthedualcathetertechnique.Althoughsuchstudiesshouldhelpto clarifypreviousconflictingresults,theyactuallyaddtotheconfusion.Somehave measuredalowerglucosefluxduringexerciseinthemidlutealversusearly follicularphasesatintensitiesof90%oflactatethreshold(LT),butnotat70%LT [65].Anotherinvestigationofwomenexercising50%ofVO2peakataltitudedid notfindanysignificantdifferences [66].Otherstudieshaveshownnoalteration inwhole-bodyexercisenutrientoxidation(protein,fat,andcarbohydrate)in responsetomoderate-intensitylong-durationexercisebetweenearlyfollicular,

Althoughthecombinedeffectsofthefemalesexsteroidhormonesonsubstratemetabolismcouldtheoreticallyaffectaerobicendurance,evidencetodateis contradictory.Animprovementhasbeenreportedduringthelutealphase,in associationwithincreasedmuscleglycogen [33,34] ordiminishedbloodlactate (thebalanceoflactateproducedbyworkingmuscles,againstwhatisclearedor metabolized) [59].Themagnitudeofsuchchangemaybegreaterwithan adequateantecedentdietthanwiththehormonesalone.Forexample,an8% greaterlutealphaseenduranceandmuscleglycogenstoragewasdemonstratedon ahigh-carbohydratedietcomparedwithamoderate-carbohydratediet [60].A widevarietyofdifferentprotocolshavebeenused,includingincrementalversus steady-stateexercise,differingpercentagesofaerobiccapacity,andcycle ergometerversustreadmilltesting.Standardizationofothervariables,suchas thetimeofday,nutritionalstatus,orpsychologicalmotivationofthesubjects,has beeninconsistent.Theimpactofmenstrualcyclephaseandoralcontraceptiveuse (withtheadditionofthermalstress)hasbeenstudiedwithmorecomplicated protocols,suchasintermittenthigh-intensityshuttlerunninginahotenvironment [61].Ascanbeimagined,theamountofdatageneratedinsuchstudiesisstaggering,andinterpretationoftheresultscanbeconfusing.

Menstrualcycleandaerobicendurance

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Manybelievethattheseeffectsonglucosekineticsarelargelycausedby estradiol,andhaveattemptedtostudythishormoneinisolation.Administration oftransdermalestrogentoamenorrheicwomendecreasedglucosefluxatrestand duringmoderateintensityexercise,butdidnotcauseanysignificantchangein therelativecontributionofglucoseandglycogentototalbodycarbohydrateuse [68].Thepostulatedmechanismsincludeddecreasedgluconeogenesis,epinephrinesecretion,orglucosetransport.Similarly,whenmenweregivenahigher relativedoseofestrogenintheformoforalestradiol,theydemonstrateddecreasedglucosefluxwithoutanyeffectonsubstrateoxidationduringexercise [69].However,theunderlyinghormonalmilieuinthesetwosubjectpopulations isnotrepresentativeofthechangesthattakeplaceoverthecourseofanovulatory menstrualcycle,whereestrogenandprogesteronelikelyinteracttoaffectexercise glucosemetabolism.Recently,someexcellentworkinonelaboratoryconfirmed nosignificantmenstrualphaseeffectonglucoseflux,andtheinvestigators attemptedtoputitallinperspective:

latefollicular(highestradiol),andlutealphases [67].Neitherwereoverallplasma glucosekineticssignificantlyalteredacrossthesecyclephases,despiteagreater increaseinglucoseandinsulinconcentrationsduringexerciseinthelutealphase. Theseinvestigatorscorrectlypointoutthatsomeofthediscrepanciesfromearlier workcouldhaveresultedfromgroupingearlyfollicular(lowhormone)and latefollicular(ie,timeofovulation)phasestogether.Inaddition,themethod ofchoosinganddeterminingexerciseintensitydiffersbetweenstudies.For example,insomeitisrelativetothesubject’sVO2max,inothersapercentageof LT.Workinthisareaisfurthercomplicatedbythetrainingstatusofthesubjects, inthatthemorephysicallyfitwomenmayhavedifferentpatternsofglucoseuse and,byextension,demandsonendogenousglucose.

Becauseofthecomplexityofthesediversehormonalinteractions,itis stronglysuggestedthatvariationsinsexsteroidsbecontrolledforinmetabolic studiesusingfemalesubjects.

Theresultsareinterpretedtomeanthatinwomenfedseveralhoursbeforethe study,1)glucosefluxisdirectlyrelatedtoexerciseintensity,2)menstrualcycle phasedoesnotalterglucosefluxduringrestandexerciseand3)thesubtle effectsofendogenousovarianhormonesonglucosekineticsaresubordinateto themuchlargereffectsofexerciseandrecentcarbohydratenutrition [70].

