Endometriosis: ancient disease, ancient treatments

62 Pages·2012·14.43 MB·English

Endometriosis: ancient disease,
ancient treatments
CamranNezhat,M.D.,aFarrNezhat,M.D.,b,candCeanaNezhat,M.D.a,d
a Stanford University Medical Center, Palo Alto, California; b Columbia University, New York, New York; c St. Luke's-
Roosevelt'sHospital,NewYork,NewYork;anddNorthsideHospital,Atlanta,Georgia
Ever since Vincent Knapp pub- essential new insights about a disorder mired in inescapable ambiguity, espe-
lished his 1999article ‘‘Howold thatcontinuestoreignasoneofgyne- ciallybecauseconditionslikeappendi-
is Endometriosis?’’ (1), there cology'smostperplexingdiseases. citis, nonendometriotic ovarian cysts,
seems to have been renewed interest infections, and leiomyomas can pro-
inidentifyingjustwhenendometriosis SOLVING THE MYSTERY OF duce similar gynecologic symptoms
was discovered as a distinct disease HYSTERIA (2).However,afterfilteringallhistories
entity. through the lens of modern under-
WasFreudWrongYetAgain?
Whilethehistoryofendometriosis standings, we feel confident that the
With these ideas in mind, we applied
subsequent to its 1860 microscopic following analyses include only those
unveiling by Karl von Rokitansky has abroadersetofcriteriainsearchinghis- patternsofillnessthatsharesignificant
torical records for the earliest possible
been well-studied, its story leading up correspondence to current clinical in-
signsofendometriosis,takingcaretoin-
to that moment has remained largely terpretationsofendometriosis.
clude historical descriptions of clinical
unknown. The time seemed ripe to For our research methodology, we
and macroscopic findings that corre-
castlightonthischasmofhistoryand pursued several strategies, including
sponded to contemporary understand-
give voice to the inaudible narratives traditional searches of the PubMed/
ings. Historical perspectives on pelvic
ofillnessthathavebeenlostinthemar- Medlinedatabases.Additionally,archi-
pain in women have also informed our
gins of centuries. Inexact as the study val research was performed at several
analyses.
ofhistorymaybe,neverthelessclinical locations including the National Li-
Byapplyingthisbroadersetofcri-
observations from the past may offer brary of Medicine in Bethesda, Mary-
teriawewereabletouncoversubstan-
unique perspectives that would other- land; the Lane and Green libraries at
tial, if not irrefutable, evidence that
wisehavebeenentirelyoverlooked. Stanford University in California; and
hysteria, the now discredited mystery
Moreover,insurveyingthehistori- the medical history library of the Uni-
cal development of scientific medicine, disorder presumed for centuries to be versityofCaliforniaatSanFrancisco.
psychologicalinorigin,wasmostlikely
it is evident that nearly all of our In some cases, it was necessary to
endometriosis in the majority of cases
current understandings of complex translate primary sources that were
(Fig.1).Ifso,thenthiswouldconstitute
disease-states have resulted from the availableonlyinLatin.Forthisspecial-
oneofthemostcolossalmassmisdiag-
synthesis of centuries of observations. ized task, we consulted with the
noses in human history, one that over
Even medical theories that ultimately Cambridge-educated Latin and Greek
the centuries has subjected women to
provedtobeexquisitefallacieshaveac- scholar, J. R. T. Holland of Quintus
murder,madhouses,andlivesofunre-
tuallyservedasessential counterpoints LatinTranslationService,whoseexper-
throughouttheages,refiningknowledge mitting physical, social, and psycho- tise in translating medical texts from
logical pain. The number of lives that
by producing the searing clarity that premodern eras proved especially cru-
may have been affected by such
only unanticipated failures can yield; cialfordemystifyingseveralcontested
centuries-long misdiagnoses is stag-
the sort of shock medicine sometimes areasofthehistoryofendometriosis.
geringtoconsider,likelyinvolvingfig-
needstoachievetransformativechange. Newly digitized medical literature
uresinthemultiplemillions.
Viewedinthislight,toexcludethefor- made available by Google Books also
mative years leading up to the micro- provedtobeasurprisinglyusefulnew
scopic discovery of endometriosis is to Methodologies source.Toachieveaninterdisciplinary
deprive our discipline of an invaluable Abroadlydefinedsubjectsuchaspelvic perspective, we also referenced a wide
reservoirofknowledgethatmayreveal painisnaturallyboundtoyieldresults rangeofmaterialfromoutsideofmed-
icine, drawing from the disciplines of
ReceivedJuly31,2011;acceptedAugust1,2011. psychology, literature, art history, and
Theauthorshavenothingtodisclose. medical anthropology. Given the alle-
Reprint requests: Camran Nezhat, M.D., 900 Welch Road, Suite 403, Palo Alto, California 94304
gorical nature of many these alterna-
(E-mail:[email protected]).
tive sources, they were not evaluated
FertilityandSterility®Vol.-,No.-,-20120015-0282/$36.00 inthesamemannerasthemedicalliter-
Copyright©2012AmericanSocietyforReproductiveMedicine,PublishedbyElsevierInc.
http://dx.doi.org/10.1016/j.fertnstert.2012.08.001 ature intended to represent empirical
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FIGURE1 FIGURE2
ReplicaofSigmundFreud'scouch,wherepatientspresentingwith
endometriosis-like symptoms were often diagnosed with hysteria.
(Reproduced courtesy of Konstantin Binder, photograph from the
FreudMuseuminLondon.)
