The frequency of anovulatory menstruation as determined by endometrial biopsy

THE

FREQUENCY OF ANOVULATORY MENSTRUATION DETERMINED BY ENDOMETRIAL BIOPSY ARTHUR

B. LEVAN, (From

AS

M.D.,* AND PAUL B. SZAKTO, M.D. KANKAKEE, Im. . the Kanlcakee

State

Hospibl)

ORNBR in 1927 was the first to suggest that the anovulatory cycles which he had observed in monkeys might OCCLU in human beings.’ Earlier investigators had reported that, anovulatory bleeding occurred in the monkey, but Corner was the first to have a controlled group of animals with menstrual histories. He found that out of twenty-seven cycles only seven were ovulatory.2s 3 Later Hartman showed that anovulatory cycles could occur in monkeys at any time in the midst of a series of ovulatory cycles ;4 and Bartelmez,s in a review in 1937 cited seventeen satisfactory human casesin which menstruation had occurred at the expected time without either ovary containing a corpus luteum which could be ascribed to the immediately preceding cycle. The endometria, as Corner showed, were nonsecretory in type when anovulatory bleeding occurred, and Robertson, Maddux, and Allen6 demonstrated that uterine bleeding occurred in castrated monkeys following the withdrawal of injections of female sex hormone. Anovulatory bleeding may be expected to be most frequent at the menopause and at puberty, when corpora lutea seldom occur and the Qraafian follicles persist. These phenomena are correlated with the relative sterility of these periods.? The frequency of anovulatory menstruation has been variously estimated. Mazer and ZisermarP reported that twenty out of forty-one sterile women showed anovulatory cycles, whereas Tietzes found that only 7 per cent of his sterility patients showed anovulatory endometria. Lass and his co-workers*” reported that in forty-seven lactatin, w women with previously regular menses, 106 (55 per cent) of 194 cycles were anovulatory. Morton and Hayden found only 7 anovulatory cycles in 142 menstrual periods of thirtythree normal, regular, young women.ll In our work we desired to determine the frequency of anovulatory menstruation in a group of women with previously regular menstrual periods. For our patients we were able t,o secure 103 cooperative women from among the female population of the Kankakee State Hospital. All of these women were psychiatric patients; all had regular menstrual periods. Endometrial biopsies were taken in almost all cases twenty days or more following the last menstrual period. In no case was a biopsy taken when the patient had been menstruating longer than forty-

C

*Now

on

duty

at

the

Brooke

General

Hospital,

75

Fort

Sam

Houston,

Texas.

‘76

AMERICAN

JOURNAL

OF

OBSTETRICS

AND

G~NF.COILJGP

eight hours. In a few instances we were compelled to take biopsies earlier than twenty days after the preceding period. However, in this latter group, when the microscopic examination of the specimen revealed a nonsecretory endometrinm, it was discarded and ihe biopsy repeated at a later date in the same cycle, or in the next cycle. The biopsies were taken from as high in the uterus as possible, two specimens being taken from the anterior wall, and two from the posterior wall as advised by Kotz and Parker.14 All of our biopsy specimens were stained with hematoxylin and eosin. In doubtful. cases Best’s carmine stain fat glycogen, and the thionin &in for mncin were nscld to elucidate t,he diagnosis. In the microscopic interpretation of the specimens, the following criteria were used as indicative of the secretory phase : 1. The presence of secretion, glycogen and mucin, within the lumina of the glands; subnuclear vacuolation was not considered to be a sign of early secretion since it, has been shown t,hat this may occur in castrated monkeys under est.rogen stimulation alone; however, the presence of glycogen in the rest of the cell was taken as a sign of progesterone stimulation;12b I3 2. Characteristic tortuosit,y of the glands, although this was not present in all the specimens diagnosed as being in l-he secretory phase ; 3. Stroma abundant, particularly in the compacta, with relatively large round cells containing a fairly abundant cvtoplasm, and with increasing va.scularity and edema. Since it is of the entire the first and of secretory glands.

likely that some of our biopsies did IKJ~ idL& ii section endometrium and were mainly compa(Q, we relied UpOn third criteria mainly, although in practically e~‘er~’ section Of the cndometrium there was some clqree 01 torluosity

Results We obtained 261 satisfactory biopsies t’r’om 103 women. The pertinent information regarding these patients with anovulation and the results of the microscopic examinations are found in Table I. Tt will be seen that there are 67 women from whom 3 endometrial biopsies each were obtained. Not all of these, however, are from consecutive periods, since at certain times a previously cooperative patient will refuse to submit to examination only to reverse her attitude completely at a latex date. There are also 24 patients with 2 biopsies each, and 13 with 1 biopsy each. Of the 261 specimens only 14 were found to be nonseC&rctory, giving,a percentage of 5.36. (Although various degrees of endometrial development were noted, we have simply classified our findings as either secretory or nonsecretory.) These 14 anovulat.orp cycles occurred in $I or 8.67 per cent of the patients. Two patients showed 3 successive nonsecretory endometria. There was 1 patient with 2 anovulatory cycles out of 3 ; and 6 patients, of whom 5 had 3 biopsies, and one 2 biopsies,

PT.

