'I'hii-rv. \ l . : (# viliirco|o»ia /.'W. I.

Irre g u la r Shedding o f the E n d o m etriu m

A clinical study including observations concerning the liisto-pathological changes
in the blood vessels of the cndoinctritun

By Michel T H IE R Y *

I N T R O D U C T IO N

M enorrhagia is a sy m p to m caused b y system ic diseases as well as

1>\ a great v a rie ty of local, organic or fu n ctio n al co nditions. O ur
u n d e rsta n d in g o f th e m echanism o f functional m en o rrh ag ia is in­
com plete and acco u n ts for th e lack of rational classification w ithin
the gro up . Som e progress has lately been m ade in this direction by
the renew ed in te re st in a special ty p e of functional bleeding known
as irregular shedding o f the endom etrium .
K ssentiallv, irre g u la r shed d in g shows all th e en d o m etrial changes
w hich ta k e place at th e end of an o vu lato ry cycle an d thus is con­
sidered an ab n o rm al it \ o f tru e m e n stru a tio n . T he en d o m etriu m shrinks,
sheds, in v o lu tes and reg en erates m ore slowly th a n n o rm ally , as clinic­
ally show n by prolonged and excessive m en stru al bleeding. T h ere is
som e evidence th a t th e co n d itio n is due to en docrine im balance, the
exact n a tu re o f w hich has not clearly been established.
Driessen 1,1 w orking in Treub’s la b o ra to ry in A m sterdam was p ro b ­
ably th e first to n otice th e h isto p athological changes in th e en d o ­
m etriu m associated w ith th is ty p e o f m en o rrh ag ia b u t his d escriptions
are vague. C redit for co rrect an d d etailed description is to he given
to P ankow 23 and to K a u fm u n n a n d llo e c k 33. lia n iecki 32 a t Robert
M eyer’s p ath o lo g ic la b o ra to ry in Berlin published th e first large
series o f eases of irre g u la r shed d in g o f the e n d o m etriu m . T h eir ob serv ­
atio n s w ere review ed and su m m arised by Robert M eyer in th e H enke-

* G ra d u a te Fellow of the Belgian Am erican e d u c a tio n a l F o u n d a tio n , Inc. From

the D ep artm en t of O b stetrics and Gynecology. Colum bia I n iv ersity . College of
Physicians and Surgeons, and th e P resb y terian H ospital. \ e w Y ork. New York.
I ( > \ Y o l . I N o . I (.Jnim tir Ih.V»)
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 T h i c r y . Irregular Shedding »('the Kndometrium

L u b arsch te x tb o o k o f p a th o lo g y 1T. Im p o rta n t c o n trib u tio n s w ere s u b ­

se q u e n tly m ade b y A m erican gynecologists who were p a rtic u la rly
concerned w ith th e etiology o f th e disease 1• 2- *• *• * • 20■24• 30• 31.
A lthough irre g u la r shed d in g o f th e e n d o m etriu m was first described
by E u ro p e a n p a th o lo g ists, th e extensive stu d ies were done by
A m erican gynaecologists an d are m o st im p o rta n t.

C L IN IC A L M A T E R IA L

25 cases o f irreg u lar sh ed d in g Mere collected at the P re sb y te ria n

H o sp ital, D e p a rtm e n t o f O b stetrics and G ynecology, C olum bia
U n iv e rsity , N cm- Y ork. N. Y ., o v er a period of 2 Va years (1950 to
J u n e 1953). 22 p resen ted a clear-cu t clinical an d pathologic p ic tu re
a n d Mere re ta in e d for th e p re se n t s tu d y .
Incidence. E x a c t d a ta as to th e over-all incidence of irreg u lar
sh ed d in g are not av ailab le because m ost of th e gynecologists still
perform c u re tta g e or e n d o m etrial b iopsy for m en orrhagia d u rin g th e
bleeding in te rv a l ren d erin g diagnosis im possible. A ccording to the
lite ra tu re , irreg u lar shed d in g re p resen ts 10 to 17 p er cent o f all eases
o f fu n ctio n al m en o rrh ag ia “• 2I- 3I.
Age. The age of our p a tie n ts at the time m enorrhagia Mas first
noticed bv th e m ranges from 24 to 50 w ith an alm ost even d is tr ib u ­
tion from 24 to 40 and a slight decrease past th a t age. T his com pares
favorably M'itli th e findings of othe rs 2- ’■24• 81• 32. Holmstrom a n d
M cLennan ’s p a tie n ts, hoMever, Mere som ew hat y o u n g e r 8. Irregular
shedding is found th ro u g h o u t the whole period of sexual m a tu r ity
M’hcrcas hyperplasia of the e n d o m e triu m has a predilection for both
extrem es of this period.
Race. 5 out of 22 p a tie n ts Mere N egro but no conclusions can be
draM n because b o th p riv a te a n d Mard p a tie n ts are considered in this
s t u d v an d th e racial in cidence for b o th groups is n o t know n.
Gravidity and Rarity. No d ata Mere available for one p atien t. Of
the rem aining 21 patients, 4 had never been pregnant, 7 were primi-
parous and 10 secundiparous. A history of spontaneous abortion M as
reported by 0 out of 21 p atien ts, 3 having had each one abortion and
the three others having had respectively 2, 3 and 5 abortions. In
5 out of 21 patients, the m enorrhagia Mas chronologically connected
M'ith gestation. T mo of them started m enorrhagia im m ediately after
a spontaneous abortion M'ithout curettage. The three other patients
gradually and progressively developed m enorrhagia following a nor-
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 T h i c r y . Irregular Shedding of the Kndomctriuin 3

inal term d eliv ery . Tlie 22 w om en w aited from 1 ' 2 to ” years before
seeking m edical advice, th e len g th of th e delay being usually dependent
upon th e sev erity of th e blood-loss and the involvem ent of general
w ell-being. One p a tie n t co n su lted her do cto r for an in te rc u rre n t
disease in casu a c u te ap p en d icitis. T h ere is no evidence th a t p regnancy
is ctiologically related to irre g u la r sh edding 2- 6- 7 b u t it is strik in g th a t
in one fo u rth of o u r p a tie n ts the m enorrhagia coincided w ith the
first periods follow ing a b o rtio n or p a rtu ritio n . T he sam e o b serv atio n
has been m ad e by o th e rs r>.
Previous H istory. In th e h isto ry of som e of th e p a tie n ts one or more
com m on diseases were found (see tab le). All of th em preceded th e onset
o f irreg u lar shed d in g by at least tw o years w hich fa c t m akes th e ir
etiologic role r a th e r d o u b tfu l. Cases in w hich irreg u lar sh edding was
preceded b y e n d o m etrial h y p erp lasia have been r e p o r te d 2 b u t
th ere is no reason to assum e a com m on etiology. T h ree of o u r p a tie n ts
h ad been u n d er tre a tm e n t for a th y ro id condition. All b u t one (case 4)
had a no rm al basal m etab o lism ra te (BM R) at th e onset of the
m en o rrh ag ia.
TABLE

\ umbe *r N um ber o f years

1)isease of T re a tm e n t to o n set of
patien t irreg u lar shedding

Acute pelvic inflam m atory

disease i C onser\ alive :s
K ndom ctria) by perplasia i C urettage 2
Corpus lu te u m cyst i R em oval i
A ppendicitis :i A ppendectom y 6, 1». 15
B re a s t: benign tu m o r :i M astectom y or 2. 3. H
enucleation
cancer i R adical m astectom y 13
T h y ro id : non-toxic goiter 2 P a rtia l thyroidectom y 2 (case 2). 9
solitary nodules 1 T h yroidectom y 5