Nezhat.Endometriosisinhistory.FertilSteril2012.
experiences.Rather,theirutilityliesintheiruniqueabilityto
convey otherwise nearly imperceptible cultural undertones,
theprismsthroughwhichillnessesareinvariablyexperienced
andconceptualized.
With thousands of conceivable sources from which to
choose,thisbriefsurveyshouldinnowaybeconsideredan
exhaustive study. Nevertheless, we believe it fills a gap in Expertsonmedievalmedicinedescribethislate13th-centuryimage
from a medical textbook as one depicting a case of uterine
theliteraturebyprovidingamultidisciplinaryhistoricalanal- suffocation, a disease profile with many similarities to
ysisofendometriosisasitmayhavebeenconceptualizedbe- endometriosis. (Reproduced with permission of Oxford University,
fore its 1860 microscopic discovery by Rokitansky. We first BodleianLibrary,MSAshmole399,f.33–34.)
presented the preliminary results of this research in March Nezhat.Endometriosisinhistory.FertilSteril2012.
2011,attheWorldEndometriosisSymposiumheldinAtlanta,
Georgia.
awomansufferingfromwhatwasusuallycalledatthetime
‘‘strangulation or suffocation of the womb.’’ The linguistic
lineagesofthesetermsarestillcontested,butmanyscholars
TheSearchBegins
believe their roots can be traced to the hysterikos-hysterike
Historicalrepresentationsofpelvicpain:Oxford'sBodleian pnixfamilyofdisorders,looselydefineddiseaseframeworks
LibraryMSAshmole399. Webeganouranalysisbyfocus-
formulated byHippocratic andotherGreco-Roman authori-
ingfirstonthebroadestcategoryunderconsideration:histor-
tiesthroughoutClassicalandLateAntiquity,andtheoriginal
icalrepresentationsofpelvicpaininwomen.Asitturnedout, sourceofthewordhysteria(4–7).
thissubjectprovedratherelusive,onecuriouslyandconsis-
tentlyneglectedinthearchivesofhistory.Detailedaccounts
CLASSICAL AND LATE ANTIQUITY
ofmenstrualpaininparticularwererarelyifeverchronicled.
TheAnimalisticWomb
Yetthehundredsofmedicantsforgynecologicailmentslisted
inthevariousMateriaMedicasthroughouttheagesprovide Althoughstrangulation orsuffocationofthewombtookon
in themselves a strikingly different account, articulating by manycontradictorymeaningsthroughouthistory,theirearli-
proxystoriesofillnessthatbeliethosefoundinmainstream est antecedents mayhave stemmedfrom concepts first pos-
medicalliterature. ited by the ancient Egyptians as long ago as 1855 BC.
Itwasbytracingthesenearlyimperceptibleleadsthatwe However, they were later popularized by the Hippocratic
eventuallystumbleduponalate13th-centurymedicalman- texts,Plato,andotherGreco-RomansourcesofClassicalAn-
uscript,referredtoasMSAshmole399(folios33–34)inwhich tiquity(8)(Fig.3).Thebasicconceptunderlyingthesedisor-
images ofa womanapparently doubled overinpain can be ders rested on the premise that the uterus was not actually
found(3)(Fig.2).Althoughtherearenotextstoaccompany aregularorgan,butratheronemoreanalogoustoalivean-
theoriginaldrawings,expertsbelievetheimageryrepresents imal,hungryformotherhood.
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consultingnumeroussources,weidentifiedseveralrelatively
FIGURE3
unambiguous disease profiles that allude to the wandering
wombandothersymptomssuggestiveofendometriosis.The
correlationsbecomeparticularlyevidentwhenwelearnthat
theHippocraticsviewedthefollowingfourfactorsashighly
predictiveofgynecologicdisease:[1]menstrualdysfunction
is a cause of disease, [2] pregnancy is a possible cure, and
[3–4]painandinfertilityaspotentialoutcomesifthewoman
isleftuntreated(7).Nearly2500yearshavepassedsincethese
observations were made, yet remarkably they correspond
nearlyseamlesslytothesetofsymptomsidentifiedtodayas
emblems ofendometriosis. Itisunfathomable thatsuchun-
cannycorrelationscouldremainsuspendedinatimelesssta-
sis for so long. But what is even more incomprehensible is
how such a uniquely patterned symptom profile could exist
forageswithoutothersrealizingitwasthehallmarkofadis-
tinctdisease.
Itwasmostlikelytheendlessupheavalsofmedievaltimes
thatleftsuchcrucialHippocraticinsightsburiedinthedebris
ofhistory.Thisisthemostplausibleexplanationbecause,as
wewillsee,thesefourcoreassumptionswouldinformessen-
tiallyallGreco-Romanideasofwhygynecologicaldisorders
arise up until about the fifth century AD, the period many
markasthebeginningoftheEuropeanMiddleAges.
The Hippocratic texts provide many examples of how
thesefourcoreconceptsnotonlyinfluencedancientdiagnos-
ticsandprognosticsbutalsocloselyparalleledmodernviews.
Forexample,inanearconceptualequivalenttothe20th-cen-
In the Hippocratic Corpus several gynecological symptoms are
mentioned,whichbearstrikingsimilaritytothoseofendometriosis, turynotionofendometriosisasa‘‘careerwoman'sdisease,’’
including uterine ulcers, adhesions, and infertility. (Page of text in the Hippocratics suggested that delaying motherhood could
‘‘Aphorismi’’ with an illuminated small ‘‘M,’’ Record UI. 1014450-
trigger disorders of the uterus, with painful menstruation
55, In: Hunayn ibn-Ishaq al-'Ibadi, Oxford, 13th century, l. 19v,
Isagoge and other medical texts, Census 78. Reproduced courtesy citedasonesuchoutcome.
oftheU.S.NationalLibraryofMedicine.) Womenwhosufferedfromdysmenorrheaweretherefore
Nezhat.Endometriosisinhistory.FertilSteril2012. urgedtomarryandconceiveasquicklyaspossible(15).