Menstrualcycleandanaerobiccapacity

Anaerobiccapacityreflectsrapiduseofthephosphagen(creatinephosphate) andATPstoresinthelocalmuscles,withtypeIIfibersprovidingthelargest contribution.Anaerobicenduranceoranaerobicglycolysiscanbeestimatedusing numerouslaboratoryandfieldtests.Intheanaerobicspeedtest,subjectsdoa maximaltimedruntofatigueonatreadmillataspeedof8mphanda20%grade [48].Anaerobiccapacityalsoinvolvesmeasuressuchasmeanpoweroutput andpeakpoweroutput.Arecentstudyofseveneumenorrheicwomenduring

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Themenstrualcycleandperformanceindifferentsports

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menstruation,midfollicularphase,andmidlutealphases,andtenwomentaking monophasicoralcontraceptives,examinedforce-velocity(maximalcyclingpower onacycleergometer),multi-jump(maximaljumppower),andsquattingjump tests(maximaljumpheight) [71].Therewerenosignificantdifferencesbetween phasesorintheoralcontraceptivegroupinanymeasureofanaerobic performance.However,itwassuggestedthatthepresenceorabsenceofpremenstrualormenstrualsyndromesymptomsmighthaveaneffect,possibly throughthestretch-shorteningcycleoftendonsandligaments.Otherstudieshave foundeithernodifferenceinanaerobicpoweroutputbetweencyclephases,or greateranaerobiccapacityandpeakpowerduringthelutealphase [72,73].Newer excitingtechnologies,suchasnuclearmagneticresonancespectroscopy,makeit possibletoinstantaneouslyandobjectivelyassessmusclephosphatedynamicsat thecellularlevel.Suchtechniqueswillofferafascinatingwindowintomuscle metabolismduringthemenstrualcycle.

Fewstudieshaveintentionallyaddressedmenstrualcycleandperformancein specificsports.Brooks-Gunnetal [74] testedswimmingtimesofadolescent swimmersovera12-weekperiod.Theyfoundthatswimmingwasfastestduring menstruationandslowestduringthepremenstrualperiod.However,therewere onlysixsubjectsinthisstudy,menstrualcyclewasassessedbyBBTchanges,and onlyhalfoftheswimmershadaclearbiphasictemperature.

Peakathleticperformanceiscomposedofanatomic,physiologic,metabolic, biomechanical,andpsychologicelements.Therelativecontributionofeachof theseelementsvaries,dependingonthetypeofsport.Therefore,thediverse effectsonperformancewillnotnecessarilyresultinanysignificantchangesin actualachievements.Theventilatoryeffectsofhormonesmaybemorerelevant toanaerobicsport,asthermoregulationmaybemorerelevantonahotday; hormonelevelsononedaymaynotbethesameonthenext;acurrentcyclemay beanovulatory;andexternalfactors,evenanargumentwithaboyfriendorcoach, mayinteractwiththepsychologicinfluenceofonespecificcyclephase,butnot another.Therefore,itisnotsurprisingthatmostoftheearlyliteratureonathletic performancewasbasedonsubjectivefeelingsalone,disregardingspecificmenstrualcyclephase [74].Dataareinconsistent;manyathletesinthesestudies reportedadecreaseinperformanceduringthepremenstrualandmenstrualphase, whereasothersreportedperformanceenhancementduringtheirmenstrualphase, winninggoldmedalsandbreakingworldrecords.InarecentstudyfromGreece [75],overhalfof373athletesfromsixdifferentdisciplinescomplainedof abdominal/thoracolumbardiscomfort,fatigue,ornervousnessduringmenstruation,yetovertwothirdsofthesubjectsdidnotfeelthesecomplaintsimpacted theirperformance.Goldmedalshavebeenwonthroughoutthefemalecycle, emphasizingthatmenstrualphaseeffectsarenotsodramatic.

Insummary,fewstudieshaveexaminedtheendresultofmenstrualcycle influenceonperformanceintheactualsporttype.Additionalstudiesusing athletesfromdifferentsportdisciplinesareneededtohelpanswerthequestionof whetherthemenstrualcyclesignificantlyimpactsonperformance.Negative resultsmaysuggestthat,ingeneral,menstrualcyclephaseshouldnotbeconsideredamajordeterminant.However,datashouldstillbecollectedtoassist thoseindividualathleteswhofeel(orareproventobe)detrimentallyaffectedbya certaincyclephase.

Womenhaveahigherinjuryrateinsportsthanmen,sometimesbyafactorof almostten [78].Thesedatahavebeenaccumulatedfromactivitiessuchasball games,running,andmilitarytraining.Suggestedmechanismsthatmaybe affectedbythefemalehormonesincludeanatomicandbiomechanicalfactors, neuromuscularcontrol,andligamentlaxity.Interestingly,femalesalsohave higherinjuryratesinsporttypesthatdonotincludethemorecommonrunning, jumping,andlandingactivities.Inarecentstudyonmountainbikinginjuries, womenexhibitedalmosttwicetheinjuryratecomparedwithmen [79].The investigatorspostulatedthatlowerbodyandbonemassmayincreasetherisksof fallsandfractures.Still,moststudiesfocusonkneeinjuriesandthelaxityofthe anteriorcruciateligament(ACL).

Menstrualcycle,injuries,andligamentlaxity

Onestudyofcrosscountryskiersfoundthatperformancewasbetterinthe earlylutealandlatefollicularphases [76].Again,cyclephasewasdeterminedby BBTwiththeadditionofcervicalmucusexamination.Astudyconductedamong 16femalerunners(onlyeightwereeumenorrheic)foundnoeffectofcyclephase onaerobicparametersorperceivedexertion [77].Here,cyclephasewasdeterminedbyplasmaandurinehormonelevels.