‘3

_J!‘., N.

G., E.

K.,

s.,

s., P.

w.,

M.,

20

22

38

55

31

67

77

E.

P.

G.

L.

n

M

c

0

0

ij

ij

ij

0

ij

C., M.

9

ON.

NAME

NO.

INCIDENCE

TOTAL IKJMBER ANOVULATORY

33

46:

3ti

43

40

28

..30

67.5

30

AGE

BIOI’SIES ENDOMETRIA

MENTAL

I

nsvchosis --~-.--

li

PATIENTS

deficiency

Dem. precox simple t,ype

Dem. precox hebephrenic

Dem. precox hebephrenie

Dem. preeox hehephrenic

Dem. precox catatonic type

Dem. precox hebephrenic

-.uem. preeox hebephrenic

W:thmt -...--

Mental

OF

type

type

type

type

type

type

DIAGNOSIS

nr~r~Y I”---‘

hebephrenic

nom --e-s

DATA

.5.36yg

‘61 14

?

-1.5a.

4d. Neg.

Cd. Scolioris

3d. Neg.

Id. Neg.

7m

4a. Mild

c:

%I.

MENSES

SHOWING

TABLE

1).

.iNOVI‘I,.i’1OI:Y

I

L.

3. i 0-. 3. 1. 2. :3. 1. 2. ::. 1. 2. 3. 1. 2. 3. I. 2.

2. 3. 1. 2. 3. ;:-

1.

2/16/41 2j17j41 .3/26/41 2/ c ,“T 3j -ii/;,; 3/28/41 ‘> ,z /1L, /1IU,41 3/22/41 4/76/41 12/;6;41 l/20/41 2/26/&l Z/23/41 Z/23/41 4/19/41 l/15/41 3/24/41 4/16/41 2/ 5/41 ::/ l/41 3/26/&l 12/15/41 2/12/-&l 3/13/41 3/l 7/41 4/ 7/41

h4. P.

t’Y(‘I,ES

INCIDENCE

TOTAL NUhfBER PATIENTS WITH

l3.4TE

3. 3. 1. 2. 3. 1. 2.

1.

3/22/41 4/14/41 l/11/41 3/10/41 4/ 4/41 4/ 7/41 5/ 5/41

r/%/41

l/11/41

2/25/41 Y/20/41 2/&5/41 3/18/41 4/21/41 2/24/41 4/14/41 5/ a/41

1.

2/u/41 3/ 5/41 3/27/41 ‘/i) 3/41 3 /24/41 J/21/41 3/ ‘l/41 4/14/41 5./ j/41 2. 3. 1. 2. 3. 1. 2. 3.

1. 2. 3. 1.2. 3. 1. 2. 3.

kS.UPSI

I’ATIESTS ANOVT-LATORY CYCLES

9

2. 3. 1. 2. 3. 1. 2. 3. 1. 2. 3. 1. 2. 3. 1. 1.

1.

1. 2. 3. 1. 2. 3. 1. 2. 3.

Nonsecretory Secretory Secretory Nonsecretory Nonsecretorv NonsecretoriSecretory Secretorv Nonsecrktor~ Secretory Nonsecretor: Secretory Mecertor;v Secretorv Nonsecrktoq Nonsecretor: Secretory Secretory Nonsecretory Nonsecretory Nonsecretory Secretorv Nonsecrkorr Nonsecretor) Secretory Nonsecrctory

Al IC'ROR('OPI('

8.67%

10

DIAG.

78

AMERICAN

JOURNAL

OF

OBSTETRICS

AND

GYNECOLOGY

which each showed one anovulatory cycle. Of the 9 patients showing anovulatory cycles, 4 were nulliparous, and 5 had borne children. Three of the nulllpara were under 40 years of age; 2 of the parous women were under 40 years; 1 nullipara and 3 parous women were past 40 years of age. (Table II.) TABLE

II.

PATIENTS

SHOWING

ANOVULATOEY CYCLES AND PARITY TJNDER 40 YEARS OF AGE 0il 2

PARITY Nulliparous Parous

(~ROUIJED

-

h~~oRnrx;o

w

AGE

40 YEARS OF AGE AND OLDER 1 3

The 2 patients with the 3 successive nonsecretory periods were below 40 years of age. The first was 25 years old, a nullipara wit.h regular menses, and completely normal physically. Her mental diagnosis was “Psychosis With Mental Deficiency. ” The second patient was a 36year-old para ij with regular menses, physically normal with the diagnosis of dementia praecox. The patient with 2 successive anovulatory periods was 46 years old and nulliparous, suffering from dementia The remaining 6 patients were all praecox, and physically normal. patients with dementia praecox with no physical findings. The first was 40 years of age, a para ij ; the second, 35 years of age and also a para ij ; the third was a 2%year-old nullipara ; the fourth a 40-year-old para ij ; the fifth a 43-year-old para ij ; and t,he sixth patient. was a 33-yearold nullipara. From our results it does not appear that parity affects the incidence of anovulation to any sign&ant extent in women who are menstruating regularly. (Table II.) Of 46 nulliparous women, there were 4 who showed one or more anovulatory cycles, giving an incidence of 8.7 per cent; there were 57 parous women, 5 of whom had anovula.tory cycles giving an incidence of 8.77 per cent,. (Table III.) TABLE

111.