Other dire consequences were predicted for those who
failed to partake in the pregnancy prescription. One Hippo-
Though a metaphorical rather than literal analogy may craticauthorwarnedthat‘‘iftheyhaveneverbeenpregnant,
havebeenintended,theideaoftheanimalisticwombeventu-
thederangedstateofmenstruationismorecommonandmore
ally began informing everyday practices. From this pretext dangerousthanwhentheyhavebornechildren’’(aparaphrase
emerged one of ancient medicine's most enduring dogmas, bythetranslator)andthatshewillbe‘‘release[d]fromthisdis-
theideathatifawomandidnotfulfillthesociallyproscribed ease,whensheispregnant’’(4,7).
roles of marriage and motherhood her uterus would be de-
Childlessnessinolder,marriedwomen(i.e.,casesofpre-
privedofitsintendedpurpose.Fromthispresumedunnatural
sumed infertility) was recognized as another predisposing
state,itwasbelievedthattheuteruswouldbegintowander
factor for gynecologic disorders (4). Drawingfrom the same
about—thefamouswanderingwomb—andthuscontributeto
pregnancy-as-therapyorthodoxy,anothergroupbelievedto
theonsetofallmannerofillness(5,7,9–14).Thenotionof
beparticularlysusceptibletogynecologicdisorderswerepre-
a wandering womb naturally strikes a modern audience as
sumablyfertilewomenwhoneverthelessremainedchildless;
an anatomic impossibility. Yet it suggests a causal
youngwidowsandvirginswhohadalreadymenstruatedbut
connection with pregnancy that is nearly identical to remained unmarried typified this category of susceptible
a modern assumption about endometriosis: the idea that
females(4,16).
pregnancycantemporarilysuppresssymptoms.
Detailed reports of menstrual disorders. Detailed accounts
of other menstruation-related disorders were reported in
TheHippocraticCorpus a chapter titled ‘‘Aphorisms,’’ in which the Hippocratic au-
Thesetheoriesinformmanyofthemedicalpracticesdescribed thor describes menorrhagia as a potential cause for pathol-
intheHippocraticcorpus,acompilationofworkswrittenby ogy (16) and proclaims: ‘‘When the menses are excessive,
variousauthorsthroughoutthe5ththrough4thcenturiesBC. diseases take place’’ (17). It was also observed that in some
The translations of these Hippocratic texts have been the women their ‘‘floodings,’’ an archaic term for menstruation,
subject of academic debate for centuries. However, after were followed by ‘‘grumulous clots . . . accompanied with
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FIGURE4 FIGURE5
Lyttavesicatoria,knowninmoderntimesastheaphrodisiacSpanish
fly,wasoneofmanypharmaceuticalsprescribedintheHippocratic
Corpusfortreatingmenstrualdisordersandinfertility.(Reproduced
courtesy of Christophe Franco, http://en.wikipedia.org/wiki/
File:Lytta-vesicatoria.jpg.)
Nezhat.Endometriosisinhistory.FertilSteril2012.
tobesterility’’(16).Someofthesetranslationsarestillthesub-
jectofheatedacademicdebates,particularlytheterm‘‘hysteric
Allegoricalimageoffumigation,asdepictedinJohnCollier'spainting
‘‘PriestessofDelphi,’’1893.(ReproducedwithpermissionoftheArt paroxysms.’’Yetbasedonthetextualevidenceinitsentirety,it
GalleryofSouthAustralia,Adelaide.) isatleastreasonabletosurmisethattheseHippocraticphysi-
Nezhat.Endometriosisinhistory.FertilSteril2012. ciansmayhavebeenencounteringendometriosis.
Medicaltherapies. Thetypesoftherapeuticoptionsavailable
weregenerallyingestibleconcoctions,fumigants,orsuppos-
itoriesthatcontainedsuchsubstancesastheurineofmenor
pain,inflammationoftheuterus,[and]hystericparoxysms.’’
bulls, tar water, chaste tree (Vitex agnuscastus), pomegran-
Additionally, in the Hippocratic chapter titled ‘‘Diseases of ates, cantharides, or castor oil (Figs. 4–6). In analyzing the
Young Girls’’ (translated less accurately today as ‘‘Virgins’’),
histories of these individual substances, we came across
the authors observed that ‘‘the menses sometimes suddenly
somesurprisingresults.Themedicinalusageofcantharides,
appear abundantly at the end of three months, in clots of
for example, has an especially colorful history; although it
blackblood,resemblingflesh;sometimesulcersoftheuterus
is actually derived from dried beetles, throughout history it
ensue, requiring much attention’’ (16). The Hippocratic au- cametobeknownastheinfamousaphrodisiac‘‘Spanishfly.’’
thorgoesontoreport:‘‘Wheninadiseasedstate,themenses
Pomegranatesandchastetreealsoweredeployedforcen-
are of a bilious character; they have a black and shining
turies as contraceptives and treatments for menstrual disor-
appearance . . . and are accompanied with an erratic fever,
ders.KnownasshíliuinChinese,thepomegranatehasbeen
chills, nausea, and heartburn.’’ Allusions to perhaps bowel
traditionallyviewedinChinaasasourceandsymboloffer-
or lung endometriosis are also evident in the observation
tility(18).Recentstudieshaveevenbeguntoanalyzeitspur-
that ‘‘sometimes the menses are vicariously discharged by
portedantiproliferativeandantiaromataseproperties(19).
vomiting or stool; more commonly is the case with virgins
Incontrast,thepineresin-derivednostrumknownastar
than with married women.’’
water was practically incompatible with life (21). The same
Uterineadhesionsandulcers. Inthechapter‘‘OntheNature foul substance Charles Dicken's character Pip was forced to
ofWomen,’’welearnthattheHippocraticswerealsofamiliar ingestaspunishment,tarwaterwasconsideredbytheHippo-
with uterine adhesions. As the translator of these texts ex- craticsassoeffective(orsoodious)thatwomenofantiquity
plained,theyadvisedthat‘‘incaseofadhesionsbetweenthe werewarnedtheywouldbe‘‘barrenforever’’iftheyingestedit
uterus and other parts, indurations, suppuration of the (20,21).Fragmentsofthisbeliefappeartohavebeenhanded
womb,andulcers,sometimesarise,ordischargeswhichprove downovertimebecausetodaysomeveterinarianstudieshave
fatalifnotattendedto;fomentationsofurineareamongthe shown pine extracts to exert modest anti-fertility effects in
measuresrecommended.Theusualeffectofthisstateissaid animalmodels(22,23).
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FIGURE6 FIGURE7
Uterine suffocation, vaginal prolapse, and other gynecologic
conditions were sometimes treated with succussion, the ancient
Greek practice in which patients are bound to a ladder, turned
upsidedown,andshakenvigorously,withtheideabeingthatthe
Recentstudieshavebeguntoanalyzethepurportedantiproliferative uteruswouldbeshakenbackintoitsproperposition.(Reproduced
and antiaromatase properties of pomegranates, prescribed for courtesy of BioMed Central Ltd and SpringerImages. Scoliosis
fertility and menstrual disorders in both Hippocratic Medicine and 2009;4:6. Image from the illustrated comments of Apollonius of
ancient Chinese medicine. (Reproduced courtesy of Benjamin Kitium on the Hippocratic treatise On Articulations. Bibliotheca
Trovato,http://en.wikipedia.org/wiki/File:PomegranateChina.jpg.) MedicaLaurenziana,Florence.)
Nezhat.Endometriosisinhistory.FertilSteril2012. Nezhat.Endometriosisinhistory.FertilSteril2012.
woefullyinadequate(26).Evenso,furtherinvestigationsmay
Asfortheuseofurineformedicinalpurposes,inmodern
bewarranted.Asreportedinarecenteditorialbyendometri-
gynecologywearenodoubtfamiliarwiththeuseofpregnant
osisexpert,Dr.LindaGiudice(2),preliminarystudiessuggest
mare urine extracts as Premarin's main ingredient. What is
that:‘‘Chineseherbaltherapieshaveexhibitedantiprolifera-
less clear is whether the ancients would have been capable
tive, antinociceptive, and prosedative properties, as well as
of extracting similar hormone-disrupting constituents from
anti-inflammatory actions, antioxidant characteristics, sup-
theurineofbullsormen.Theliteratureprovidesfewexamples
pressionofCOX-2andcytokines,andmechanismsinvolved
ofwell-designed,peer-reviewedstudiesinhumans,butsev-
in the cytokine response, such as inhibition of NF-KB’’
eralanimalstudiesdosuggestthatbullurinecanexertanti-
(19,22–24,27).
estrogenicpropertiesinmice(24).
Othermoreinventivetherapieswereexploredaswell.One ‘‘Extremest anguish.’’ Although we do not usually think of
ofthemostunusualtherapieswasthepracticeofsuccession. the acclaimed philosopher Plato (375 BC) as being involved
Designedasamechanicalmeansforrepositioningtheuterus, in medicine, this did not stop him from expressing his own
asessionofsuccussioninvolvedtyingthepatienttoaladder, opinionsaboutgynecologicdisorders.Infact,Platowasactu-
whichwouldthenbeturnedupsidedownandshakenupand allyamongthefirsttomentiontheextremepainthatwomen
down until the womb returned to its rightful place (25) sufferedasaresultsuffocationofthewomb.Heexplainedthat
(Fig. 7). In thiscase, visiblyprolapsed uteri were most likely thedisorderistriggeredwhen‘‘thewombremainsbarrentoo
theintendedtarget,makingthepracticeinfinitelymorecom- long after puberty, is distressed and sorely disturbed, and,
prehensiblefromamodernstandpoint. straying about the body and cutting off the passages of
Admittedly our analyses of ancient pharmacology are breath, it impedes respiration and brings the sufferer into
speculative at best, given the absence of high-quality the extremest anguish and provokes all manner of illness
evidence to support these theories. As Renckens argues so besides’’(28,29).
effectivelyinhisarticleaboutalternativetreatmentsinrepro- BythetimeRomanscholarPlinytheElder(23–79AD)be-
ductivemedicine,muchoftheexistingevidenceappearstobe gan reporting on suffocation of the womb, several new
VOL.-NO.-/-2012 5
accurate anatomic descriptions of the uterus actually call
FIGURE8
intoquestionotherhistoricalaccountsthatclaimhumandis-
sectionshadbeenallbutabandonedbythattime.