Associated Pathology. O ne p a tie n t was suspected of h av in g a chronic

pelvic congestion sy n d ro m e, 3 h ad sm all fibroids on pelvic ex a m in a tio n ,
one p a tie n t p re se n te d a benign cervical polyp, 3 had en d o m etrial
polypi an d one co n su lted for a c u te app en d icitis. T hese associated
p athologic co n d itio n s are in te re stin g and should be considered. Som e
of them (fibroids, e n d o m e tria l polyp) m ay c o n trib u te to th e bleeding.
In th e p a tie n ts checked, th e BM R fell betw een n orm al ranges except
in ease 4. Special a tte n tio n should be paid to blood d y serasias 15 and
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a rte ria l h y p erten sio n as a possible ctiologic fa c to r for th e m e n o rrh a ­

gia. R o u tin e te sts, i. e. w h ite a n d red blood co u n t, leu k o g ram ,
p la te le t c o u n t, p ro th ro m b in level, capillary frag ility te st, bleeding
an d clo ttin g tim e were norm al in th e p a tien ts checked. A systolic
a rte ria l p ressu re h igher th a n 140 n u n . H g was found only in 2 p a tie n ts,
one of whom (case 4) w as know n to h av e essential h y p erten sio n and
was u n d e r tre a tm e n t for this co n d ition.
M enstrual H istory and C linical Sym ptom s. T he sole clinical svm -
pto m in irreg u lar sh ed d in g is g ra d u a lly increasing m en o rrh ag ia w ith ­
o u t strik in g changes in tem po.
It is h a z ard o u s to give s ta n d a rd figures as to w h at should be con­
sidered a n o rm al len g th of cycle an d a norm al period of m en stru al
bleeding. A cycle ranging from 24 to 32 days 12 an d a flow lastin g for
2 to 5 d ay s m ay be considered n o rm al. As these figures v a ry widely
in different wom en but te n d to be ra th e r uniform in the saint* in d i­
v id u a l, we feel th a t d istin c t a n d m ain tain ed changes of an original
p a tte rn should be considered m ore reliable a criterion in judging
m e n stru a l ab n o rm alities. T h ere is no p ractical wav for tin; p atien t to
a c c u ra te ly m easu re th e a m o u n t of blood lost d u rin g a m en stru al
period, hence o u r know ledge is b ased on a p p ro x im atio n . Not all the
p a tie n ts keep m e n stru a l c alen d ars and th eir sta te m e n ts m ust be
accep ted w ith cau tio n .
In 19 in stan ces, th e p a tie n ts re p o rte d th at th e flow had becom e
m ore a b u n d a n t. O ne of th e rem ain ing three was positive th a t her
m enses, a lth o u g h p rolonged, w ere not heavier th an before and th e
o th e r 2 rep o rted a brow nish disch arg e for several da vs a fte r the bleed­
ing was ov er. In all of th e 22 p a tie n ts, th e bleeding period lasted longer
th a n prev io u sly . In 19 it v aried from (> to 13 class and 3 p a tie n ts bled
alm o st th ro u g h o u t th e w hole “ m o n th ” .
T he len g th of th e cycle rem ain ed essentially unchanged alth o u g h
several p a tie n ts p resen ted m inim al tem po v ariatio n s, usually c h a ra c ­
terized as a slight len g th en in g of th e cycle. O ne had com pletely
irreg u lar periods so th a t th e term m enorrhagia can h ard lv be applied
in this case.
As a general rule the len g th en in g o f th e m en stru al period an d the
increase o f th e a m o u n t o f blood lo st coincided and had a g ra d u a l and
progressive ev o lu tio n . H ow ever, in 5 out of 22 cases, m en o rrh ag ia had
a su d d en o n set, one s ta rtin g a fte r a sp o n tan eo u s a b o rtio n w ith o u t
c u re tta g e an d 4 being w ith o u t conn ection to g estatio n . T h e sudden
onset ol irreg u lar shedding post ab o rtio n or p a rtu ritio n has been re­
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p o rted in th e lite ra tu re *• 6 b u t before this diagnosis is m ade, sub-

involution o f th e u te ru s an d re te n tio n of fetal p a rts should be ruled
o u t. O f th e 4 o th e r p a tie n ts re p o rtin g an acu te o n set, 2 had no asso­
ciated p ath o lo g y , one show ed a cystic ovary at culdoscopv (corpus
lulcuni cyst ?) and one had an acu te ap p en d icitis. T h ree o u t of 22
p a tie n ts rep o rted h av in g reg u lar in te rm en stru al episodes o f sp o ttin g
or bleeding.
O ur findings co m p are fav o u ra b ly w ith those of m ost a u th o rs who
report an av erag e length o f bleeding of 7 to 14*, ') to 14 24- **, 9 to
12 7 and 10 to 15 Bd av s. D espite th e u n u su al length o f bleeding '■
th e to ta l length of th e cycle p resen ts only m inim al changes, ./o n e s 31
also observed a fre q u e n t occurrence o f in te rm e n stru a l bleeding in his
series of cases.
K erriprive an em ia is fre q u e n tly associated w ith th is lo n g -stan d in g ,
prolonged an d a b u n d a n t bleeding and m ay affect the general well­
being. (ionsidering a hem oglobin tite r o f 11.5 to 14.5 gm . p er 100 m l.
as n o rm al, only 10 out ot 18 p a tie n ts (4 were n o t checked) had n o r­
mal v a lu e s; 8 ranged b etw een 8.1 and 11.3 gm . In 3 anem ia was
so severe as to req u ire w hole blood replacem ent before c u re tta g e was
done.
T he m enarche occu rred in all p a tie n ts at a norm al age, i. e. betw een
I I and 15 years.
PA TH O LO G Y

No s ta n d a rd d escrip tio n o f th e histological p ictu re c h a ra c teristic of

irreg u lar sh ed d in g ra n be given because (al it changes p ro g ressiv e^
(luring the bleeding p h ase an d (b) various p arts of th e sam e endom e-
l riuin do not show t he sam e p ic tu re at I he sam e tim e. T his coexistence
o f different stages of progression in the sam e m icroscopic area is due
to “ protraction” of th e m en stru al phases w hich are ch aracteristic
for th e disease.
Ih e en d o m e triu m in a tru e (o v u lato ry ) m e n stru a tio n passes suc­
cessively th ro u g h fo u r p h ases:
(1) S h rin k in g is m ain ly d u e to resorption of stro m al edem a and
gives rise to a com p act tissue.
(2) T h e b reak d o w n of th e fu n ctio nal layer in to sm all tissue frag ­
m ents bv th e com bined actio n o f necrosis and in te rs titia l h e m a to m a ta
is followed bv th e u ltim a te “ shedding” of th is lay er. T h e loss of
tissue is com plete a fte r I to 2 d a y s 3 1 '1"’, according to N ovak by the
t bird d a v 1!l.
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(3) T h a t sm all p o rtio n o f th e m ucosa which has been reta in e d a fte r

th e rest o f th e e n d o m e triu m has been cast off, involutes to w ard s p ro ­
liferativ e en d o m etriu m .
(4) Regeneration occurs w hereby the raw surface is g rad u ally
covered w ith surface ep ith eliu m . E p ith elizatio n occurs a b o u t th e 4 th
d a y l!’- 20. T h e “ histologic” m e n stru a tio n is over at th is p o in t and the
en d o m e triu m is readv to s ta rt a new cycle.
T his histologic response is not u n ifo rm th ro u g h o u t th e e n tire en d o ­
m etriu m and this lack o f synchronization gives the en d o m etriu m its
“ p a tc h y ” ap p e a ra n ce l!l.
B asically th e sam e histologic changes tak e place in irreg u lar
shedding. More o v erlap p in g occurs, how ever, because th e e n d o m e tri­
um goes m uch m ore slowly th ro u g h ! th e successive histologic stages
(^p ro tra ctio n ^) . T his resu lts in a g reater v ariety o f histologic
p ic tu re s w hich are various co m b in atio n s of different stages o f p ro ­
gression. D u rin g th e rest of th e cycle a histologic p ictu re consistent
w ith th e d ay of th e cvcle is found and is the reason w hv c u re tta g e
m ust be carefully tim ed to m ak e a diagnosis of irreg u lar sh edding
possible. A c u re tta g e perfo rm ed d u rin g the first 48 hours of bleeding
will pro v id e tissu e id en tical so th a t of norm al m e n stru a tio n . T h e find­
ing on th e 4 th or 5 th d ay o f bleeding, or la te r, of a considerable
am o u n t of e n d o m e triu m w hich has functioned (secretory e x h au sted )
is p ath o g n o m o n ic for irre g u la r shedding. T he g reater p a rt o f th e
covering ep ith eliu m has d isap p eared because th e u p p er p a rt of the
fu n ctio n al layer lias been cast off. Due to th e p ro tra c tio n an d the
n o n -sy n ch ro n izatio n o f th e m e n stru a l phases, th e en d o m etriu m shows
all th e co m b in atio n s of p re m e n stru a l, c o n tra c te d , necrotic, frag m en ted
an d in v o lu tin g e n d o m e triu m . M ucosa obtained at tin' end of the
bleeding shows a shift to w ard s in v o lu tio n and regeneration. E n d o ­
m etriu m o b tain ed a fte r th e bleeding has subsided, i. e., a fte r com ­
plete reg en eratio n , is id en tical to th a t from the norm al p o stm e n stru u m .
It is therefo re essential for th e diagnosis that th e c u re tta g e be p e r­
form ed on th e 4 th d ay or la te r b u t before th e end o f th e bleeding.
A m ore d etailed d escrip tio n of th e pathologic p ictu re will be given
w ith each case re p o rt.
T hese co n sid eratio n s com pel us to raise objection to th e choice of
th e te rm “ irre g u la r sh ed d in g ” *. It is obvious th a t this term has been

