Postmenopausal endometriosis

l’OSTMlI:NOP~~iSl,hll A

h3F:

IRVING

&l’OR’l’ 1,.

ASD

hISK,

the

Gytwcolo,qrlic

&!3TlC\\-

31.1 ).,”

~AML~I~LH. (From

ENI)O;\1l~~TRIOSIX

(:EIBT,

IVartl

(nd

GB’

TIHK

bU!!RATLTRE:

~‘1IIl~.~D~:Iit’tiI;\,

>J.b.,

Lrtbomlory,

NF:\v

I’-\.,

YORK,

Tkf

Aloud

N.

ANI) y.

Sinai

HospilrtlJ

T IS insuficiently emphasized in the literatare on endometriosis that typical lesions are not infrcyucntlp found in women I)ast, the IW110pause. The existence of a sizable grolllJ of noncyclical women lJl’t‘Sellting these lesions deserves consideration, because one might not predict such a group from accepted concept,s ot’ the ljathogenesis of the disease and further, because the origin and t’atr of such tumors aw oi’ WINYWI in prognosis and treatment of’ these IJiLtitXltS. Pathologic diagnos#is ol’ the lesion depends on the demonslratiun (~1 epithelial elements closely resembling endometrium, in an abnormal location. Many thcorics have been ad\anwcl to accolmt for the presence of this ectopic tissue. and, although each seems, to csplain certa.in clinicopathologic observations, bhe accumulated hod\- of evidence cont,ains data irreconcilable with any single theory. This suggests that, no singlr mechanism is universal in the pat,hogt:ncsis of this discasc. Whether. however, one attribnlw the genesis of l-he lwion to (a ) diverticnlar invasion of the uterus b>- normal cntlonrdriam (C’nllen 1, (1)) activation of celomic rests (Iwanofl, Novak), (V i cpithelial hcterotopy dcpcndcnt

I

FRANK

AND

GEIST:

POSTMENOPAUSAL

ENDOMETRIOSIS

653

on inflammatory or hormonal stimulus (Meyer), (d) lymphatic or hematogenous spread (Halban), or (e) retrograde tubal menstruation (Sampson),* it seems logical to concede that its subsequent growth and invasiveness are dependent on the same hormonal influences on which the growth of normal endometrium is contingent. The lesion, as observed in the cyclical woman, is characterized by symptoms indicating cyclical growth activity, and by the histologic pictures of proliferation and edema, desquamation and hemorrhage, closely paralleling the changes of the normally situated endometrium. Moreover, endometriosis before the menarche is exceedingly rare. Not only does hormonal stimulation appear to be necessary for the growth of these tumors, but evidence of hyperestrinism is to be found in a large proportion of these patients, as previous authors have argued.14* I9 In the absence of laboratory data, the evidence on this point rests on the coincidence of endometriosis with endometrial hyperplasia and follicular cysts, lesions which are probably related to hyperestrinism. Uterine fibromyomas, also possibly related to endocrine causes, are, similarly, quite frequently associated. We have reviewed the records of all cases of uterine endometriosis (adenomyosis) surgically treated in this hospital during the nine-andone-half-year period from January, 1933, to July, 1941, with special attention to the age, menstrual status, symptomatology, and associated pathology. An analysis of the associated findings in the 203 cases (Table I) reveals a statistically significant. incidence of the above-mentioned lesions; much in excess of that to be expected were these lesions and cndometriosis etiologically independent. This finding is in qualitative agreement with those of other reviewers (Table II). The above considerations make it reasonable to conclude that the growth and maintenance of ectopic endometrial foci are dependent on hormonal stimuli. Paradoxically, however, these lesions are found in women past the menopause, a state characterized by hypoplasia and atrophy of the genital epitheliums. In this series of 203 cases of adenomyosis, there are found 23 patients in the menopausal group, employing as criteria either amenorrhea for periods in excess of six months, or definite symptoms and signs of the menopausal state. In previously published series of cases, t,he presence or absence of the menopause is not indicated, but, by the arbitrary selection of age 50 as the onset of the menopause, one may obtain a crude estimate of the number of menopausal patients in such series, for purposes of comparison. This would seem to be an acceptable procedure, inasmuch as the number of cyclical patients over that age is commonly much fewer than the number of menopausal patients below that age. In Table III it will be noted t,hat 10.6 per cent of the cases fall into the menopausal group, an incidence much higher than one might expect.

21 158

x 13.0 14.0

74 22.0 i..i 4.5 I5.c 1.5 LO 1 .n 0.5 0.6 11

Parovarian Endometriosis Endometriosis Endometriosis

cyst of pelvic peritoneum of abdominal wound of appendix II.

TABLE

= AUTHOR

Water@ Witherspoon Henderson*3 Jeffcoatel4 Allen1 King15 Smith17 Dreyfussh Bland” Fallas and Counsellers This series

PATHOLOGY

NO.

1 no

172

1::

NO. OF CASES 152

Rosenhlums

-

111.

CO-INCIDENCE L"OLLI('ULAR ('YSTS

Roaenblumj

L)reyfuss"

Total

I

= CASES OF I PERCENTAGE ENDOMETRI-

T.4BLE

Fallas and Bland2 Counsellers This series

ASSOCIATED

:

OSIS IN SERIES 18 44 s! 11:: 17” 114 159 102

AUTHOR

2.5 1.5 0.5 0.5 0.5

5 IIa

Am

USDER 0

DISTRIBUTION

2

FRhKK

AiKD

GEIRT:

POYTMENOPA‘IJS.~L

EiVDOMBTRIOSIS

We have recently encountered a patient classed in this group, have been able to study the case clinically and endocrinologically. CASE

655

and

REPORT

B. V., a 63-year-old white woman, was admitted to Mount Sinai Hospital on Sept. 18, 1941, to the gynecologic service of Dr. S. H. Geist. She complained of aching right lower quadrant pain and backache present during the week prior to admission. Ten months previously she had visited a physician for a similar complaint and was told she had a right ovarian cyst. She remained symptom-free for seven months thereafter, when she had a sudden bout of vaginal bleeding lasting two days. Subsequently she was perfectly well until the present episode. Menses had been entirely normal, without dysmenorrhea or excessive flow. Flow began at the age of 13, occurred every thirty days and lasted for three days. There were three pregnancies with two ‘full-term deliveries. Last menstrual flow occurred in 1931 at age of 53, and during the following three-year period she had mild menopausal symptoms including hot flushes. Physicd Ezaminafion.-Patient was a small white female with graying hair, normal in distribution. Heart and lungs were negative. Breasts were atrophic. Thyroid was unenlarged. Pelvic examination : “Normal introitus. Cervix small, lacerated. Behind and somewhat to the right of the uterus is the lower pole of a soft, elastic, semicystic mass. The adnexa are not distinctly palpable. ” L&oratory Exan&a’tiotL.-Sedimentation rate was twenty-eight minutes (normally over 60 minutes). W7hite blood count was 7300, and hemoglobin 71 per cent. Operatim.-The right broad ligament was, occupied by a plum-sized cyst. This, together with the right tube and ovary, had undergone torsion, and displayed a hemorrhagic, infarcted appearance. The left adnexa were negative, the ovary appearing small, yellowish-white and atrophic. The uterus was slightly enlarged by the presence of a fundal adenomyoma and a small fibromyoma. Pathologic Study.-Examination revealed an infarcted papillary parovarian cyst, with infarcted tube and ovary, on the right side. The left ovary showed atrophy; no active follicles or follicular cysts were present. Fat stain failed to demonstrate lutein tissue. The uterus contained an The endometrium area of adenomyosis (Fig. 1) and a small fibromyoma. consisted of a single layer of cells with no evidence of convolution or glandular activity (Fig. 2). Glycogen stain failed to reveal significant amounts of glycogen. Endocrinologic Xtdy.-VagimZ smear: The individual cells were, on the average, smaller than those seen in smears from cyclical women. Vagkal biopsy: There was moderate layering but no cornification. In some areas the thickness approached that seen in cyclical women, but for the most part the appearance was that of involutional hypoplasia. Golzadotropic hormone studies: Urine extraction and bio-assay for gonadotropin* revealed a titer of at least 4 rat units per day, which is in the postmenopausal range. The ovarian responses were of the character associated with castrate gonadotropin.

656

AMERICAS

JOURNAL

OF

OBSTETRICS

AND

GYNECOLOGY

Iki’st~roytmic ~OIW~LC shcdies: Blood extraction and bio-assay” failed to demonstrate the presence of estrogens in t.he amounts found during the latter half of a menstrual cycle, t,he extract of 30 C.C. of whole blood fa.iling to elicit a threshold response in castrate rats.

Fig.

Fig.

?.-Section

showing

I.--Section

of

endometrium

the

ailenomyomatous

in

a stat?

of

area

l.XO0).

postmenopausal

atrophy

(XtlW).

DISCCHSIOS

In the light of our previously outlined views of the pathophysiology of endometriosis, the sizable groul) of postmenopausal cases demands elucidation. Consistent with these views, the explanation suggests itself that the lesions found represent residua of tumors which had developed during the cyclical period, and thereafter have persisted in

FRANK

AND

C;EIYT

:

POSTMESOI’AUSAL

657

ENDOMETRIOSIS

relative quiescence and regression. It may indeed be that estragonadal, possibly adrenal, sources of estrogenic steroids supply a stimulus permitting continued, decelerated growth. The occasional finding of vaginal mucosa without regressive change’l and the extraction of significant amounts of estrogenic substance from the urine of some women past the menopause” or after castration7 would indicate that the menopausal state is not invariably one of complete estrin deprivation. It may further be reasoned that androgens, which are excreted in increased amounts with the advent of the climacteric,Z’ may possess some estrogenic potency in the human being, although very little in the rodent. In this connection the demonstration of the estrogenic activity of desoxycorticosteronelG is of interestL . In general, however, it is true that estrogens are in very low titer in most menopausal women, and play a questionable role in the metabolism of these tumors. On clinical grounds, the growth activity of the lesions appears to be in abeyance. In none of the 23 cases here cited were there symptoms attributable to the adenomyoma itself; in all cases operation was performed to relieve symptoms due to other pathology (fibroids, prolapsus, etc.). Certainly there is no evidence, either in our studies or in the literature, to indicate that these tumors can originate de novo after the climacteric, or even persist in active, symptom-producing growth. In summation, the present investigation would indicate that, although uterine endometriosis is not infrequently present in the postmenopausal woman, such lesions are to be regarded as in a state of regression and atrophy, incapable of renewed growth adivity. The tumors do not product symptoms, except, conceivably, as a function of position or size attained during the premenopausal period of development.