Asforthosesusceptibletouterinedisorders,Soranusre-
portsthattheconventionalviewsofhisdaywerethat‘‘many
women, menstruating with difficulty and pain because of
a long widowhood, have menstruated freely after marrying
again,’’withmarriageimplyingthattheconceptioncurative
would soon follow (15, 30). In another chapter Soranus
revisits the topic from a different angle, explaining again
that many physicians view pregnancy as healthful because
it was believed that ‘‘some women, menstruating with
difficulty and suffering uterine pressure, have been freed of
theirtroublesafterpregnancy’’(15).
Othersymptoms. Investigatingtheothersymptomsascribed
overtheyearstosuffocationofthewombisacomplicatedmat-
ter.Yetaftercarefulevaluationofresearchbyseveralscholars
specializinginwomen'sancientmedicine,weroundedupall
thedisparatedescriptiveevidenceandfoundthatconvulsions,
epileptic-like‘‘fits,’’abdominalpain,nausea,vomiting,diges-
tive disorders, gritting of the teeth, excessive perspiration,
palpitations, ashen skin, and the appearance of lumps near
theabdominalsidewallswereallamongthemostcommonly
cited symptoms (5, 9, 10, 12). The observation of lumps
appearing to the side of the uterus was a symptom that
piquedourinterestconsiderably,butseveralinsurmountable
translational ambiguities made it quite difficult to extract
anyadditionalinsightaboutthisparticulardescription.
SoranusofEphesus(circa98–138AD)describedmanyendometriosis- Convulsive symptoms as part of gynecologic medicine
likesymptoms,includingmenstrualdisordersthatledtoinfertilityand representanotherintriguingchallengetoourmodernconcep-
casesofuterinesuffocationthatcausedviolentuterinecontractions.
tionsofdiagnosticcriteria.Asitturnedout,theoriginalmean-
(Reproduced courtesy of the U.S. National Library of Medicine;
Portraitno.6313-A.) ingofhystericalconvulsionsduringthiseragenerallyreferred
Nezhat.Endometriosisinhistory.FertilSteril2012. towomenfallingtotheground,doubledoverintoafetalpo-
sition.Suchdescriptionscorrespondwelltotheimagesfound
intheMSAshmole399drawings,andtheycouldveryeasily
observations had been added to the diagnostic profile. In- bedescribingaresponsetoacuteabdominalpain(5).
cludedamongthesewasanaccountofthedisorder'speculiar
abilitytoreducewomentosomesortofsemiconsciousstate,
Celsus
lying‘‘asifdeadforsevendays’’(7).
Reports of women suffering from convulsions and/or
epileptic-like symptoms in association with suffocation of
Soranus
thewombcontinuedtobementionedbythenextgeneration
Inflammationoftheuterus. Aboutacenturylater,Soranus ofmedicalscientists.RomanscholarCelsusdescribedwomen
(ca.98–138AD)reportedsimilarfindings,butofferedcritical sufferingfrom‘‘violent’’illnesscomingfromthewomb,who
new clinical insights when he explained that women were fall down as if suffering from epilepsy. However, ‘‘rather
fallingunconsciousasaresultofthedisorder'scharacteristic thanexhibitingthenormalsignsassociatedwiththatdisorder,
violent uterine contractions, which Soranus observed could suchasfoamingoreyesrollingback,instead[they]liedownas
manifestineither chronicoracuteforms(7)(Fig.8).Toex- ifinsleep’’(Fig.9).
plainthesesymptoms,Soranusdepartedfromtraditionbybe- Ofparticularnote,Celsusreportsthat,insomecases,the
comingthefirsttosuggestinflammationoftheuterusaspart disease returned frequently and that ‘‘some women suffer
ofhisradicalnewtheoryabouttheoriginsofsuffocationof from this their entire lives’’ (4, 7, 29). This specific
thewomb. observation proves especially relevant in view of our
More than just an essential new theoretical framework, currenthistoricalstudyofendometriosis,butitwasCelsus's
Soranus'sdetailedmacroscopicknowledgeoftheseandother reports alluding to violent fits of the womb that seemed to
uterine pathologies supports the idea that human autopsies attract the most attention throughout the ages. Some
may have informed his views. Although Soranus admitted scholars even have suggested that Celsus's comment was
tohavingperformedautopsies,theywouldhavebeenconsid- theoriginalsourcebehindtheterm‘‘hystericfits.’’
eredhighlyunorthodoxandsomewhatriskyforthetimes.In- DespiteboththeHippocratics'andCelsus'sunambiguous
deed, unassuming as this revelation may seem, Soranus's explications of a gynecologic disorder distinct from regular
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FIGURE9 FIGURE10
Second-centuryGreekencyclopedistCelsus(circa25BC—circa50),
described cases of a violent uterine illness that caused women to
fall to the ground, convulsing and fainting from attacks of acute
pain. (Reproduced courtesy of the U.S. National Library of
Medicine,PortraitNo.B04927,titled‘‘A.C.Celse’’ byPierreRoch In Greek physician Pedanius Dioscorides's acclaimed work, De
Vigneron,Paris,1865.) materia medica (circa 77 AD), uterine suffocation is described as
Nezhat.Endometriosisinhistory.FertilSteril2012. a menstrual disorder with many parallels to endometriosis.
(Reproduced courtesy of the U.S. National Library of Medicine,
PortraitNo.1550.3,anonymousworktitled‘‘DioscoridesPedanius
epilepsy,overtheyearstheboundariesseparatingthetwodis- ofAnazarbos.’’)
ordersbecamemorediffuse,leadingtoacontinuedconflation Nezhat.Endometriosisinhistory.FertilSteril2012.
ofepilepticfitswithhystericfits.Thispracticewouldlaterfig-
ure into a series of rather curious theories that developed
aboutwomenandillnessinsubsequenteras(31).