* H a n iecki32 called th e d ise a se : “ M enorrhajiie ¡its lolixr vcr/.oj^rrtrr M istoiim ifi

dcs E n d o m e triu m s.“
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chosen 21 to stress th e irregularity o f the shedding b u t, irre g u la rity being

inherent in e n d o m etrial d e sq u a m a tio n , the term is a m ere pleonasm .
I f th e te rm is used to a c c e n tu a te th e irregularity o f the microscopic
p ic tu r e 1-20 th en also o b jectio n is m ade because th is irre g u la rity of
the m icroscopic p ic tu re is only one of th e resu lts of “ p ro tra c tio n ” .
P ro tra c tio n being m ore ty p ical for the disease th a n th e irre g u la rity
of th e p ic tu re , a b ro a d te rm such as “ protracted shedding” is p re ­
ferred. T h e sh ed d in g being b u t one of the histologic ph ases and all
of th e phases being p rolonged, th e term ou g h t to be kept even m ore
general an d a d escrip tiv e te rm as “ menorrhagia due to protracted
(prolonged) m enstruation” seem s m ore correct.

C A SE D E S C R IP T IO N

Case I. A w hite, 30-year-old g ra v id a ii, para ii consulted for th e c o m p lain t of

heavy a n d prolonged m enses. P a s t surgery com prised an ap p en d e cto m y 12 years
ago a n d a radical m aste cto m y for carcinom a 10 y ears ago. T he first m enses appeared
at the age o f 10. U ntil 2 1 >y e ars ago (d a te of the last p a rtu s ) th e m enses had been
reg u lar: cycle 28 days, d u ra tio n of the bleeding 2 to 4 d a y s, a m o u n t no rm al and
slight dysm enorrhoe. Since th e last p a rtu s the m enses progressively becam e a b u n ­
d a n t and longer in d u ra tio n (9 days). T h e cycle rem ained re g u la r a lth o u g h leng­
thened to 33 days. T h e slight dysm enorrhoe persisted and in te rm e n stru a l sp o ttin g
ap p eared . T he last m en stru al period (LM P) was from O ctober 23 to 31. 1952. The
a ctu al period sta rte d N ovem ber 25. 1952 and c u retta g e was done N ovem ber 28.
1952.
T he general e x am in atio n was not revealing. T h e Mood an aly sis show ed a hem o-
globine tite r (Hl>) of I l.l g in .; p la te le t c ount, capillary frag ility te s t and p ro th ro m ­
bin level were norm al. T h e blood pressure (B P ) was I 10 70 m m . Ilg. th e thy ro id
was n o t p alpable and tin* BMR w as norm al. Pelvic e x am in atio n w as essentially
norm al.

iH l rTTTTTTTTTTTTTr rrr rtTTT I ll m l Ml I ll 111 I II I I I

1 5 10 15 20 25 28 , _ _ I
1 5 10 15 20 25 28

l }atholo“ic Report. In stu d y in g th e m icroscopic p re p ara tio n s one sees a large

am o u n t of ty p ical p re m e n stru al e ndom etrium not covered w ith ep ithelium . The
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8 T h i e r y . Irregular Shedding of the Paidometrium

stro m a is ra th e r dense, co n ta in s a m inim al a m o u n t of e x tra ce llu la r fluid a n d con­

sists of sm all ro u n d or oval cells. T he nuclei of th e strom a cells are d a rk , som e of
th em w ith slightly w rinkled m em b ran es and (or) slight pycnosis. T h ey are s u r­
rounded by a sm all c y to p la sm atic rim (P ig. 1). T in y islands of pseudo-decidua cells
are sc a ttere d th ro u g h o u t th e field and grouped som ew hat around th e vessels. These
cells are larger, p olyhedral w ith pale eosinophilic and v esicular nuclei (P ig. 2 and 4).
T he en d o m etrial glands are se rrate d a n d show typical tu ftin g ; th e ir lum ina are
m ostly w ide open a lthough som e are collapsed and sta r-sh ap e d . T he g la n d u la r
ep ith eliu m is o f the secretory e x h au ste d ty p e w ith flat cuboidal cells, a ragged
cellular bo rd er and pale eosinophilic cy to p lasm . The basally located nuclei are
round, pale and vesicular. Secretion is a cc u m u lated in th e lum ina of th e glands
(Pig. I). 'Fhe secretion was identified as glycogen by sta in in g the tissue sections
w ith th e M cM anus periodic acid stain (FA S) and running a control p redigested w ith
p ty alin .
T he coiled arterio les are grouped in so-called a rte rio la r “ fields” (P ig. 2). Most o f
th e lu m in a present v a rious degrees of c o n strictio n in c o n tra st to th e congested
venous sinuses. Special a tte n tio n w as paid to the finer histologic s tru c tu re o f th e
arterio les and for th is purpose, a tric h ro m e Masson, a FA S followed by a control
stain a fte r th e glycogen had been digested by p ty a lin as well as a n orcein sta in were
carried ou t. In ad d itio n VerhoefF’s elastin sta in and L ong’s m odification of the
L aidlaw re ticu lin stain 43* 44 were used for ease 5. Studied b y these special stain in g
techniques, th e en d o m etrial arterioles show some d eg enerative changes. T h e a rte rio ­
lar borders are b lurred. T he tu n ic a a d v e n titia is definitely th in as co m pared w ith
th e p o sto v u la to ry phase and only a sparse am ount of collagen and re ticu lin fibrils
are left. T h e g re a te r p a rt o f th e vessel w all is b u ilt up by th e tu n ic a m edia and is com ­
posed o f 2 to 3 layers o f sm ooth m uscle. Fhe cells have large v esicular nuclei b u t
show no hyalin izatio n . 'Fhe cells o f the tu n ic a in tim a are swollen and th ey p ro tru d e
in to th e lum en of th e vessel (Pig. 3). Most of th e elastin c o n te n t of th e vessel wall
has d isap p eared and only a few tin y fibrils are sc a ttere d th ro u g h o u t the m edia and
a d v e n titia . C oarser fibrils are seen to w a rd s th e periphery b u t no m em b ran a elastiea
in te rn a rem ains (Pig. 4). T h u s th e arterio les disp lay the sam e fibroelastoid d eg en er­
ation as seen at the end of th e n o rm al m en stru a l cycle 36*37*38 w ith the sole difference
th a t th e d eg en erativ e changes are less pronounced th an we w ould h ave expected

Fig, I. Case I. Fhe c u re ttin g s have

the ap p earan ce of ty p ic a l p re m e n ­
strual e n d o m etriu m . T h e en d o m e­
trial g lands are se rrate d a n d some
glycogen is seen filling th e ir lum ina.
No covering epith eliu m is p resen t.
(Ilae m a to x y lin -E o sin . O bj. 16 m m .
oeul. 6 X , green filter.)
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 T h i e r y . Irregular Shedding of the Kndoinetrium