GENERAL

I~cmmm

ot' ANOWLATION

X(.CORDING

TO PARITY

Age would seem to influence the frequency of anovulatory menstruation. Of 36 nulliparous women under 40 years of age, 3 had nonsecretory endometria resulting in an incidence of 5.3 per cent; 2 parous women under 40 years of age were found to have anovulatory cycles out of a group of 29, giving an incidence of 6.89 per cent; 10 per cent of the nulliparous patients and 10.7 per cent of the parous patients, over 40 years of age, had anovulatory cycles. (Tables TV and V.) TABLE

IV.

INCIDENCE

AGE GROUP Under 40 years of age 40 years of age and older

OF ANOVLTLATION

(

T;;

IN NULLIPARA

( %::y

ACCORDING

/

TO AGE

“-;y

LEVAN TABLE

V.

AND

INCIDENCE

SZANTO:

ANOVULATORY

OF ANOVULATION

IN PAROW

79

MENSTRUATION WOMEN

ACCORDING

TO AGE

AGE GRoUP Under 40 years of age 40 years of age and older

Comment Our results show that anovulatory menstruation is relatively an infrequent occurrence in regularly menstruating women. In women whose menses are irregular, the frequency would probably be higher. Parity is apparently of little significance; but age is a factor, there being a definite increase in the percentage of anovulatory cycles in women past 40 years of age. If a larger group of women was studied, it might be possible to show a definite percentile increase of anovulatory bleeding in women past 40 years of age with each successive year of life nnt)il the menopause was completed. There is another factor which we must consider, namely, that our patients are all psychotic women. Of the 9 women who menstruated without ovulating, S were schizophrenics, and 1 was a psychotic with mental deficiency. It, is well known that schizophrenic patients often cease menstruatin, ty for variable periods of time after arriving at a.11institution; and also that occasionally shock therapy will halt menses. It is also possible that ot,her disturbances may be more frequent in schizophrenics than other types of patients. Without intending to imply any particular type of personality trend, we note, however, that our incidence of 14 anovulatory cycles in 261 menstrual periods compares quite closely with Morton and Hayden’s incidence of 7 anovulatory cycles in I42 menstrual periods occurring in 33 normal, regular, young women. Our incidence is 5.36 per cent; theirs is 4.9 per cent. It would have been most interesting IO see the effect of gonadotropic hormone upon the endometria of the patients with successive anovulatory cycles, but we were not in the position to carry out this work. Summary 1. Two hundred and sixty-one endometrial biopsies were taken the last, one-t,hird of the menstrual cycle from IO3 patients in a mental hospital. 2. Fourt,een anovulatory cycles were found in 9 patients. Two patients showed successive anovulatory cycles; seven patients showed both anovulatory and ovulatory cycles. 3. Parity was not found to be a factor, but women past 40 years of age were seen to show a higher incidence of anovulatory menstruation7.69 per cent as compared to 10.52 per cent. 4. In this group of patients the incidence of anovulatory cycles was 5.36 per cent. The patient incidence was 5.7 per cent,.

80

AMERICAN

JOURNAL

OF

OBSTETRICS

AND

(;YNECOI,OGT

5. While all the women in this group are psychotic patients, the incidence of anovulatory menstruation in them compares quite closely with that found in normal, healthy women.

Beferences 1. corner, 0. w.: J. A. M. A. 89: 1938, 1927. 2. Heape: Quoted by Corner. 3. 4. 5. 6.

Van Herwerden:

Quoted by Corner. Inst. Wash. Pub. No. 133, 1932. G. W.: Physiol. Rev. 17: 28, 1937. D. C., Maddux, W. P., and Allen, E.: Endocrinology

Hartman, C. G.: Carnegie

Bartelmez, Robertson, 14: 77, 1930. C. G.: Curtis: Obstetrics and Gynecology, Phila7. Novak, E., and Hartman, delphia, 1933, I: 344. 8. Mazer, C., and Ziserman, A. T.: Am. J. Surg. 18: 332, 1932. 9. Tietze, K.: Arch. f. Gyngk. 156: 35, 1933. J., and Kurzrok, R.: Endocrinology 23: 39, 1938. 10. Lass, P. Smelzer, 11. Morton, D. G., and Hayden, C. T.: West. J. Surg. 49: 15, 1941. 1940, W. B. 12. Novak, E.: Gynecological and Obstetrical Pathology, Philadelphia, Saunders Co., Chapt. VII. 13. Cleveland, R.: Endocrinology 28: 388, 1941. Endocrinology 24: 447, 1939. 14. Katz, J., and Parker, E.: