SOME POINTS of CONTACT BETWEEN ENDOCKINOLOGY and GYNECOLOGY Emil Novak, Baltimore, Md

SOME POINTS OF CONTACT BETWEEN ENDOCKINOLOGY AND GYNECOLOGY Emil Novak, Baltimore, Md.

(From the Gynecological Department of the Johns Hopkins University.) Many gynecological patients present, as incidental points of interest, endocrine disturbances of one form or another. In some, however, the endocrinopathy dominates the picture, both etiologically and symp- tomatically. This is particularly true of certain types of menstrual disorder which are mere manifestations of internal secretory disturbances. It is with this group of cases, in which gynecology and endocrinology seem to come into closest contact, that we shall deal in this paper. The two great functions of the female generative organs, reproduction and menstruation, are both pro- foundly influenced by disorders of the ductless glands. This is especially true of the menstrual function. It is now definitely known that the cause of menstruation is an internal secretion of the ovary, and that the element of the ovary which is concerned in the process is almost certainly the corpus luteum. The menstrual function is thus brought into the most direct relationship with the ductless gland apparatus. Although the ovary is commonly spoken of as the cause of menstruation, it would seem to be important to emphasize the fact that it is merely the portal—the point of contact—through which the entire endocrine system exerts its influence upon the generative organs. Amenorrhea—The majority of menstrual disorders are, of course, due to one form or another of anatom-

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Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 NOVAK 439 ical lesion in the uterus or adnexa. A certain group, however, is undoubtedly the result of internal secretory disturbance. The most clearly denned type of menstrual disorder which is undoubtedly of endocrine origin is that observed in connection with the well known adiposo-genital dystrophy, or Froehlich's syndrome. The principal characteristics of this syndrome are adiposity and sexual hypoplasia, the latter characterized in women by the occurrence of amenorrhea. This association of symptoms is en- countered with great frequency by every gynecologist. Even in the early days of gynecology, the fact was well recognized that scanty menstruation or amenorrhea is often noted in patients who have taken on a great deal of weight. Instead of explaining the amenorrhea as being caused by the adiposity, or vice versa, we now know, thanks to the researches of Cushing and others, that both are manifestations of the same underlying cause—hypopituitarism. The adiposo-genital syndrome furnishes a striking example of the intimate relationship existing between the various links of the endocrine chain. At first thought, one does not associate the pituitary body with the menstrual function, or look upon hypopituitarism as a cause of amenorrhea. Since the immediate cause of menstruation is the ovarian hormone, it is obvious that the effect of hypopituitarism must be exerted through the medium of the ovary. To be more explicit, if perhaps somewhat theoretical, it would seem that hypopituitarism entails a deficient activity of the corpus luteum—in other words, that under normal conditions the two secretions are syner- gistic. If this conception were correct, one might be justified in assuming that the pituitary is the acti-

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 440 ENDOCRINOLOGY AND GYNECOLOGY vator of the ovarian secretion, and in this indirect way influences menstruation. And yet there is evidence that the mechanism of the amenorrhea observed in this group of cases is quite different. A recent case of my own, unique in my experience, offers evidence that even during the amenorrhea of Proehlich's syndrome, ovulation still takes place, and that corpora lutea are therefore being formed. A young white woman of nineteen, married, was re- ferred to me by Dr. B. S. Hanna, because of amenorrhea of five months' duration. She had gained thirty-seven pounds in weight during the past year. Examination of the pelvic organs showed the uterus to be small in size and normal in position, there being no evidence of pregnancy. The amenorrhea having persisted in spite of treatment by thyroid and ovarian extracts, the patient returned for examination three months later. At this time, eight months after the last menstrual period, the uterus was found to be enlarged to the size of a two and a half months pregnancy. In other words, the patient had become pregnant during the continuity of the amenorrhea associated with her adisposo-genital dystrophy. The occurrence of the pregnancy is, of course, absolute proof that ovulation had taken place —in other words, that corpora lutea had been formed in the ovary. In spite of the presence of the latter, however, menstruation had not occurred. It would seem that the corpus luteum hormone in this condition was either neutralized or antagonized by some other endocrine element, probably of pituitary origin. This phenomenon is analogous to the occurrence of amenorrhea in the lactating woman. It is a well known fact that pregnancy, and therefore ovulation

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 NOVAK 441 and corpus luteum formation, frequently occurs in nursing women. In these cases, the corpus luteum hormone is either inhibited or neutralized by the internal secretion of the lactating breast. Uterine Bleeding—Excessive uterine bleeding, in the form of either menorrhagia or metrorrhagia, is almost always due to one or another of the numerous pathologic conditions which may occur in the uterus or adnexa—retained products of conception, cancer, myoma, polypi, salpingitis, ovarian neoplasms, etc. In a certain proportion of cases, much more frequently than was formerly believed, such bleeding may be observed in the entire absence of any demon- strable pelvic disease. It is suggestive that such functional uterine hemorrhage, as it is called, is noted most frequently at puberty or at the menopause, when endocrine equilibrium is most unstable. The awaken- ing of ovarian activity at the pubertal epoch, and its cessation at the climacterium, .may well be expected to disturb the delicate endocrine balance which spells normality. Menstrual disorders, including uterine bleeding, are often observed-in connection with derangements in the function of the thyroid. There has been some discussion as to whether excessive menstruation is more likely to be associated with hyper- or hypo-thyroidism. My own experience leads me to believe that, while either association is possible, it is with deficient thyroid function that we are more likely to encounter uterine hemorrhage. Hertoghe (1) and Sehrt (2) both hold to this view, the latter reporting that in a series of fifty-five cases of functional hemorrhage he found thirty-eight with definite indications of hypo- thyroidism. As a matter of fact it is probable that

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 442 ENDOCRINOLOGY AND GYNECOLOGY excessive menstrual hemorrhage may be observed with either type of quantitative disorder of thyroid function. There can be little doubt that other elements in the endocrine chain—the pituitary, thymus, suprarenal, etc.—may at times be responsible for uterine bleeding and other menstrual disorders, but our knowledge on these points is so imperfect that it is scarcely profitable to do more than allude to them. Prom a theoretical point of view the form of endocrine disorder which one would naturally think of as most likely to cause uterine hemorrhage would be over-function of the ovary, or hyperoophorism. Al- though such a condition may undoubtedly exist, its study presents many difficulties. In the first place, it is open to question whether we can produce hy- perob'pherism experimentally, although this possi- bility has been claimed by Adler (3). The latter, by feeding ovarian extract to a girl of twenty-one, whose menstruation had always been normal and very regu- lar, claims to have brought on the menstrual period, for the first time in the girl's life, four days before the expected date, the amount, and duration being also much greater than normal. The same observer has studied the problem from an altogether different angle, by means of the reactions of the sympathetic nervous system to various drugs, according to the method first worked out by Eppinger and Hess (4). His conclusions are that over-function of the ovary is the cause of functional uterine bleeding. As I pointed out in a previous paper (5), however, Adler's results are open to serious question, inasmuch as his methods of study seem to take no account of the fact that the

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 NOVAK 443 ovary is only one of the endocrine organs contribut- ing to the menstrual impulse. Although the ovary is no doubt the immediate cause of menstruation, we must not overlook the fact that it is, after all, only one element in the rather complex menstrual machinery. It is commonly conceded that the ovary is responsible for the marked pelvic and uterine hyperemia which is so striking a feature of menstruation. No matter how extreme such a hyperemia might be, it would not in itself explain such a wholesale exodus of blood elements from the endo- metrial vessels as is observed during this process. Inflammatory hyperemia may be far more marked than the physiological congestion of menstruation, but it is rarely associated with any great degree of hemorrhage. In other words, we must assume that during menstruation there is some local factor in the endometrium which increases the permeability of the blood vessels, upon which it appears to exert a more or less selective action. The work of Schickele (6) and others indicates that this local factor, whether it be a hormone or enzyme, is formed as a result of ovarian activity, being apparently a by-effect of the ovarian hormone. Here, then, is another point of contact between the endocrine apparatus and the reproductive apparatus. Dysmenorrhea—The occurrence of dysmenorrhea as a result of endocrine disorders is certainly much less frequent and much more difficult of demonstra- tion than that of either amenorrhea or excessive menstruation. As a matter of fact, only one example suggests itself, and in that the relationship is somewhat indirect. Spasmodic dysmenorrhea is ex- tremely common in young multiparous women, and

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 444 ENDOCRINOLOGY AND GYNECOLOGY is the cause of much suffering and invalidism. The underlying condition in these cases is a greater or less degree of uterine hypoplasia, of the foetal, infan- tile or subpubescent type, according to the classifica- tion which I suggested in a recent paper on the subject (7). It is far more frequent to observe dysmenorrhea in the mild degrees of uterine hypoplasia— the subpubescent group—than in the more extreme forms, such as the uterus foetalis or rudimentarius. In the latter variety, amenorrhea is the predominat- ing gynecological symptom. When dysmenorrhea is observed in young unmarried women with under- developed uteri, the symptom is brought into relationship with the endocrine apparatus by virtue of the fact that disorders of the latter are unquestionably to blame for the uterine hypoplasia, and indirectly, for the dysmenorrhea. Knowledge of this fact should point the way to future efforts to find a satisfactory treatment for this condition. Certainly no one can deny that the results of present-day treatment of this syndrome— whether by drugs, simple dilatation, the use of stem pessaries, or the performance of plastic operations on the cervix—are such as to provoke little enthusiasm among gynecologists. It is true that the same state- ment applies even more forcefully to organotherapy in such cases; but the fault lies not so much with the general logic of such treatment as with the still nebular nature of our knowledge concerning endocrine relationships, as well as the methods of prep- aration of gland extracts. Sterility—Much of what has just been said concerning dysmenorrhea applies also to the discussion of at least one type of sterility—that associated with

Downloaded from https://academic.oup.com/endo/article-abstract/2/4/438/2771059 by Serials Department, Oregon Health & Science University user on 20 March 2018 NOVAK 445 uterine hypoplasia. It is quite possible that our helplessness in this, one of the big problems of gynecology, is due to the fact that we have paid too much attention to the study of mere anatomic defects in the reproductive organs, and too little to the possibilities of a perverted physiology of the generative apparatus. Although I shall not enter into the discussion of this subject, there is much reason to believe that sterility in this group of cases is due to a physiological defect in the endometrium—the absence of some factor, whether hormone or enzyme, which is essen- tial to the implantation of the fecundated ovum. Or- ganotherapy offers nothing as yet in the treatment of such cases, but I firmly believe that the time will soon come when those cases of sterility which are of endocrine origin will be successfully treated by appro- priate organotherapeutic measures. In this brief review I have indicated, in a super- ficial way, only a few of the more important points at which endocrinology arid gynecology come into more or less intimate contact. The field of endocrinology is the whole living body—that of gynecology, as of other specialized branches of medical or surgical science, is often confined to a special region. And that is just the point upon which I would like to put a final emphasis—that the gynecologist whose range of vision is so limited as not to extend beyond the ileo-pectineal line will not only miss much of the fas- cination he might otherwise find in his work, but that, encircling himself with such a narrow horizon, mis- interpret or perhaps overlook clinical manifestations which are at times veritable signboards as to thera- peutics.

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BIBLIOGRAPHY 1. Hertoghe (E.) Thyroid insufficiency. Practitioner (Lon- don) 1915, 94, 26-69. 2. Sehrt (E.) Zur thyreogenen Actiologie des hamorr- hagisehen Metropathien. Miinchen. med. "Wochenschr, 1913, 60, 961-964. 3. Adler (L.) Zur Physiologie und Pathologie der Ovarial- funktion. Arch. f. Gynak. (Berl.), 1911, 95, 349-424. 4. Eppinger und Hess. Sainml. klin. Abhandl. iiber Path, und Therap. des Stoffweehsels, Berlin, 1910. 5. Novak (E.) The pathological physiology of uterine bleeding. Jour. A. M. A. (Chgo.), 1914, 63, 617-621. 6. Schickele (G.) Beitrage zur Physiologie und Pathologie der Ovarien. Arch. f. Gynak (Berlin), 1912, 97, 409-473. 7. Novak (E.) Infantilism and other hypoplastic conditions of the uterus. Jour. A. M. A. (Chgo.), 1918, 71, 1101-1107.

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