Inthepast4decades,severalstudieshavereportedontheincidenceofACL injuryrelatedtothemenstrualcyclephase [80–84],withthemorerecentones usingmeasurementsofhormonelevelsratherthanrelyingsolelyonself-report. Wojtysandcolleagues [85] describedaclusteringofinjuriesintheovulatory phase(ie,days10through14)ofthemenstrualcycle.Alower-than-expectedrate ofeventsoccurredinthelutealphase.Menstrualcyclewasdeterminedby questionnaireandurinaryhormonelevels,butonlyfairagreementwasfound betweenthetwomethods.Hence,oneshouldusecautionregardingstudiesusing self-report,asverificationofthephaseofabiologicalrhythmcanbedifficult.In anotherstudy,twothirdsofACLinjuriesweresustainedduringthefollicular phase,withasmallclusteralsofoundwithinthefirst2daysofmenses [83].Here, menstrualcyclephasewasdeterminedbyquestionnaire,andsalivaandplasma hormonelevels,withagoodcorrelationreportedbetweenthesemethods.

ThesestudiessuggestapotentiallyhigherincidenceofACLinjuryduring theovulatoryphase,andaloweroneduringthelutealphase.Itisunclearwhether thefollicularphaseharborsincreasedrisk.Additionalstudieshavebeen

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Theanteriorcruciateligament

IthasbeenfoundthatPMSaffectsinjuryriskinsomewomencomparedwith thosewhodonotexperiencesymptoms [84].Inastudyexaminingbalanceand kinesthesiaasrelatedtothemenstrualcycle,itwasfoundthatwomenwhohad PMShadpoorerbalanceandmotionperceptioncomparedwithwomenwhodid nothavesymptoms [47].Asplasmahormonelevels(eg,FSH,LH,estrogen, progesterone)didnotdifferbetweengroups,anothermechanismmayexplain thesefindings,suchasotherhormonesorpsychologicfactorsthatwere notmeasured.

Muchattentionisalsodirectedtowardcellulareffectsoffemalehormoneson ACLlaxity,whichisacontroversialissue.Althoughseveralstudiesdoshow increasedACLlaxityinthelutealphase,othersdonot.Heitzetal [89] measured ACLlaxityamong11femalesubjectswhileassessingcyclephasebyplasma levels.Increasedlaxitywasseeninthelutealphase,comparedwiththefollicular. Deieetal [90] measuredACLlaxityevery3to4daysamong20females,along withplasmahormones.Largerkneelaxitywasobservedintheovulatoryand lutealphases,comparedwiththefollicularphase.Shultzetal [6] usedmuch morecomplexmethods,measuringkneelaxityandplasmalevelsofestrogen, progesterone,andtestosteroneonadailybasis.Kneelaxityincreaseswere associatedwithhigherlevelsofestrogen,progesterone,testosterone,andallthree hormonestogether.Increasesinkneelaxitythatwereassociatedwithallthree hormonesmaybeseeninthelutealphase.Atimelagof3to4dayswasfound betweenhormonelevelchangesandlaxitychanges.Otherstudies,however, didnotfindanassociationbetweenmenstrualcyclephaseandkneelaxity. Karageanesetal [91] measuredkneelaxityin26adolescentfemaleswhilecycle phasewasdeterminedbyself-report.Nostatisticallysignificantdifferencewas foundinACLlaxitybetweenthephasesofthemenstrualcycle.Belangeretal [92] measuredkneelaxitybeforeandafterexercisealongthreephasesofthe cyclein18athletes.CyclephasewasdeterminedbyBBTandmenstruation reports.ACLlaxitywasnotaffectedbyeitherexerciseormenstrualcyclephase.

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performedusingquestionnairesamongprofessionalathleteswhichhaveyielded conflictingresults,perhapsasaresultofmethodologicalissuesdiscussedearlier.

Injurymechanism

ThereareseveralsuggestedmechanismsforthehigherrateofACLinjury infemales,althoughtheneuromuscularfactorseemstobethemostimportant [86,87].Asestrogen,progesterone,andrelaxinmayaffectneuromuscularfunction,changesinhormonelevelsthroughoutthemenstrualcyclecanbeacausefor injurydispersionalongthecycle.Musclestrengthhasbeenfoundtoincrease aroundthetimeofovulation,butsohasmuscularfatigability,apossiblereason forincreasedinjuryrateatthistime [88].Asmentionedearlier,thisissueis notundebated.

[85] Urinehormones X z A Slauterbeck,etal [83] Salivahormones za z A Kneelaxity infollicularphase Kneelaxityin ovulatoryphase Kneelaxityin lutealphase

[93] PlasmahormonesReferencevalue XX

A

VanLunenetal [93] usedanarthrometerandplainfilmsamong12females, measuringACLlaxityattheearlyfollicular,ovulatory,andmidlutealphases, asassessedbyhormonelevelsinplasmaandurine.Nostatisticallysignificant changeinACLlaxitywasfound,asdeterminedbyeitherthearthrometerorthe radiographstudies.

Study Methodofcycle assessment Injuryratein follicularphase Injuryratein ovulatoryphase Injuryratein lutealphase

[6] PlasmahormonesReferencevalue zz z

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Thereasonsfortheapparentdiscrepanciesamongthesestudiesare,asalways, methodological.Studiesdifferedinthesubjectpopulation(athletesornonathletes),theexactperiodofthemenstrualcycleexamined,themethodofcycle verification,themethodoflaxityassessment,andtheappliedforces.Therefore, ameta-analysisisnecessarytocombinethedatafromthesestudiesanddraw appropriateconclusions.

Hence,itisunclearwhethertheincreaseinkneeinjuriesisrelatedtochanges inhormonelevels. Table1 presentsstudiesusinghormonalverificationofmenTable1

Effectofmenstrualcycleoninjuryrateandanteriorcruciateligamentlaxityinstudiesusinghormonal verificationofcyclephase

Wojtys,etal

[89] PlasmahormonesReferencevalue zz

Heinz,etal Deie,etal [90] VanLunen,etal Shultz,etal ,increase; ,decrease; ,nochange. Especiallyondays1to2ofmenses.

PlasmahormonesReferencevalue zz

X

Themechanismofthepossiblechangeinlaxitythroughoutthecyclemay includeadirectactionofestrogenontheligament.Estrogenreceptorsexistin humanACL [94],andaninhibitoryeffectofestrogenonfibroblastproliferation andcollagenproductioninhumanACLhasbeendemonstrated [95].Progesteronewasfoundtobeprotectiveinthismatter,whichmaypartiallyexplainthe reducedinjuryrateobservedinthelutealphaseofthemenstrualcycle.Other potentialhormonesaffectingligamentlaxityarerelaxin,estrone,andtestosterone.Onestudyfoundnoeffectofrelaxinonkneelaxityamongfemaleathletes [96].Inanotherstudy,estronewasfoundtocorrelatenegativelywithligament laxity [97].Testosteronelevelsalsochangeoverthemenstrualcycle,butthishas onlybeenrarelyaddressedinstudiesonkneelaxity,despitethefactthat testosteronehasbeenfoundtohaveanevengreatereffectthanprogesterone [6]. Futurestudiesontheeffectsofhormonesortheircombinationsonligament laxityareneeded.

a

Therapeuticconsiderations

Injuryprevention

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strualcyclephasesoninjuryrateandACLlaxity.Itseemsthatalthoughthere isanincreaseininjuryrateduringtheovulatoryphaseandadecreaseduringthe lutealphase,kneelaxityincreasesduringboth.Itisuncertainwhethera relationshipbetweenthesesmallchangesinlaxityandinjuryratesexists.Does increasedlaxityleadtoincreasedinjury(thekneemay‘‘give’’more),asmaybe seenintheovulatoryphase,orisitprotective(alaxligamentmaytearless easily),asseeninthelutealphase?Additionalmechanismsmustthereforeplaya roleinkneeinjuries.

Thequestionof how toalterthemenstrualcycletoimproveperformance mustonlybeaskedfollowingthequestion whether themenstrualcycleshouldbe altered.Mostoftheliteratureindicatesthatregularlymenstruatingfemaleathletes donotneedtoadjusttheirmenstrualcycletomaximizeperformance,unless possiblycompetinginenduranceeventsunderhotandhumidconditions.Also,

Mostresearchersraisethequestionofwhetheroralcontraceptivepill(OCP) useaffectsinjuryratedistributionalongthevariousstagesofthemenstrual cycle [82–85],yetsamplesizeshavebeentoosmallfordetailedstatistical comparisonswithnonusers.Moller-NielsenandHammar [84] didfinda decreasedriskfortraumaticlowerextremityinjuriesinthepremenstrualand menstrualperiodsamongOCP-usingsoccerplayers,yetseveralmethodological considerations,suchasthesmallernumberofathletesusingOCPsortheirolder age,remainpossibleconfounders.Arecentstudyfounddecreasedkneelaxity amongOCPuserscomparedwithnonusers [98].However,theinclusionof monophasicandtriphasicpillsinthesamegroup,thedisregardingofmenstrual cyclephaseinbothgroups,andthecross-sectionaldesignprohibitany conclusionregardinghormonaleffects.Inherreview,Ireland [86] reportsona consensusconferenceheldin1999,stressingthatthereisnojustificationforsexspecifichormonalmanipulationtopreventACLinjuries.Onemorerecentstudy hasshownthatapreventiontrainingprogramconsistingofrunning,jumping,and balanceexercisesenabledsomereductionininjuryrateamongfemalehandball players [99].Hewett [87] designedanothertrainingprogram,andtheAmerican AcademyofOrthopaedicSurgeons [100] alsopublishedanofficialguidefor ACLinjuryprevention.Suchprogramsareextremelyimportant,regardlessof menstruationeffects.ThepreventionofACLinjuriesandoptimaltreatmentare critical,andtheirimportancefurtherunderscoredbythehighincidenceof osteoarthritisandfunctionallimitationsfoundasmuchas12yearsafteracute ACLinjuryamongfemalesoccerplayers [101].

Inearlieryears,afairnumberofwomen,includingOlympicathletes,didnot trainduringtheirmenses;apracticewhichfortunatelyisnolongercommon.