Medica, Dioscorides still provides fresh new perspectives
about menstrual dysfunction and a uterine disorder named
Dioscorides ‘‘strangulation of the uterus,’’ which exhibits the same
Just a few decades after Celsus, one of the most celebrated tendency as suffocation of the uterus to render women un-
physicians of Late Antiquity emerged, the Greek physician conscious.Likehispredecessors,Dioscoridesdescribesadisor-
PedaniusDioscorides.HisDeMateriaMedica(ca.77AD)stood der that causes women to suddenly fall down, apparently
foragesasoneofthemostinfluentialancienttreatisesinWest- hovering either in some sort of quasi-conscious state or in
ernmedicine,‘‘thechiefsourceforherbalistsofallnations’’and anotherwisediminishedconditionthatrendersthemunable
compulsoryreadinginmedicaleducationformorethan15cen- to raise themselves to a standing position. As noted before,
turies (32, 33) (Fig. 10). Dioscorides'stext differsfrom others manyofthesesignscouldsignifyresponsestoacuteattacks
reviewed so far in that it is organized in an encyclopedic of pain. That the afflicted women are lying down in some
format.Enumeratingnearly1,000pharmacologiccompounds fashion can be established by a prescription for shellfish
in a descriptive manner, though without commentary on shells that is believed to help ‘‘rayse up such women as are
presumed etiologies, the encyclopedic organization can be troubled with strangulatus uteri, & such as have ye falling
disorienting. However, it reflects the best pharmacologic sicknesse’’(32).
science of the day, offering an informative narrative about
Medication. Views about menstrual disorders were surpris-
1st century medical practices and furnishing some insight
inglyadvanced,withDioscoridesclearlyacknowledgingmen-
into gynecologic disorders as they were understood and
strual pain as an organic, pathologic condition requiring
treatednearly2000yearsago.
medication, something that even some 21st-century physi-
Pain and collapse. Though the theoretical continuity con- ciansfailtorecognizeattimes.Asformedicinal substances,
cerning uterine suffocation is clearly evident in De Materia the inventory abounds with prescriptions for such items as
VOL.-NO.-/-2012 7
bedbugs,brains,humanurine,andotherdecidedlyindelect- Another modern study found that, of several medicinal
ablemorsels.Wewillsparethereaderthesedetailsandoffer herbsbelievedtohavebeenusedsinceantiquity,‘‘20showed
insteadexcerptsoftheleastodiousmedicaltherapies,oneof strongand10weakanti-oestrogenicactivity.’’Amongthose
which is a dysmenorrhea treatment described as ‘‘the horne foundtohavestrongantiestrogenicactivitywasprunellavul-
ofanHartbeingburnt&washt,ifitbedranckthequantitie garis(commonlycalledSelf-heal,orXioakucaoinMandarin
of twoe spoonfuls . . . It is good also for women troubled Chinese),anherbusedinHippocraticandtraditionalChinese
withyeflux(ofyewombe)beinggivenwithsommeliquorfit- medicine for centuries to treat dysmenorrhea (34, 35).
tingforthatgrief’’(32). Whatever the case, it is clear many of these ancient beliefs
AsforDioscorides'sreferencesto‘‘womentroubledwith survived the journey through time, as red deer antler and
ye flux’’, naturally many so-called troubles aside from dys- other products touting hormone-altering properties are still
menorrhea could be correlated with menstruation, such as offeredtodayinalternativemedicine.
amenorrhea,anemia,ormenorrhagia.However,basedonev-
idencederivedfrom otherpassages,itappearsthatDioscor-
ides was likely referring specifically to menstrual pain and Galen
the other symptoms associated with strangulation of the Violentuterinecontractionsandinflamedligaments. Prac-
uterus. Further evidence substantiating this view can be in- ticingmedicineaboutacenturyorsoafterDioscorides,Clau-
ferred by the fact that those other menstrual disorders were diusGalenofPergamon(129–216AD)hadathisdisposalmore
assignedtheirowndistinctiveremedies. than500yearsofmedicalheritageconcerningsuffocationof
the womb,a disease entitywith a symptom profile that had
Menstruation suppression. Dioscorides's work is remark-
able for another reason, as it appears to be the first of its remainedstableforcenturies(7)(Fig.11).Althoughconvul-
sionsandfitscontinuedtobetheheadlinesymptoms,Galen
era to mention in unequivocal terms medications designed
offered fresh new insights, including oneof the clearest de-
to suppress menstruation. Like the Hippocratics 500 years
scriptions of symptoms suggestive of adhesions and/or
earlier,itdemonstratesthatDioscoridesrecognizedmenor-
endometriosis-infiltratedligaments.
rhagia not only as a distinct menstrual variation but as
Galenprovidedthesenewclinicalsymptomsaspartofhis
a potentially pathologic disorder in need of medical inter-
proposedtheoryofpathogenesis,whichsuggestedthatsuffo-
vention (32). For this ailment, Dioscorides suggested that
the brain of a hare, ‘‘being dranck after three dayes after cationofthewombwastriggeredwhenthemembranesthat
ye menstrual courses,’’ is reported to cause sterility; like- anchortheuterus inplacebecame engorged astheresultof
wise, it stops the ‘‘flux of ye wombe and of the belly’’ excessivemenstrualblood.Galenbelievedthatthisexcessive
(30, 32).