Fig. 3

Fig. 2. Case 1. W ell-developed p seudo-decidual cells are g rouped aro u n d th e a rte rio la r
“ fields” . (T richrom e Masson. O bj. 16 m m ., ocul. 9 X, green filter.)
Fig. 3. Case 1. H igh m agnification of one of the a rte rio la r ’’fields“ seen in Fig. 2.
'Phe tu n ic a a d v e n titia of th e coiled arterioles is th in and o nly sparse a m o u n ts of
collagen and reticu lin fibrils are seen. T he g re ater p art of th e vessel wall is built up
by th e tu n ic a m edia com posed of 2 to 3 lay ers of sm ooth m uscle cells. T h e endothelial
cells are swollen and p ro tru d e into th e lum en o f the vessel. (T rich ro m e Masson.
A pochrom atic obj. Zeiss 4 n u n ., ocul. 9 X , red filter.)
Fig. 4. Case 1. H igh m agnification of one of the a rte rio la r fields seen in Fig. 2. Most
of th e elastic c o n te n t of the vessel w alls has disappeared a n d only a few tin y fibrils
are s c a tte re d th ro u g h o u t th e tu n ic a m edia and a d v e n titia . C oarser fibrils are seen
to w ard s th e perip h ery b u t no m em h ran a elastica in te rn a rem ains. (Orcein stain .
A pochrom atic obj. Zeiss 8 m m ., ocul. 9 X , blue filter.)
Fig. 5. Case 2. S ecretory e n d o m e triu m show ing frag m e n ta tio n a n d early necrosis.
A sm all field o f coiled a rte rio le s is surrounded by b e tte r p re serv e d strom a cells.
(H acm ato x y lin -co sin . O bj. 16 m in., ocul. 9 X, green filter.)
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10 T l i i e r y . Irregular Shedding of the Kndometrium

for this m om ent o f the bleeding phase. T hey are typical of p re m e n stru al endom e­
triu m ra th e r th a n o f th e bleeding phase.
Case 2. A 31-year-old negro w om an, g rav id a ii. para ii. consulted for th e com ­
plaint o f prolonged and heav y m enses. P a st surgerv com prised an appendectom y
(1936) and a p a rtia l th y ro id e cto m y for non-toxic goiter (1949). M enstrual h isto ry :
T he first m enses a p p eared at the age of 15. U ntil 1918 th e cycle had been entirely
norm al and re g u la r: lenght 28 d ay s, d u ra tio n 2 to 3 days, a m o u n t no rm al and no
co m p lain ts of dysm enorrhoe. A brief episode of m cnom etrorrhagia (1919) required
a c u re tta g e (pathologic re p o rt: h y p e rp la sia of th e endom etrium ) and w as followed
by a p regnancy (G ii) and a norm al term delivery (P ii) in J u ly 1950. T he m en stru a l
bleeding grad u ally becam e longer (up to 10 d ay s) and heavier. T he tem po had not
n o tab ly changed (26 to 28 days) and th ere was no com plaint of dysm enorrhoe. T he
UMP w as from 10 to 19 D ecem ber. 1951. T he flow was h eav y and clots were expelled.
T h e a ctu al period s ta rte d J a n u a ry 5. 1952 and a cu retta g e was done on J a n u a ry 10.
1952. T he general physical exam in atio n revealed n o thing abnorm al. T he blood a n a ­
lysis show ed a HI) tite r of 13.2 gin. a n d no indication of blood dyscrasia. T h e B P
w as 1.32 82 nun. H g and the BMR was norm al. Pelvic exam in atio n w as essentially
norm al.

1 5 10 15 20 28 I
1 5 10 15 20 28

Case 2

r V t (h n , ,, ,[
Y 5 l6 ¡5 20 " 'l ' ' 5
5 10 15 20 ,2
i i 8 *
De 7./0 Dec 19 Jon 5 Jon.l0,0
I I

Pathologic Report. T h e histologic p ictu re ( f ig. 5) shows m ore ad v an c ed changes

th an in the previous case. T he stro m a is co n tra cte d and dense and in filtrated w ith
num erous w andering cells and e ry th ro c y te s (in te rstitial h e m a to m a ta ). f r a g m e n t­
a tio n and early necrosis are seen in several fields. The stro m a cells are sm all, have
sc a n ty c ytoplasm and d a rk -stain in g nuclei. Islan d s of b e tte r preserved and larger
cells are seen a ro u n d several coiled arterioles. T he endom etrial glands are secretorv
e x h au ste d . T he lum ina are irreg u lar and filled w ith a sm all am ount o f secretion.
Som e of th e glands show a ten d e n cy to w a rd s collapse. T he arterioles a re in v a rio u s
stages o f c o nstriction and d ila ta tio n , som e being filleil w ith blood. T h eir w alls show
m arked fibroelastoid d eg eneration and alm ost no elastin was d e m o n stra te d w ith
th e orcein stain .
Case 3. A w hite. 30-year-old g ra v id a 0. para 0 with a history of ste rility of u n ­
determ in ed cause consulted for the c o m p la in t of prolonged m en stru a l bleeding.
M enstrual h isto ry : T he first m en stru a l period occurred a t the age of 11. T h e cycle
had been regular (length 28 days, d u ra tio n of bleeding 3 to 1 days, am ount norm al,
no com p lain t o f dysm enorrhoe) un til 7 years ago the m en stru al bleeding gradually
becam e longer but was not m arkedlv m ore profuse. Actually the cycle had a length
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 T h i c r \ . Irregular Shedding of tin* Endometrium

of 30 days, th e bleeding lasted 9 d a y s and the am ount w as w ithin norm al lim its.
T here was no com plaint of dysm enorrhoe. T he LM P was from May 20 to May 20.
1951. T he a c tu a l m en stru a tio n s ta rte d on Ju n e 18. 1951. and a c u re tta g e was done
on Ju n e 25. 1951.
T he general e x am in atio n w as n o t revealing. T he blood analysis show ed a 111)
tite r of 13.5 gm .. the R BC w as 4.5 m illions and no in dication of blood dyscrasia was
found. T he BP was 110-66 m m . Hg. T he BMB w as norm al. Pelvic ex am in atio n
was essentially negative.

(.asc
1 5 10 15 20 25 30 I 5
I 5 .10 15 20 25 30
4
May 2 0
t
May 2 8 June 18
\
June 2 5, D
I

Pathologic Report. T he e n d o m e triu m is c o n tra cte d , frag m en ted a n d there is no

epithelial covering left. T h e stro m a is necrotic and shows pronounced round-cell
infiltration and in te rstitia l h e m a to m a ta (Fig. 6). ’The strom a cells are sm all a n d round
w ith d a rk -stain in g nuclei and very scanty cytoplasm . T h e veins and arterio les are
d ilated and engorged. Several arterio les show throml>osis. T h e e n d o m e tria l glands

Pi". (). Case 3. E n d o m e triu m in a fu rth e r stage o f degeneration th a n in fig. 5. The

stro m a is necrotic and show s pronounced round-cell infiltration and in te rstitia l
h e m a to m a ta . (Ilae m a to x y lin -e o sin . O bj. 16 m m ., ocul. 9 . orange filter.)
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12 T l i i e r y . irregular Shedding of the Kndoinctrium

F ig. 7 Fig. 8

Fig. 7. Case 3. C haracteristic of irreg u lar shedding of the en d o m etriu m is th e g re at

v a ria tio n seen in one and the sam e m icroscopic field. N otice in th e c en ter of th e
field th e slit-like, necro tic gland su rro u n d e d by dense, infiltrated stro m a.
(H aem atoxylin-eosin. O bj. 16 n u n ., ocul. 9 X , orange filter.)
F ig. 8. Case 3. A n a rte rio la r field s u rro u n d e d b y pseudo-decidual cells a n d en d o m etrial
glands. N otice th e perfect p re serv a tio n of the pseudo-decidual cells as com pared
w ith fig. 6 and 7. (T richrom e Masson. A pochrom atic obj. Zeiss 8 m m ., ocul 9 X,
red fdter.)

arc bizarre, sta r-sh ap e d or slit-like in ap p ea ran c e (Fig. 7). Som e of th e glands con­
ta in fossilized secretions in th e ir luinina. T he glan d u lar epithelium is found in
different stages o f in v o lu tio n ; som e are still se c re to ry -ex h a u sted , o th ers are n ecrotic
w ith d a rk -stain in g cy to p lasm a n d p y c n o tic nuclei. Fig. 7 clearly show s th e great
v a ria tio n seen in one and th e sam e m icroscopic field. In th e c en ter of th e field, w here
th e deg en erativ e changes are m ost pro n o u n ced , a slit-like, necrotic gland su rro u n d ed
by dense a n d in filtrated stro m a is seen. Fig. 8 and 9 show an a rte rio la r field at
different m agnifications su rro u n d ed by w ell-preserved pseudo-decidual stro m a
co n tain in g secreto ry glands. T he a rte rio la r walls are m ark ed ly deg en erated w ith
very few collagen and reticulin fibrils left. No elastin was d e m o n stra ted w ith special
sta in s (Fig. 10).
Case 4. A w hite. 42-year-old g ra v id a iv. p a ra ii w ith a histo ry of m aste cto m y for
benign fibroadenom a m am m ae (1946) and essential a rte ria l hyperten sio n (1930)
consulted for th e com p lain t of prolonged and profuse m en stru al bleeding. M enstrual
h isto ry : T he first m en stru a l period occurred at the age of 13. T he cycle w as re g u la r
w ith a d u ra tio n of 28 days. T he m enses lasted 3 to 4 d a y s, were of no rm al a m o u n t
and th ere w as no c o m p lain t of d y sm enorrhoe. Since th e last (said sp o n ta n eo u s)
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 T h i e r y . Irregular Shedding of the Endometrium 13

í ■>».
Fig. 9 Fig. JO

Fig. 9. Case 3. T he coiled arte rio le s are m arkedly d eg en erated a n d th e ir w alls c ontain
only v e ry few collagen a n d reticu lin fibrils. (T richrom e M asson. A pochrom atic
obj. Zeiss 4 m m ., ocul. 9 X . red filter.)
Fig. 10. Case 3. H igher m agnification of p a rt of the a rte rio la r field seen in fig. 9.
No e la stin fibrils are seen in th e w alls of the coiled arterio les. (O rcein stain.
A pochrom atic obj. Zeiss 4 m m ., ocul. 6 X. blue filter.)

ab o rtio n w ith o u t c u re tta g e (1945) m en stru a l bleeding becam e progressively longer

and m ore profuse. A ctually th e cycle had a length of 28 d ay s, th e bleeding w as p ro ­
fuse and of 8 to 9 d a y s’ d u ra tio n , and th ere was co m plaint of slight dvsinenorrhoe.
T he L M P was from May 2 to May 10. 1952. T he actu al p eriod s ta rte d on May 29.
1952, and a com plete abdom inal h y ste rec to m y w ithout oop h o recto m y was perform ed
on J u n e 5. 1952.
T he blood analysis show ed a H b c o n te n t of 11.2 gm .. a RBC o f 3.8 m illions. The

I 5 10 15 20 25 28 I
I 5 10 15 20 25 28

Case 4. II llv ste re c to m v .

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14 T h i c r y . Irregular Shedding of the Kndornetrium

BV1K w as plus 30 per cent and the B P 205 125 min. Hg. Pelvic e x am in atio n was
essentially negative.
Pathologic Report. (H y ste rec to m y specim en.)
M acroscopic: T he u te ru s is grossly n o rm al and contains an endom etrial polyp
a tta c h e d to the fundus.
M icroscopic: T he uterin e c av ity still co n ta in s a considerable am ount of m ucosa.
Som e of th e en d o m etrial g lands are ty p ic a lly star-sh ap ed and su rro u n d ed by dense
in filtrated stro m a, a lth o u g h the g re a te r p art o f th e endom etrium show s in volution.
T h e in v o lu te d glands are stra ig h t and n arro w and glycogen is seen n e ith e r in the
cells nor in the lum ina. T he g lan d u la r epithelium is high colum nar w ith d a rk ,
elongated and basallv located nuclei. An occasional m itotic figure is seen. T he strom a
is som ew hat edem atous and in filtrated w ith round cells. K pithelium ten d s to cover
the surface.
Case 5. A w hite, 39-year-old g ra v id a ii. p a ra ii en ters th e h o sp ital on May 1.
1953, at 1 : 00 P.M . for the c o m p lain t of severe m en stru al hem orrhage. P a st surgery
com prises an ap p en d ecto m y in 1917. M enstrual h isto ry : T h e first m en stru al period
occurred a t th e age of 12. T he cycle h a d alw ays been sh o rt (23 d ay s) b u t regular.
T he m en stru al flow lasted for 7 to 10 d a y s and was of norm al a m o u n t, th e last
d a y s being m ere staining. No dysm en o rrh o e or in te rm e n stru a l bleeding. F o r 1
m o n th s th e flow had g radually becom e m ore a b u n d a n t and at the sam e tim e th e
periods hail lengthened (1 1-15 days). No dysm enorrhoe was noted by the p a tie n t.
T he a c tu a l m en stru al period s ta rte d on A pril 20. 1953. As th e flow w as un u su ally
profuse a n d did not stop b y itself th e p a tie n t entered th e h o sp ital on May 4, 1953.
Pelvic e x am in atio n was essentially negativ e. T h e blood analysis show ed a H b tite r
of 10.3 gm . T h e BP w as 183-80 m m . Hg. P regnancy was excluded and diagnostic
c u re tta g e scheduled for the n e x t m orning. D uring the night (M ay 5) the hem orrhage
becam e so profuse th a t blood tran sfu sio n w as n ecessitated. C u rettag e and to ta l
abdom inal h ysterectom y w ith left salpino-obphorectom y were perform ed the sam e
night.

[ t t H h n ..................i l k * .
I "5 iO ¡5 20 23 I 5 10
1 5 10 15 20 23

Case 5
[ ...... . . . W .. rf - . - - l l > m ..........J — ..........
5 10 15 20 23 )^oy5,D—*- H
*
Apr. 2 0 May 4

Pathologic Report.
Macroscopic ex am in atio n . T h e specim en (uterus, left tu b e and o v ary ) weighs
75 gm . T h e u te ru s m easures 9 X 5 > 5 cm . T he endom etrial c av ity m easures 5 3 cm.
a n d is lined by a th in , red m em brane. T h e m yom etrium a p p ears norm al a n d m ea­
sures 2.5 cm. in thickness. Cervix, left tu b e and ovary are grossly norm al.
Microscopic e x am in atio n . Sections of th e uterin e wall show p art of th e uterin e
cav ity to be lined by a th ic k layer (0.5 cm .) of advanced secretory e n d o m e triu m still
covered (p a rtly ) with surface epithelium (Fig. I I). The stro m a c o n ta in s well deve-
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 T h i e r y , Irregular Shedding of the Endometrium 15

Fig. 11. Case 5. S ections of

th e u terin e w all show p a rt
of th e u terin e c a v ity lined
by a th ic k layer o f advanced
secretory en d o m etriu m still
p a rtly covered w ith surface
epith eliu m . (H a em a to x y lm
eosin.)

loped ascending pillars of p red ccid u al cells surrounding th e coiled arterioles. T he

en d o m etrial g lands are se rrate d and tu fte d ; th e ir lum ina c o n ta in glycogen. T he
g lan d u la r ep ith eliu m is of th e se c re to ry -ex h a u sted type. Special stain in g tech n iq u es
reveal a slight re ta rd a tio n of fibroelastoid degeneration in th e m edial and a d v en ­
titia l lay e rs of the spiral a rte rio le s as no ted and e xtensively described in the previous
cases. T h e m y o m etriu m is n o rm al. No a b n o rm a litie s are no ted in th e cervix, th e left
ov ary or tu b e. T he sam e e n d o m e tria l changes are noted in sections o f the c u rette d
m aterial.

D IS C U S S IO N

In irre g u la r sh ed d in g th e coiled arterioles, w hen follow ed th ro u g h ­

o u t th e bleeding p h ase, show g rad u al fibroelastoid d eg en eratio n . T h e
d eg en erativ e changes are id en tical to those d escribed for the norm al
m e n stru a l cycle, b ein g o n ly m ore delayed in irre g u la r sh ed d in g . T hus
in irre g u la r shedding, th e sp iral arterioles p a rtic ip a te in th e general
process of delayed aging of th e e n d o m etriu m c h a ra c teristic of the
disease. In m a n y p re p a ra tio n s th e arterio lar “ fields” are su rro u n d ed
by so m ew h at m ore slow ly d eg en eratin g stro m a. T his suggests th a t
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th e a rte rio la r “ fields” m a y be re ta in ed a little longer th a n th e rest

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16 I’liii'i y . lrrcjiu la r Shedding o f the Eyndomctriiiiu

of th e en d o m e triu m hut th e arterio les com posing the “ fields” do

d eg en erate n o tw ith sta n d in g th e ir longer reten tio n . T o w ards the end
of th e bleeding phase these “ fields” h ave d isap p eared (have been shed
off) or are very rarely found. T h u s no evidence exists th a t th e a r te ­
rioles are re ta in e d th ro u g h different cycles as suggested by o t h e r s 2".
'Phe well developed a rte rio la r walls reported hv several a u th o r s 1’- 2"
were not found in o u r p re p a ra tio n s.