Over100differentsomaticandpsychologicqualitiesandchangeshavebeen describedaspartofPMS.Thoughsymptomsareminorinmostcases,theymay sometimespreventtheathletefromreachingherfullcapability.Inaddition,the increasedinjuryrateandpoorerbalanceandmotionperceptionoccurringin womenwhohavePMSmayevenposearisk [47,84].Tothoseathleteswho areseverelyaffected,shiftingthetimeofPMSawayfromacompetitionor prohibitingmenses(thuspreventingPMS)bycontinuousOCPusemayprove helpful.Additionaltherapeuticoptionsincludepsychologicinterventions,dietary modifications(eg,saltrestriction,increasedcarbohydrateintake),orpharma-

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Education

thepatternofthehormonalchangesduringthemenstrualcycleandanyphysiologicandpsychologiceffectsdiffergreatlyfromonewomantoanother.Therefore,evenifthereisaconsensusonaparticulareffect,thateffectdoesnot necessarilyapplytotheindividualathlete.

Athletesandcoachesshouldreceiveinformationaboutthepathophysiologyof thenormalmenstrualcycleanditsrelationshiptophysicalactivityand performance.Theyshouldunderstandthatdespitepossibleminorphysiologic disadvantagesinsomeareasofperformance,apositivepsychologicattitudecan behelpful.Worldrecordshavebeenbrokenduringmenstruation,andOlympic goldmedalshavebeenwonthroughoutthecycle.

Theattitudetowardthemenstrualcycleingeneral,anditsnegativeeffecton performanceinparticular,isofteninfluencedbysocialandculturalbeliefs,which mayresultinself-fulfillingprophecies [104].

Premenstrualsyndrome

Still,althoughpremenstrualandmenstrualsymptomsarelessfrequentand severeinathletes,theycanbedisablingandshouldbetreatediftheyinterfere withtrainingandcompetition.OCPs,otherthanbeingareliablecontraception method,haveseveraladditionalbenefits.Forone,theycanpostponemensesuntil afteracompetitionor,alternatively,inducemensesbeforeit.Theycanalso reducePMS,dysmenorrhea,menorrhagia,anddysfunctionaluterinebleeding, therebydecreasingtheriskofirondeficiencysoprevalentinfemaleathletes [102,103].And,notexclusivetoathletes,theycanreducefunctionalovarian cysts,benignbreastlesions,andendometrialandovariancancers,and,ofcourse, preventunwantedpregnancies.Whatevertheintention,thistypeofintervention shouldbelimitedtoonlymature,eliteathletes,whoseperformanceis undoubtedlyaffectedbytheirmenstrualcycle,anditshouldbeusedonlyfor criticalcompetitionsandnotfortrainingorminorevents.

Dysmenorrheaaffects47%to80%ofthegeneralpopulation [105].Inathletes, theincidenceandseverityisdecreasedasaresultoflowerprostaglandinsor higherpainthreshold.Inmostofthecasesthesymptoms,whichincludelower abdominalpainoftenradiatingtothelowerbackorlegs;headache;nausea;and vomiting,aremild.Becausethepainiscausedbyincreasedprostaglandinsecretionfromtheendometrium,NSAIDsareveryeffectiveinreducingsymptoms. Treatmentiseffectiveifinstitutedatthesignoffirstbleedingandusuallyrequires 2to3days.OCPusealsotendstoreducesymptomsofdysmenorrhea.

cologicmeasures(eg,pyridoxine50to150mg/d,spironolactone100mg/d,or progesterone50to400mg/d).

Trainingprogram

IntheformerSovietUnion,coachesusedtoplanthetrainingsessionsaccordingtothemenstrualcycle [106].Theytheorizedthatthemenstrualcycle couldbedividedintofivestages,andthathigh-intensityloadingshouldbe doneonlypostovulationandpostmenstruation.Becauseofweightchangesand physicalandpsychologicstress,trainingshouldbelighterduringovulation, premenstruation,andmenstruation.Eachathletekeptalogofhermensesandthe lengthofeachstage,andtrainedaccordingly.Thisideaofindividualizationofthe trainingroutinemakessense,especiallyattheelitelevel;however,thevarious stageswerenotsupportedbyhormonemeasurements.Thereiscurrently noscientificexplanationorsupportfortheconceptofavoidinghigh-intensity trainingduringmostofthemenstrualcycle.

Progesterone

Dysmenorrhea

Anathletewhohasaregularmenstrualcycleandwhocannotordoesnotwant totakeHRTorOCPsbutwantstoavoidmenstruationduringthetimeofcompetitioncantake10mgofhydroxylprogesteroneforfiveconsecutivedaysfrom day15ofthecycle.Withdrawalbleedingwillthenoccurwithinabout2days, thusadvancingthemenstrualcyclebyaweek.

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Hormonalmodificationofthemenstrualcycle

Themenstrualcyclecanbeeasilycontrolledandmanipulatedbyhormonal therapies.However,therapeuticusageofhormonesmerelyformenstrualmanipulationshouldbesavedonlyformature,eliteathleteswhoseperformance isnegativelyaffected,asthehealthimplicationsofcontinuousshiftingofthe menstrualcyclearenotyetknown.