This was a particularly interesting discovery because FIGURE11
manyhistorians specializing inwomen's medicineofantiq-
uityhavereportednearlyexclusivelyonmedicantsprescribed
forinducingmenstruation,putativelyforcasesofamenorrhea
but that many believe were actually intended as abortive
agents. Without this critical insight offered by Dioscorides,
the ancient world, as interpreted in modern times, would
appeartobeoneeithernearlydevoidofanymenstrualdisor-
ders other than amenorrhea or rife with epidemic abortive
practices.
Asmentionedbefore,naturallyaretrospectiveevaluation
oftheefficacyofthesesubstancesisimpossible.Inanycase,
themajorityofmodernbiochemicalstudiesthatattemptedto
measure the efficacy of ancient pharmacologic substances
haveprovedinconclusiveatbest.However,afewstudiesus-
inganimalorinvitromodelshavepointedtopossibleminute
tracesofhormone-disruptingagentsinmedicantsbelievedto
havebeenusedinantiquity(34–37).
RegardingDioscorides'sprescriptionforthehornofahart
to treat menstrual ailments, our research found that ‘‘hart’’
wastheBritish namefor a male stagof thereddeer species
common throughout Europe and Asia Minor (38). In tradi- Claudius Galen of Pergamon (129–216 ACE), Roman physician of
tionalChinesemedicine,reddeerantlerhasbeenusedtotreat Greek heritage, described a gynecologic disorder that produced
violent and painful uterine contractions and swollen and inflamed
male impotence and gynecologic disorders in women (2). A
ligaments. (Reproduced courtesy of the U.S. National Library of
recent animal study from an alternative medicine journal Medicine,CallNo.WZ348C25,no.51sol.PaintingbyRobertA.
evensuggeststhatsomeantlervelvetproductsmay‘‘produce Thom [1952] titled ‘‘9. Galen—Experimenter in Compounding’’
anti-inflammatorycompoundsthatassistintheregulationof [131–201AD]).
prostaglandins’’(39). Nezhat.Endometriosisinhistory.FertilSteril2012.
8 VOL.-NO.-/-2012
FertilityandSterility®
pressure on the ligaments caused the membranes to thicken
FIGURE12
and stretch with tension, which in turn pulled the uterus
into contorted positions. In turn, Galen surmised that these
contortionswerecausingthepainfulandviolentuterinecon-
tractions, lacerations, and inflammation from the repeated
physicalfriction(7).
Aretaeusconcurrence. Aretaeus,acontemporaryofGalen's,
provided nearly identical descriptions, suggesting that the
uterus'smembranesunderwentmorphologicchangesduring
menstruation,resultingindistendingorcontractingmotions
‘‘like the sails of a ship’’ (7). Allusions to violent symptoms
and instances of unexpected deaths were beginning to be
mentioned with greater frequency by this time. Aretaeus
went ontodescribesuffocation ofthewombasacondition
triggered‘‘when[the]wombmovesupwards’’and‘‘pressesvi-
olentlyonintestines’’;itcauses‘‘exhaustion,lossofcontrolof
theknees,dizziness,...herlimbsareweakened,’’and‘‘itre-
sembles epilepsy’’ (30, 40). Expressing sentiments with
uncanny parallels to modern concerns about productivity,
Aretaeus even notes that, when the disorder is severe, there
will be ‘‘hesitation in doing her tasks’’ (30, 40). For those
attacks that have an acute onset, Aretaeus advised that it The reintroduction of supernatural disease etiologies in Western
was essential for a physician to be summoned quickly to medicineoccurredmostdramaticallyduringtheMiddleAges,when
pandemicsliketheplaguewipedoutanestimated30%to60%of
prevent death, an outcome that Aretaeus considered
Europe'spopulation.Itwasduringthistimethatuterinesuffocation
unexpected and difficult to believe as the woman just began to be misconstrued as the work of witchcraft or demonic
momentsbeforehadnotappearedsogravelyill(29). possession. (Reproduced with permission of the British Library
Board (C), Record Number: c6541-07, Shelfmark: Royal 6 E. VI;
Psychologicalfactors. Inwhatmayhavebeenthefirstfate- Page Folio Number: f.301: Plague victims etching by James le
fulmomentswhenpsychologicalelementsbeganfusingmore Palmer,titled‘‘OmneBonum.’’)
consistently with gynecology, Galen contributed another Nezhat.Endometriosisinhistory.FertilSteril2012.
original if notorious observation. He made what appears to
beoneofthemostexplicitreferencesassociatinguterinedis-
orderswithmentalillnesswhenhehypothesizedthatyoung thehighrateofinfantandchildmortality.Meanwhile,with
widows,stillviewedasparticularlypronetouterinedistress, breastfeedinglastinguptotheageof2yearsforeachchild,
couldbe‘‘driventomadnessasaresultoftheirlossofsexual these culturally normative behaviors could have functioned
fulfillment’’(41).Althoughthereweresomewhatsimilarallu- asanaturalsuppressantofthedisorder(ifitwasendometri-
sionsmadeinearlierworks,includingtheHippocratictexts, osis).Therefore,manysuccessiveyearsofchildbearingcould
Galen elaborated on these notions with such authority that haveindeedmadeitappeartohavebeencured(4).
hisworkmayhavebeenthecatalyzingforceresponsiblefor Whenoneconsidersthatsuffocation/strangulationofthe
ushering in a disturbing new era in women's medicine, womb was also believed to be triggered by what was called
when gynecologic ailments firstbegan tobeconceptualized ‘‘spoiledmenstrualblood’’or‘‘spoiledseed’’—inotherwords,
aspsychologicalinnature.Assubtleasthistheoreticalshift anotherassociationwithmenstruation—thenthenotionthat
mayatfirstappear,itsrepercussionswouldproveboundless, these ancient physicians may have been witnessing some
ripplingthroughtheverycoreofsocialandscientificbeliefs casesofendometriosisisallthemoreplausible(5).
forcenturies.