1. Theories of the origin of endometriosis are reviewed and the pathophysiologic role of estrogen stimulation is discussed. 2. A series of 203 cases of adenomyosis is presented, of which 23 were An additional case is studied and rein women past the climacteric. ported. 3. The origin and fate are discussed.

of

such

tumors in the postmenopausal

woman

REFERENCES 1. 2. 3. 4. 5. (i. 7.

Allen, E.: AK J. OBST. J. Internat. Bland, P. B.: Counueller, V. 8. : AM. J. AX J. Dreyfuss, M. L.: Fallas, R., and Rosenhlum, Frank, R. T.: New York Frank, R. T., Goldberger, Med. 33: 61.5, 1936. 8. Frank, R. T., Salmon, U. 32: 1666. 1935.

& GYNEC. 26: 803, 1933. Coll. Burg. 4: 99, 1941. OBST. & GYNEC. 36: 877, 1938. OBST. & GYNEC. 39: 95, 1940. Ax. J. OBST. & GYNEC. 39: G.: State J. Med. 34: 1, 1934. M. A., and Salmon, U. J.: Proc. J.,

and

Friedman,

R. :

Proc.

Sot.

964, Sot. Exper.

1940. Exper. Biol.

Biol. 6; Med.

65

658

;\MERICbS

J o~~RW.41~

OF

OBSTETRICS

.
GYIUECOLOGT

117. Geist, S. H.: Treatment of ~kncer ant1 dllierl (‘on~litions, New York. IW~, Harper & Bros., Chap. 101. 11. Geist, 8. H., and Salmon, V. J. : :\?.I. .I. Orrw. C GYNW. 38: :i!Jtl. lCJ:i!). Al.: .l. (Yin. Enclcvrincrl. 1: 77;. 12. Hamblen, E. C., Cupler. W. K., :tml Hnptist, 1911. 13. Hendrrsun, I). N.: AU. .J. OBST. Jr GYAX,. 41: CM-, 1941. 1-i. Jeffcoate, T. N. A.: J. Ohst. & Gynarr. Brit. Emp. 41: M-C, l!U4. 15. King, J. E.: AM. 3. OBST. & GPSEC. 26: %Z, 19X:. 16. Salmon, 11. J. : Proc. Sot. Exper. Biol. Cy- Med. 41: .T 1.:. 19.30. AM. .T. OBST. B GY’NEC~. 17: 8Oti, .lZO. 17. Smith, G. IT.: Virginia ill. Monthly 68: 92, l!Ul. 18. Waters, E. G.: 19. Witherspoon, J. ‘I’.: Arch. Path. 20: 2, 19333. 20. Witherspoon, J. ‘I’.: Surg., Gynec. R- Olwt. 61: 743. 1925.

ROBERT

B.

(:REENBL~~TT, RICHARD

b2.11.. TORPIN,

I”R.ZSK Tv~TAR.\, N.D., .\;un

R4.1).,

AIJGTXT~\,

(:a.

M

ANS- of the neuroses and ills oi’ womenfolk may h tmd to ~111. happy or unsatisfactory scxu:11 relations. The wife wit,hout sexual desire, unless she has histrionic abilit.>- 01’ other c~harms, frequently finds her marital relations strained. So frequently i.he complaint of frigidit; is dismissed by the physician as unwori.hy of consideration or as a condition about which nothing can he done. P’rigidity may be absolute: it may be relative. When frigidity is relative. desire is present but coitus does not culminate in complete gratification. E’rigidity may be due to psychogenic or anatomic factors with resultant dyspareunia or vaginismus. The need for a betker understanding of this problem cannot be questioned. The medical complexities and the social implications The successful treatment of frigidity may circumvent, t 11~ are many. disintegration of a marital union or prevent, a man’s search of extr+ marital adventure with its dangerous consequences. The literatllrc~ is almost void of contributions t,o t,ht* subject. Libido is ‘4 highly complex fun&ion in which psychologic, anatomic*. neurologic, sentiment,al and hormonal components play important roles. The role of the hormonal component has not, received due attention. Tht* experience gained by our group in evaluating the effects of pellets of testosterone propionate implant,ed in over 55 women and pellets of pure crystalline progesterone implanted in 16 \\otrlen lead us to believe that love, libido, and marital harmony arc f’requentlp closely ussociatctl. At *Read Talladega,

by the senior author Alabama, December

at a meeting 16. 1941.

ol’ the

Talladega

County

Medical

Socirty.