Oralcontraceptivepills

Estrogen&progesterone

Oralcontraceptivepillsandperformance

Athleteswhoarenotsexuallyactiveandwhodesireshiftinginthetimingof theirmenstrualcyclecantakeacombinationofestrogenandprogesterone,such asKliogestorActivelle(NovoNordisk,Denmark).Theamountofestrogenin thesetabletsisminimal(2mgand1mgestradiol,respectively),whichlessens thechanceofweightgainorbreastdiscomfort.

Todate,therearenostudiesconcerningtheeffectofthesehormones onperformance.

AlthoughtheOCPhasbeentoutedas‘‘arevolutionforsportswomen’’ [107], concernstillremainsaboutanypotentialdetrimentaleffectonperformance. Monophasiccombinationpillsconsistofanestrogenicandprogestogeniccomponentinfixeddoses,whereasbiphasicandtriphasicpreparationsattemptto morecloselymimictheconditionsofanaturalmenstrualcyclebyvaryingthe hormonalconcentrations.Progestin-only‘‘minipills’’andinjectableorimplantableformsofprogesteronearealsoeffectiveforcontraception.Morerecently, amonthlyinjectablecombinationofestradiolandprogesteronewasdeveloped. Earlierpillscontainedmuchhigherhormonalconcentrationsthancontemporary formulations.Lowerestrogenlevels(30 mgand20 mgofethinylestradiol,comparedwiththeinitialdosesof150 mg)andmoreselectiveprogestogenicagents (eg,gestodene,desogestrel)havelargelybeensuccessfulindecreasingunwanted sideeffectsand,morethanlikely,anyputativeassociatedeffectsonathletic performance.Giventhewidespreadusageofthesemedications,studiesaresurprisinglyscarceinthisarea.

Somestudieshavesuggestedapotentialdeclineinaerobicperformance (VO2max)inresponsetooralcontraceptiveadministration,rangingfrom5%to 11%butreversibleondiscontinuationoftherapy [2,3].Morerecentpublications haveshownaslightdecreaseinmaximalaerobiccapacity [108,109] orno

Anincreasingnumberofathletesattherecreationalandelitelevelsuseoral contraceptivesforcyclecontrolorcontraceptivepurposes.Inaddition,these medicationsareusedformanagementofpremenstrualsymptoms,dysmenorrhea, andtime-shiftingofthemenstrualcycle.Therapeutically,physiciansfrequently prescribethemforwomenwhohaveprolongedmenstrualdysfunction,suchas amenorrheaandoligomenorrhea.OCPsmayhavepotentialosteogenicactions, andperhapsalsoprovideprotectionagainststressfracturesandothersofttissue injuries,butthecurrentevidenceissomewhatcontradictory [107].Otherpossible benefitsincludeprotectiveeffectsagainstheartdiseasethroughactionsonendothelialfunctionandlipoproteins,amongothers.

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Ithasalsobeensuggestedthatreductionofpremenstrualsymptoms,such asfatigue,fluidretention,weightgain,anddysmenorrhea,mayalsoimprove athleticperformance.Decreasedmonthlybloodlossandalowerincidenceofiron deficiencyanemiaarelikelybeneficialtoenduranceathletes.

Finally,potentialalterationsinbodycompositionwithOCPadministration havebeenconsidered.Thelargestandmostcomprehensivestudytodate compared26enduranceathletes(13whoexperiencedregularmenstruationand 13whoexperiencedoligo/amenorrhea)with12sedentarycontrolsbeforeand after10monthsoftreatmentwithalow-dose,combinedmonophasicOCPcon-

Dependingonthecombinationofhormonesused,therearetheoreticalbenefits forcardiacoutput(increasedvascularvolumeandpreload).Theremayalso beeffectsontheperipheralcirculationthroughtheactivityofnitricoxide [113]; however,itisdifficulttodissociatecardiovascularfunctionsfromthermoregulatoryeffects.Dependinglargelyontheprogestincomponent,thebiphasicbody temperatureresponsefoundineumenorrheicwomenissomewhatattenuatedin OCPusers [114].Thishasvariouslybeenfoundtocauseahigherheartrateand reducedcapacity [115,116] ortomarginallyimproveperformancecompared withthepill-freedays [61].Themagnitudeofanythermoregulatoryeffect likelydependsonthetypeofprogestinandestrogeniccomponentsofOCPsand theirinteraction.

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Strengthmaybeimpactedbyadirectactionofestradiolonmusclecrossbridges,orindirectlythroughstimulationofGHsecretion.Possibleandrogenic actionsoftheprogestinsinOCPshave,inthepast,alsobeenthoughttoimprove musclestrength,andOCPscontainingnorethindronewereevenbannedbythe InternationalOlympicCommitteeforawhile.Inarecentstudyontheeffectof 10monthsofOCPtherapyonperformanceoffemaleathletes [120],nochangein isometricmeasurements(kneeextensionandhandgrip)wasdemonstrated.