Translation ambiguity. Compelling though these historical
vignettesmaybe,weareobligedtomentionthemanyinev-
FinalThoughts
itableshortcomingsoftheseinvestigations.Tobeginwith,it
With young girls who had begun menstruating considered iswellknownthatanalyzingancienttextswiththeintention
particularly vulnerable to gynecologic dysfunctions and ofimportingmeaningbackintoamoderncontextisanen-
pregnancy considered a possible cure, Western medical au- deavor fraught with unavoidable translational and cultural
thoritiesthroughoutClassicalandLateAntiquityestablished misinterpretations. Thus, the resulting analyses may be
theappropriateageofmarriageassometimewithinayearof moreconjecturalthanconclusive.ThatmostEnglishtransla-
menstruation, whichwasestimatedtobeapproximatelythe tionsavailabletoustodayhaveundergonealinguisticjour-
agesof14to15duringthatperiod(4).Hadsomeofthesecases neyfromGreektoSyriactoArabictoLatintoEnglishisjust
actuallybeenearlyobservationsofendometriosis,conception oneexampleofhoweasilytheoriginalmeaningscouldhave
asapotentialcurewouldhaveappearedquiteefficacious.Af- been distorted. Complicating matters further is the fact that
ter all, women during this era usually began conceiving in many of the ancient texts were derivative works, passed
their teens and raised an average of five to six children, downasnearlyverbatimtranscriptionsofpreviouspublica-
thoughprobably experienced evenmorepregnancies dueto tions. This means that one can never be entirely certain
VOL.-NO.-/-2012 9
whether ancient authors were reporting their own indepen- wars,plagues,andpestilence,itiseasytoseehowsuchim-
dently obtained observations or were simply presenting the pressions were formed, especially when compared with the
clinical experiences of othersastheir own. Of course,today grandluminositythathadbeenGreco-Romanmedicineand
such practices are considered the ultimate in scientific that was now evident in the scientific renaissances that
sacrilege. wereoccurringinAsiancenters(42)(Figs.12and13).Indeed,
Naturally,thevarioussymptomsdescribedcouldalsoap- progressinEuropeanmedicineseemedtogrindtoascreeching
ply to dozens of other disorders. The contorting spasms, for halt.Someexpertshavecharacterizedthisstagnationasape-
example, could have been caused by tetanus, thought to riod spanning 900 years, from about the 5th through 13th
havebeensomewhatprevalentinthosetimeframesandgeog- centuries.
raphies(30).Asadmittedfromtheoutset,withouthistopath-
ologic confirmations, concreteconclusions cannotbemade.
EarlyMiddleAges(5thto11thcenturiesAD)
Yet when viewing the textual evidence in its totality, it is
fair to assume that at least some of these cases could have Supernatural versus superscientific. In theapparentscien-
beenunwittingearlydescriptionsofendometriosis,evende- tificvoidoftheMiddleAges,theologicalandsupernaturalin-
spitesomeareasofambiguity.Overall,thepreponderanceof fluencesreturnedtotheforefrontofthepopularimagination.
evidencegivesreasonforpause.Itisclearthatthehysterikos Suchbeliefscompetedalongsideandattimesedgedoutmuch
familyofdisorderswastosomedegreeaveritablediagnostic ofthehard-wonscientificheritagethathadbeensometicu-
junk drawer. However, the continuity of core assumptions- lously synthesized throughout antiquity. It did not help that
such as viewing pregnancy as a potential cure for painful such revered scholars as Lactantius (4th AD) questioned the
menstruation- which occurred in concert with the equally needforanyfurtherscientificinquiry,asking,‘‘Whatpurpose
suggestive symptoms of vomiting, ‘‘violent pain coming does knowledge serve . . . what blessing is there for me if I
fromthewomb,’’andpainful,blood-filledmembranesserves shouldknowwheretheNilerises,orwhateverelseunderthe
ascredibleevidencethatwearewitnessingtheformativeout- heavensthe'scientists'raveabout?’’(42).Insuchanenviron-
linesofadistinctdiseaseparadigmedgingintoexistence(7). ment,miraculouscuresanddemonicpossessionsalikebecame
plausibletheoriestoexplainhealthandsickness.Asonehisto-
riandescribedit,‘‘illnessmetaphorswerethoseofsin’’orwere
THE MIDDLE AGES invoked ‘‘asa salutary tool toscarepeoplestraight,withvi-
Asepochsgo,theEuropeanmedievalera—theso-calledDark sionsofhelldraggedoutforspecialeffect’’(42)(Fig.14).
Ages—is often conceptualized as though it were one vast Aswewillsee,thesedevelopmentssomehowinsinuated
expanse of scientific and cultural stagnation. Considering themselvesintotheouteredgesofwomen'smedicine,becom-
thatEurope wasravagedbyasuccession offallingempires, ing the theoretical backdrop from which both social and
FIGURE13
Thewidespreaddevastationcausedbytheplaguewasfollowedbyunprecedentedreligious,social,andeconomicupheavalsthatprofoundly
affected thecourseof European history. (Reproducedcourtesy of theU.S. National Library of Medicine, ‘‘Epidemics Die Pest, Plague scene’’
[Plaguevictimsincitysquare],CallNo.WA100C25No.6box12sub.)
Nezhat.Endometriosisinhistory.FertilSteril2012.
10 VOL.-NO.-/-2012