E T IO L O G Y

Driessen l# im pressed by th e round-cell in filtration seen in irreg u lar

shed d in g - w hich we a c tu a lly know is due to th e lo n g -stan d in g
bleeding - thou g h t th a t th e disease was caused by infection. H e called
it “ en d o m e tritis post m e n stru a tio n e m im p erfectam ” . Pankoiv 25, be­
cause he found no covering e p ith eliu m in the u terin e scrapings of
p a tie n ts w ith irre g u la r sh ed d in g , th o u g h t th a t the disease was due to
th e loss of re g e n e rativ e cap acities of th e en d o m etriu m . Robert M eyer17
was th e first to th in k of a c a u sa tiv e endocrine m echanism , and he
sp ecu lated th a t th e delayed in v o lu tio n and regeneration of th e en d o ­
m etriu m were d u e to o v arian insufficiency. A lthough endocrinologie
e x p la n a tio n s h a v e been fav o red since, it should he rem em bered th a t
local p athologic co n d itio n s (fibroids, subinvolution o f the u te ru s,
e n d o m e tria l polyp, en d o m e tritis post a b o rtu m or post p a rtu m ) m ay
in te rfe re w ith p ro p er d e sq u a m a tio n and su b seq u en t healing o f the
en d o m et rium ,s.
M enstru atio n is believed to he p recip itated bv th e su d d en w ith ­
draw al of th e horm o n al su p p o rt of the en d o m etriu m 26- 2‘- 28- 2il. T he
ag en ts w hich g rad u ally b u ilt up th e secretory u terin e m ucosa suddenly
fail and this failure causes histophysiologic <hanges (sh rinking, sh e d d ­
ing, in v o lu tio n and reg en eratio n ) to occur in th e en d o m etriu m and in
its blood vessels. T h e in tim a te m echanism is still obscure. Som e
a u th o rs tak e it for g ra n te d th a t v ascu lar changes alone can explain
th e p h en o m en a of m e n s tr u a tio n 27- 41. O thers assum e th e existence
o f a toxic agent(s) :i#- •". It is te m p tin g to specu late th a t an
in a d e q u a te w ith d raw al o f th e h orm onal su p p o rt of the en d o m etriu m
(progesterone and estrogens) p re v e n ts these end o m etrial changes. As
b o th horm ones are e la b o ra te d b y th e corpus lu tc u m , in a d e q u a te in ­
v olution of this organ might he cause of in a d e q u a te horm onal
w ith d raw al. Such speculation is p a rtly su p p o rted by’ several
o b serv atio n s b u t, s tra n g e ly , all th e ex p erim ental work has been
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 T h i e r y , Irregular Shedding of the Endometrium 17

focussed upon p ro g estero n e an d no a tte n tio n w h atso ev er has been

paid to a possible role of th e estrogens. On the o th e r h a n d , it is diffi­
cu lt to believe th a t a corpus lu te u m th a t goes on p ro d u cin g sm all
am o u n ts of prog estero n e w ould not produce estrogens a t th e sam e
tim e. M oreover, se c re to ry e n d o m e triu m , as found in irreg u lar sh e d d ­
ing, does n o t exclude th e possib ility of this com bined influence as is
proved b y g esta tio n a l e n d o m e triu m .
H olm strom an d M cL ennan B repro d uced e x p erim en tally b o th th e
clinical an d th e p ath o lo g ic p ic tu re of irregular sh ed d in g in women
w ith a n o rm al m e n stru a l cycle by in jectin g prog estero n e d u rin g the
m enses. I f th e a d m in is tra tio n is s ta rte d du rin g th e p re m e n stru a l phase,
th e effect o b ta in e d d ep en d s u p o n th e dose. Ten ingm . q. o. d. delays
m e n stru a tio n a n d 20 to 30 m gm . q. o. d. p rev en ts it.
M cK elvey an d S a m u e ls 2 recovered sodium pregnanediol-glucuroni-
d a te (V enning’s g ra v im e tric m eth o d 8- 9) in the u rin e o f p a tie n ts w ith
irreg u lar shed d in g d u rin g th e bleeding period. T his is in sh arp con­
tra s t w ith th e n o rm al cycle d u rin g w hich pregnanediol d isap p ears from
the u rin e 1 to 4 d a y s p rio r to m e n stru a tio n l0- 11 a n d rem ain s absent
d u rin g th e bleeding perio d . P reg n an ed ioluria in a h e a lth y w om an is
considered evidence o f a fu n ctio n in g corpus lu teu m . M cK elvey's series
is sm all a n d th e lim ita tio n s o f th e V enning m ethod are know n. N ev er­
theless, M cK elvey's stu d ie s suggest a d elay in th e fu n ctio n al in v o lu ­
tion of th e corpus lu te u m . U rin a ry estrogens and 17-ketosteroids w ere
found b y th ese a u th o rs to be norm al b u t the m eth o d s for u rin a ry
assay o f th e estrogens are too in a c c u rate to p erm it definite conclu­
sions.
Brewer an d Jones 1 s tu d ie d th e corpora lu tea o f p a tie n ts w ith irre­
gular shed d in g an d fo u n d th em grossly n orm al. I t should be noted
th a t th e co in cid en tal findings of a corpus lu teu m cy st in irreg u lar
shed d in g h as been re p o rte d b y o th ers, b u t th e a n a to m ic a l finding of
a corpus lu te u m c y st does n o t a u to m a tic a lly im ply fu n ctio n al h y p e r­
a c tiv ity o f th is o rgan 19. M icroscopically th e co rpora lu te a stu d ied by
Brewer an d Jones h ad n o t u n d erg o n e th e degree of d eg en eratio n con­
sidered n o rm al for th a t p erio d o f th e cycle. It is generally a d m itte d 3-19
th a t it is n o t alw ays e asy to e v a lu a te th e degree o f fu n ctio n al a c tiv ity
of a co rp u s lu te u m from its histologic p ictu re alone because o f th e
v a ria tio n w hich n o rm ally exists in th e m icroscopic a p p earan ce of
co rp o ra lu te a of th e sam e age as well as in various p a rts o f th e sam e
corpus lu teu m . T h e e v a lu a tio n is especially h ard in d eg en eratin g
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corp o ra lu tc a T he lim ita tio n s of th e histologic m ethod som ew hat

w eaken th e a rg u m e n t a d v an ced b y th is careful stu d y .
M en stru atio n due to irre g u la r sh ed d ing is n o t a tru e “ progesterone-
w ith d raw al b leed in g ” . T h e p ic tu re p resented b y th e en d o m etriu m
a fte r th e w ith d raw al of p ro g estero n e does n o t m eet w ith all th e
histologic c rite ria of th is disease 3. W hen g rad u ally decreasing doses
o f pro g estero n e w ere in je c te d in p o stm en o p au sal w om en, w hose u te ri
h a d been u n d e r estrogenic s tim u la tio n , bleeding finally occu rred a fte r
th e dose of pro g estero n e h a d been m ain tain ed a t 50 m gin. q. o. d.
for a period longer th a n th a t req u ired for prog estero n e-w ith d raw al
bleeding to occur 30. T his suggests t h a t th e m enorrhagia of irreg u lar
sh ed d in g is a “ pro g estero n e b re a k -th ro u g h bleeding” ra th e r th a n a
“ p ro g estero n e-w ith d raw al b leed in g ” . T his ex p erim en t fav o rs th e
concept of a corpus lu te u m w hose functional a c tiv ity is m a in ta in e d
a t a low level for several d ay s. It is im possible to assum e a p rim a ry
insufficiency of th e corpus lu te u m w hen one considers th e m arked
secreto ry response of th e e n d o m e triu m in irreg u lar shedding.
I t is n o t know n w h a t p re v e n ts th e corpus lu te u m from und erg o in g
co m p lete regression p rio r to th e o n set o f m en stru al bleeding a lth o u g h
it is obvious th a t th e p itu ita ry sh o uld be considered as a possible
c a u sa tiv e fa c to r. C horionic g o n a d o tro p in , w hich for the m a jo r p a rt
is a lu tein izin g or in te rs titia l cell stim u la tin g horm one, is know n to
p rolong th e life o f th e corpus lu te u m in w om en. T he a d m in istra tio n
o f chorionic g o n ad o tro p in d elay s m e n stru a tio n , an d th u s does not
d u p lic a te th e s itu a tio n en c o u n te re d in irreg u lar shedding. L u teo tro p in
(lactogenic ho rm o n e, p ro lactin ) is also believed to pro lo n g th e fu n c ­
tio n a l life o f th e corpus lu te u m 12• 13’ 14 b u t it has no influence upon
th e le n g th o f th e cycle 3. H olm strom a n d .Jones 3 repro d u ced th e clini­
cal an d th e histologic p ic tu re o f irre g u lar shedding by in jectin g in
n o rm al w om en lu te o tro p in d u rin g th e p rem en stru al phase b u t u n ­
fo rtu n a te ly th e resu lts w ere n o t repro ducible in su b seq u en t p a tie n ts.
T h ere h av e been no in v e stig a tio n s re p o rte d as y e t as to w h e th e r an
incom plete w ith d ra w a l o f lu te o tro p in p rio r to th e onset of bleeding
really occurs in p a tie n ts w ith irre g u la r shedding.
H olm strom a n d Jones 3 th in k th a t th e following endocrine m echanism
m ig h t be responsible for irre g u la r shedding. In co m p lete w ith d raw al
o f lu te o tro p in resu lts in in co m p lete regression of th e corpus lu teu m
an d in in co m p lete w ith d raw al o f p rogesterone. As th e fo rm a tio n of
F S H is th o u g h t to be su p p ressed b y lactogenic h o rm o n e 13, th e rela­
tiv ely high c o n c e n tra tio n o f th e la tte r suppresses th e fu n ctio n of th e
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form er. T h is p re v e n ts th e com plete follicular m a tu ra tio n and a d e ­

q u a te p ro d u ctio n of estrogens d u rin g th e p re m e n stru a l, m en stru al
a n d p o stm e n stru a l p h ases a n d ex p lains th e slow in v o lu tio n a n d re­
g en eratio n of th e e n d o m e triu m . I t is felt th a t th e assu m p tio n of
H olm strom an d Jo n es, h ow ever te m p tin g , com pletely lacks ex p erim en ­
tal proof. W e consider it unw ise to d esignate irreg u lar sh edding as a
d efinite e n tity since th e in tim a te m echanism in volved rem ains u n ­
know n, h u t we agree th a t doing so m ight be useful for th e p ractical
purp o se o f classification.

D IA G N O S IS

A h is to ry of g ra d u a lly increasing m enorrhagia in th e absence of

sy stem ic disease (blood d v serasias, h y p erten sio n ) or organic pelvic
p ath o lo g y (fibroids, e n d o m e tria l polyp, h y p o in v o lu tio n o f th e u te ru s,
re te n tio n o f fe ta l p a rts ) is suggestive o f irreg u lar shedding. Final
diagnosis is e n tire ly based on th e histologic ex a m in a tio n of th e
c u re ttin g s w hich should be o b ta in e d d u rin g th e bleeding period. T h u s
th e diagnosis of irre g u la r sh ed d in g is a clinicopathological diagnosis.
H istologically we find re te n tio n of la te secreto ry en d o m etriu m
u su ally lack in g th e g re a te r p a rt of its covering e p ith eliu m . C om bin­
atio n s o f p re m e n stru a l, c o n tra c te d , frag m en ted a n d in v o lu tin g en d o ­
m e triu m in different m icroscopic fields c o n trib u te to th e w'ild irre ­
g u la rity so c h a ra c te ristic o f th e disease. A scending p illars o f predeci-
dual cells su rro u n d in g th e coiled arterioles are u su ally found. T he
coiled arterio les showr fibroclastoid degeneration b u t th e d eg en erative
changes are less p ro n o u n ced th a n would he expected at th a t m om ent
of th e cycle.
C linically th e p a tie n t com plains of grad u ally an d p rogressively in ­
creasing m e n o rrh a g ia : th e m e n stru a l periods last lo n g er a n d th e flow
is m ore a b u n d a n t th a n before. A sud d en onset o f th e se sy m p to m s is
occasionally found. D esp ite th e u n u su al length of th e bleeding period
th e le n g th of th e cycle p re se n ts only m inim al changes. P a in is not
c h a ra c te ristic o f th e disease an d physical ex am in atio n show s only th e
fre q u e n t associatio n of v a ria b le degrees o f ferrip riv e anem ia. T he
g en italia are essen tially n o rm al.

TH ERA PY

lia lio n a l th e ra p y is im possible as long as the etiology o f irreg u lar

shed d in g is u n k now n. T h u s em p iric m easures are th e sole refuge.
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E v en w ith these th e ra p e u tic m easures experience is lim ited an d th e

o b serv atio n s o f th e resu lts o f th e ra p y listed in th e lite ra tu re are
scarce. A t th e p resen t tim e no single th e ra p y has been sufficiently
tried to allow definite conclusions. In our cases th e ra p y was usually
lim ited to th o ro u g h c u re tta g e o f th e u te ru s, a n d a great m an y of th e
cases w ere seen too recen tly to pro v id e us w ith an a d e q u a te follow -up.
T h e im pression g ained from th e lite ra tu re follows.
A fter co m p lete w ork-up o f th e p a tie n t all associated pathology
should be tre a te d and th e general condition - if necessary - im proved.
Cases of m in o r degrees o f irre g u la r shedding w ith o u t anem ia usually
need no fu rth e r th e ra p y . A g reat m any of the cases are cu red b y th e
d iag n o stic c u re tta g e alone 7• 20- 24• 32 an d here also no fu rth e r th e ra p y
is req u ired . I f th e m en o rrh ag ia p ersists to a degree severe enough
for th e p a tie n t to ask for tre a tm e n t, a second (and ev e n tu a lly a third)
c u re tta g e should be p erform ed before o th e r th e ra p e u tic m easures are
considered. Cases re fra c to ry to re p e ated cu rettag e m ay need m ore
d ra stic th e ra p y alth o u g h th e need for conservatism should be em ­
phasized. In young w om en h y ste re c to m y w ithout oop h o recto m y is
th e o p eratio n o f choice 2- 6- '• 20 b u t in p a tie n ts ap p ro ach in g th e m eno­
p ause X -ra y sterilizatio n is p referred 2• 20. In tra u te rin e insertio n of
rad iu m has not been rep o rted b u t seem s a logic ap p ro ach in older
w om en.
E n docrine th e ra p y has been tried b u t the resu lts rep o rted are not
convincing. H olm strom an d M c L e n n a n 6 use estrogens to stim u la te th e
en d o m etrial grow'th an d to oppose the p ersistent luteal influence by
depressing th e a n te rio r lobe o f th e p itu ita ry . Greenblatt and B a rfield 23
h av e tried m assive doses of in tra v e n o u sly in jected estrogens. T he
injections are rep eated a t b rie f in te rv a ls u n til th e bleeding stops.
T hey should be followed by sm all oral doses to p rev en t “ w ith d raw al
b leed in g ” . T his p rocedure is an em ergency m easure an d therefo re
should only be considered in case of profuse bleeding. T h e h em o static
actio n of high doses of estrogens is well know n alth o u g h its m ech­
anism is d e b a te d . Some a ttr ib u te it to an in h ib ito ry effect on the
o v a ry caused by in h ib itio n of th e p itu ita ry go n ad o tro p in s. O thers
th in k th a t th e con tro l of bleeding is effected b y raising th e circulatory
estrogens abo v e a so-called bleed in g-threshold level. M asters and
M agallon 30 used high doses of progesterone an d th u s c o n v erted the
“ p rogesterone b re a k -th ro u g h b leed in g ” of irreg u lar sh edding in to a
“ p ro g estero n e-w ith d raw al b leed in g ” . The result is a “ horm onal
c u re tta g e ” .
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S u m m a ry

(1) 22 cases of irre g u la r sh ed d in g o f the e n d o m etriu m , collected at

th e P re sb y te ria n H o sp ital, D e p a rtm e n t of O b stetrics an d G ynecology,
C olum bia U n iv ersity , New Y ork, N .Y ., are studied.
(2) T h e clinical d a ta (incidence of th e disease, age an d race of the
p a tie n t, g ra v id ity an d p a rity , p revious h isto ry , associated p ath ology,
m en stru al h isto ry an d clinical sym p tom s) are listed an d discussed.
(3) T h e sole clinical sy m p to m in irregular sh edding is g rad u ally
a n d progressively increasing, painless m enorrhagia w ith o u t strik in g
changes in tem po.
(4) T h e p athologic findings in th e en dom etrium are discussed.
(5) O b jectio n is raised to th e use of th e term “ irreg u lar sh ed d in g ”
a n d a m ore a p p ro p ria te term in o lo g y is discussed.
(6) 5 ty p ic a l case histo ries are rep o rted and d etailed pathologic
descrip tio n s given.
(7) A special stu d y w as m ade o f th e h istopathologic changes of the
en d o m etrial blood vessels. T h e spiral arterioles p a rtic ip a te in the
general process o f d elay ed aging o f th e en d o m etriu m c h a ra c teristic of
the disease. No evidence was found th a t the arterio les are retained
th ro u g h different cycles.
(8) T h e étiologie e x p la n a tio n s of irregular sh edding are reviewed
an d discussed. D efinite im pression is gained th a t th e in tim a te m ech­
anism involved rem ain s u n k n o w n .
(9) D iagnosis and th e ra p y are b rie flv discussed.