IntermsofOCPsandsubstratemetabolism,somehavesuggestedatrend towardcarbohydratesparing,withashifttowardfreefattyacidsforfuel [117].A lowerbloodglucoseresponseduringexercisecouldresultfromadecreasein hepaticglucoseoutputorenhancedglucoseuptakeinmuscles,orcouldbe causedbyalterationofglucoregulatoryhormonesandinsulinsensitivity [118,119].However,OCPscancauseinsulinresistance,risesinplasmainsulin, andrelativeglucoseintolerance [117].Itisdifficulttodrawmeaningfulconclusionswhenmoststudypopulationsconsistoflessthantenwomentaking multipleOCPs.Muchmoreresearchisneeded,andsubstrateturnoverstudies wouldalsobehelpfulinthisarea.

significanteffects [110],despiteincreasesinbloodlactateandammoniaresponsestohigh-intensityintermittentexercise [111].Astudyoffiveeliterowers takingatriphasicOCPfoundaloweranaerobicpowerandanaerobiccapacity duringthetimeofhighestexogenoushormoneadministration [112].Another group [71] founda3%to5.8%loweroxygenconsumptionforagivenexercise intensity,andimprovedrunningeconomyonamonophasicOCP.Generalization ofanyofthesefindingsislimitedbythesmallsubjectnumbersandthewide rangeoftestingprotocolsandoralcontraceptiveformulationsused.

taining30 mgethinylestradiol [120].Althoughlittleimpactonenduranceperformancewasseen,therewasaminimaldecreaseinperformanceonamultistage progressiveshuttle-runtest,the‘‘beeptest,’’intheoligo/amenorrheicathletes only,associatedwithanincreaseinfatmass.Morecomprehensivestudiesare necessarytofurtherdelineateanyproposedeffectofOCPsonbodyfatinathletes,especiallygiventhelowerhormonalconcentrationsincontemporaryOCPs.

Thosewhodonotmindcompetingwhiletakinghormonescancontinueto takemonophasicpillsuntilafterthecompetitions.Thepillscanbetakenfora coupleofmonthswithnoriskotherthanbreakthroughbleeding(ie,spotting) [121].Recently,a3-monthpillcontaining30 mgethinylestradioland150 mg levonorgestrel(Seasonale,DuraMedPharmaceuticals,Inc.,NewYork)wasintroduced.Thisextended-cycleOCPiseffective,safe,andwell-toleratedand allowswomentheoptionofdecreasingthenumberofwithdrawalbleeding intervalsfrom13to4peryear [122].Extendedregimensofupto126daysof OCPscontaining30 mgethinylestradioland3mgdrospirenonehavealsobeen showntoofferpositiveeffectsthatmightbeparticularlyadvantageoustothe athlete,suchasadecreaseinweightgain,breasttenderness,bloating,andsome psychologicsymptoms [123].Otherpreparationshavealsobeenusedincyclesof 2to3monthsandmore,significantlyreducingthenumberofmenstrualperiods peryear.Thisreductionisparticularlyadvantageousforthefemaleathlete,asit

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ThereisanextensivechoiceofOCPs,manywithvarioustypesandamounts ofestrogenandprogesterone.WhichOCPtoprescribeisanindividualdecision anddependsonwhatthespecificneedsofthewomanareandwhatsuitsher.The estrogencomponentisusuallyethinylestradiol,andadoseof20to30 mgis usuallywell-tolerated.Theprogesteronesvaryintermsofpharmacologic properties.Somehaveantiandrogenicorantimineralocorticoidactivity,which canofferfavorableeffectsintermsofskin,hair,andwaterretention.

Withacarefulyearlyplanning,itispossibletoshortenthecycleoverafew monthsbydecreasingthenumberofpillsineachcyclesothatthemajorcompetitionwilloccurwhendesired(usuallyathletesprefertocompeteafterbleeding hasceased,whenlevelsofestrogenandprogesteroneareattheirlowest).Another optionistostoptheOCPs10daysbeforetheanticipatedcompetition;bleeding usuallyoccurswithin2daysandlastsfor5to7days.

Prescribingoralcontraceptivepillsformenstrualcyclemanipulation

Themonophasicpills,inwhichthedoseofbothhormonesisconstant throughoutthecycle,areeasiesttouseduringcompetitionandtravel.Biphasic andtriphasicpills,althoughbetterintermsofmimickingthenaturalcycle,are hardertomanipulate.

Intheabsenceofmedicalcontraindications,suchasthromboembolicdisease, impairedliverfunction,andestrogen-dependentneoplasia,OCPscanbeprescribedtoathleteswhoareatleast2yearspostmenarche,asadministrationatan earlieragemighthaltgrowth.

Reductionof PMS

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Bonelossprevention(associatedwitholigomenorrhea andamenorrhea)

PossibleDisadvantages

Cramps

Breasttenderness

Decreaseinpeakexercisecapacity(VO2max)

Ectopicpregnancy

Irondeficiency

Increaseinaerobiceconomy

Advantages

Prolongedexerciseintheheat

Headache

Endometrialandovariancancer

Disadvantages

Menorrhagia

Nausea

Benignbreastlesions

Box2.Possibleadvantagesanddisadvantagesoforal

Controlofmenstruation

Contraception

Functionalovariancysts

Menstrualmigraines

Potentialcardiovascular&thromboticcomplications

Decreasedinjuries

Dysmenorrhea

Pelvicinflammatorydisease

Rheumatoidarthritis

Increasedligamentlaxitya

contraceptiveuserelevanttosportperformance

Endometrialhyperplasia

PossibleAdvantages

Carbohydratesparing

Fluidretentionandweightgain

candecreasetheironlossthatoccursduringmenstruation,whichisaserious probleminathleticwomen. Box2 liststhepossibleadvantagesanddisadvantages oforalcontraceptiveuseinsportperformance,althoughformanyofthesportrelatedfactors,anunequivocalconclusioncannotyetbemade.

Decreaseinanaerobicperformance

Oralcontraceptivepillsanddrugtesting

a Increasedligamentlaxitymaybebeneficialordetrimentalin differentsituations.

Theissueofweightgain,whichisofgreatconcerntoathletesandcoaches, particularlyinlow–bodyweightsports,shouldbediscussed.Mostofthestudies donotindicateoveralleffectonbodyweightwhiletakingOCPs,andthenewer 20 mg-dosagepillsclaimtohavetheleasteffect.

In1987,norethindrone(norethisterone),aprogesteronefoundinmanyOCPs, wasplacedonthelistofbannedsubstancesbytheInternationalOlympic Committee.Despitethelackofscientificevidenceofanyperformanceenhancement,thiswasdonebecauseofdifficultiesdistinguishingbetweenthemetabolitesofnorethindroneandthoseofnandrolone,acommonanabolic-androgenic steroid.Thisbanwasoverturnedafewmonthslaterthankstotheeffortsof Dr.AndrewPipefromCanadaandothers,whoclaimedthatadrugwithalegitimatemedicalpurposeandwhichisnotperformance-enhancingshouldnotbe bannedsimplybecauseitconfusesthedrug-testingprocess [124].However, becausethecutofflevelforwomenofnandrolonemetabolitesintheurine wasreducedfrom5to2ng/mL,womenonpillscontainingnorethisteronewill usuallyhaveaconcentrationoverthenewcutoff(butlessthan5ng/mL). Currently,WorldAnti-DopingAgency(WADA)laboratoriesareadvisedtocheck beta-hCGwhenawomanhasaconcentrationabove2ng/mLtoseeifsheis pregnantornot,aspregnancycouldexplaintheincreasedvalue.Ifthebeta-hCG testisnegativethelaboratorieswilllookfornorethisteroneinthesample,which wouldexplaintheincreasedvalueofthenandrolonemetabolites.Thedecision, however,isultimatelymadebythesportgoverningbodythatreceivesthe

Uncleareffect Strength

menstrualcycle & sportsperformance e75

Increasedinsulinresistance(dependingontheOCPcomposition) Increasedligamentlaxitya

constantini e76etal

Pregnancy

Overthecourseofanovulatorymenstrualcycle,therearepredicableand measurablevariationsinthefemalesexsteroids(eg,estradiolandprogesterone) thathavemultipleandvariableeffectsondifferentbodysystems.Althoughthere aretheoreticalimplicationsforphysicalandmentalperformanceinsports,the workplace,andspecialpopulationssuchasthemilitary,thereisnoconclusive evidencethatsignificantmenstrualcycledifferencesexist.Anexceptionmightbe apotentialadverseluteal-phaseeffectforenduranceeventstakingplacein extremelyhotandhumidconditions.Theabilitytogeneralizecurrentfindingsis limitedbysignificantmethodologicalproblems,andthereissubstantialinterandintraindividualvariability.Inaddition,thefullspectrumofmenstrual dysfunctionthatisfrequentlyseeninfemaleathletesfurthercomplicates investigationandmanagement.

Therehavebeenanecdotalreportsaboutwomenwhoconceivedtoincrease performance.Thesuggestedmechanismwasthroughanincreaseinlevelsof beta-hCG,ahormonewithsomeanabolicproperties.Additionalhormonaland biochemicalchangesoccurringinpregnancymayalsoplayarole.Nevertheless, thismethodseemsoutofplaceandextremelyunethical,especiallyifanabortion isoriginallyplanned.

Athletesandcoachesshouldbecounseledregardingthemenstrualcycle,its relationtoperformance,thegreatvariabilitythatexistsamongindividuals,and thetherapeuticpossibilities.OCPscontainingsyntheticestrogensandprogestins arethemostcommonlyuseddrugsforcontrollingandmanipulatingthemenstrualcycle,astheyhaveseveraladvantagesforthefemaleathleteinadditionto beingagoodcontraceptivemethod.However,althoughbeingprescribedforover 40years,theeffectofOCPsonperformanceandtheirpotentialhealthadvantages anddisadvantages,especiallywiththenewextendedregimens,arenotclear. Thereisagreatneedforcontinuingresearchinthisareabystudyinglarger groupsofsubjectsincarefullydesignedandcontrolledprospectiverandomized trials,althoughindividualdatacollectionandtailoredtherapyshouldbeapplied foreliteathletes.

laboratoryreport,notthelaboratoryitself.Thelaboratorieswillreportallvalues above2ng/mLandtheadditionaltestsforbeta-hCGandnorethisterone.Toavoid thispotentialconfusion,femaleathleteswhoaresubjecttodrugtestingshould perhapsstayawayfromOCPscontainingnorethisterone,ifpossible(BengtO. Eriksson,ProfessorEmeritus,personalcommunication,2004).

Summary

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