'Zusam m enfassung

1. 22 Fälle von « irregular shedding o f the endom etrium » (M enorrha­

gie als Folge v e rz ö g e rter A b sto ß u n g des E n d o m etriu m s) w urden in
der g eb u rtsh ilflic h e n u n d gynäkologischen Klinik d er C olum bia U ni­
v e rs itä t, New Y ork, N. Y ., g esam m elt.
2. Die klinischen D aten (p ro zen tu ales V orkom m en d er K ra n k h e it,
A lter u n d R asse d er P a tie n tin n e n , G ra v id itä t un d P a r itä t, A nam nese,
assoziierte P ath o lo g ie, m en stru elle A nam nese und klinische S y m ­
ptom e) w erden beschrieben und d isk u tie rt.
3. D as einzige w ichtige klinische S ym p to m von «irregular shedding»
ist eine progressiv sich versch lim m ernde, schm erzlose M enorrhagie
ohne n en n en sw erte T e m p o v erän d eru n g en .
4. D ie h isto p ath o lo g isch en B efunde im E n d o m etriu m w erden be­
sprochen.
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22 T h i e r y . Irregular Shedding of the Endometrium

5. E s w erden E in w ä n d e gegen d en A usdruck « irregulär shedding»

erh o b en , u n d eine treffen d ere T erm inologie w ird vorgcschlagen.
6. 5 ty p isc h e K ra n k e n g e sc h ich te n w erden b esprochen, von denen
eine gen au e h isto p ath o lo g isch e B eschreibung gegeben w ird.
7. Spezielle U n te rsu c h u n g e n ü b e r die h isto pathologischen V erän d e­
ru n g en in d en en d o m etriellen B lu tg efäß en w urden d u rc h g e fü h rt. Die
spiralfö rm ig en A rterio len n eh m en Teil am allgem einen P rozeß der
v erzö g erten D egen erieru n g des E n d o m etriu m s, fü r die das « irre g u lä r
sh e d d in g » c h a ra k te ris tisc h ist. E s w u rd en keine A n h a ltsp u n k te d a fü r
gefunden, d a ß die A rterio len län g er als w ährend eines Z yklus im
E n d o m e triu m z u rü c k g e h a lten w erden.
8. D ie L ite ra tu r des ätiologischen M echanism us w ird a n g e fü h rt und
d is k u tie rt. Als Folge des L ite ra tu rs tu d iu m s k o m m t der A u to r zu der
Ü berzeugung, d a ß w ir noch keine k lare E in sich t in dieses P roblem
h ab en .
9. D iagnose u n d T h e ra p ie w erden k u rz d isk u tie rt.

Résumé

1° L a p ré se n te co m m u n ic a tio n e st basée sur l’é tu d e de 22 cas

d ’irregular shedding de l’e n d o m è tre . Ces cas fu ren t étu d iés au Service
de G ynécologie e t d ’O b sté triq u e du P re sb y te ria n H o sp ital, U n iv ersité
C olum bia à N ew Y ork.
2° Les données cliniques (fréquence, âge, race, p a rité , an té c é d en ts,
p athologie gynécologique associée, a n técéd en ts m en stru els, etc.) sont
analysées.
3° Il ré su lte de c e tte é tu d e q u e la sy m p to m ato lo g ie clinique
d 'irregular shedding se lim ite à l’a p p a ritio n progressive de règles
a b o n d a n te s e t prolongées. Il n ’y a p as de phénom ènes d o u lo u reu x et
la ré g u la rité d u cycle ne chan g e pas.
4° S u it la d escrip tio n des a lté ra tio n s histologiques au n iv eau de
l’en d o m ètre.
5° L ’a u te u r critiq u e le term e «irregular shedding» e t d iscu te une
term inologie p lu s ap p ro p riée.
6° C inq o b se rv a tio n s, accom pagnées d ’une descrip tio n h isto ­
p ath o lo g iq u e détaillée, so n t données.
7° Le sy stèm e a rté rie l de l’e n d o m è tre fu t l'o b je t d ’une é tu d e a tte n ­
tiv e. Il en résu lte que les a rtério les spiralées, to u t com m e le reste de
l’e n d o m è tre , p re n n e n t p a r t a u processus de régression re ta rd é e , qui
c a ra c térise le syn d ro m e. L ’idée, selon laquelle ces artério les seraien t
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reten u es d a n s l’en d o m ètre d u ra n t plusieurs cycles m en stru els, ne

sem ble pas ê tre fondée.
8° Nos connaissances se r a p p o rta n t au m cchanism e étiologique du
sy n d ro m e so n t trè s incom plètes.
9° Le d iagnostic différentiel et les m esures th é ra p e u tiq u e s sont
discutées.

Acknowledgments. T he a u th o r wishes to express his a p p rec ia tio n to D r. E arl T.

Engle, D irecto r of the L a b o ra to ry for G ynecologic P athology, College of P hysicians
and Surgeons, Colum bia U n iv e rsity , N ew Y ork. N . Y., who suggested th e presen t
stu d y a n d collected th e m ate ria l. T h e a u th o r is indeb ted to D r. S. II. Gusberg for
perm ission to re p o rt Case 5. a n d to D r. V. E panchin for th e p re p a ra tio n of th e m icro­
photographs.

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M enstruation a n d its D isorders. Ch. T hom as. Springfield 1950. ** Kock. J .: New
E ngl. J . Med. 233, 817, 1945. - 43 Long, M . E.: Amer. .1. A n a t. 31. 159. 1947. -
44 Long. M . E.: S tain T echnol. 23. 69. 1948.

A u th o r’s a d d ress:
Dr. M . Thiery. G ynaecological Clinic o f th e U niversity. P a ste u rd re e f 2,
Ghent (B elgium )

Szendi. It.: Gynucrnlogiii 139. 21. 1955

Aus d er K rau en ab teilu n g des K o m ita tsk ra n k cn h a u se s zu G y u la, U ngarn

(L e ite r: B. Szendi. K a n d id a t d e r mcd. W iss.)

P a ra u re th ra le -p a ra v e s ik a le G eschw ülste

Von B. SZ E N D I

In d er N a c h b a rsc h aft d er w eiblichen U ro g enitalorgane bildet m an

auch solche zy stisch e oder solide G eschw ülste, die g en etisch zu kei­
nem d er a u sg e sta lte te n O rgane des U ro g e n ita la p p a ra tc s gehören,
den n o ch wegen ih re r L age, k linischen und pathologischen Ä ußerungen
und in A n b e tra c h t ih re r B eh an d lu n g m it diesem A p p a ra t Zusam m en­
hängen. D iesen sog. « P a ra tu m o re n » liegen die E n tw ic k lu n g sstö ru n ­
gen d er U ro g en italo rg an e, die p artielle E rh a ltu n g ih rer V orstadien
bzw . K e im stre u u n g z u g ru n d e, welch le tz te re aus d er Vor- u n d U n tiere,
dem W o lff-G artner-M üllerschen G ang, ferner den A nlagen d er K loaka
und des Sin. u ro g en italis ab g e sc h n ü rt w erden. Ih re B esp rech u n g ist
eine w ichtige u n d zeitg em äß e A ufgabe, nicht n u r vom G esich tsp u n k t
der D a te n sa m m lu n g aus, sondern auch d aru m , weil ihre B earb eitu n g
in die B ed eu tu n g d er im L aufe d er O rg anentw icklung v e rstre u te n
em b ry o n alen , atv p isc h e n o d er dvstopischen usw . Zell- u n d Gewebs-
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