THE EOLE OF THE ENDOCRINE GLANDS IN CERTAIN MENSTRUAL DISORDERS WITH SPECIAL REFERENCE TO PRIMARY DYSMENORRHOEA AND FUNCTIONAL UTERINE BLEEDING* Emil Novak, Baltimore, Md. (From the Gynecological Department of Johns Hopkins University) Speaking generally, • the importance of the hormone asso- ciations of an organ or of a body function varies with the de- gree of its automaticity. The highly volitional functions, such as the skeletal muscular movements, are under the control of the rapidly acting nerve mechanism, while the auxiliary influence of the endocrine apparatus is relatively slight. "With the more primitive vegetative functions the reverse is true, for here the mechanism is usually essentially of the endocrine type, with a greater or less degree of contributory regulating influence on the part of the sympathetic nervous system. Menstruation is a function which may certainly be classed as vegetative, and hence it is not surprising that tne explanation of its mechanism is to be sought chiefly in a study of the func- tions of certain endocrine glands, and that the cause of menstrual disorders is not infrequently to be found in disorders of these structures. That there is, even in the case of menstruation, some association with the higher centers, is shown by the occasional occurrence of menstrual aberrations under the influence of pro- found psychic disturbances—the amenorrhea which is often seen in women who dread pregnancy, or in those with an intense longing for it; the occurrence of either amenorrhea or excessive menstruation as a result of sudden shock or fright, etc. For nearly a hundred years, the ovary has been looked upon as essential to menstruation, but no attempt was made to explain the manner in which its influence is exerted, until the formula- tion of the well-known theory of Pflueger, in 1865. According to the latter, menstruation was explained as the result of a pel- vic hyperemia induced reflexly by the pressure of a growing *Read before the Association for the Study of Internal Secretions, New Orleans, April 26, 1920. 411 Downloaded from https://academic.oup.com/endo/article-abstract/4/3/411/2771500 by UB Frankfurt/Main user on 03 April 2018 412 ENDOCRINE GLANDS-MENSTRUAL DISORDERS Graafian follicle on the ovarian nerve terminations. This the- ory was quite universally accepted until it was disproved by the experimental work of Knauer, Marshall and others. These in- vestigators showed that removal of the ovaries, thereby severing all their nerve connections, does not cause cessation of menstrua- tion, provided that the ovaries be transplanted elsewhere into the body. In other words, the ovarian influence is exerted through the blood-stream and not through the nerves, i. e., it is of endo- crine nature. The next step was to determine which of the constituents of the ovary is responsible for the menstrual function. Is it the stroma, the follicles, or the corpus luteum? Without going into detail, suffice it to say that the weight of evidence is overwhelm- ingly in favor of the view that it is the corpus luteum which plays the most important role in this connection. It seems almost as certain, however, that the ovary produces more than one hor- mone. MarafLon, for example, believes that the ovarian hormones may be divided into three groups: One, the genital, has to do with the menstrual cycle; a second, the sexual, with the morpho- logical sex characteristics and a third, the general, assists in all the body functions. The internal secretion of the ovary is closely interrelated with that of other endocrine glands, especially the thyroid, pitui- tary and suprarenal bodies. These relations are not easily de- fined in the present state of our knowledge, but their existence is demonstrated by the frequent influence exerted on menstrua- tion by disease of any of them. Many interesting examples of these relationships suggest themselves for discussion—the role played by the ovaries in the development of the secondary sex characters; the effects of castration at various ages; the rare oc- currence of female eunuchoidism; the relation between menstrua- tion and ovulation, and between menstruation and lactation; the influence on menstruation of the thyroid, pituitary and supra- renal bodies, etc. For the purpose of this brief paper, however, it has seemed more profitable to limit myself to the discussion of two or three of the less obvious relations of the endocrine struc- tures to disorders of menstruation. First of all, I may pass with mere mention that form of amenorrhea now generally recognized as being due to hypopitui- tarism, and which, clinically, is commonly associated with obesity. Downloaded from https://academic.oup.com/endo/article-abstract/4/3/411/2771500 by UB Frankfurt/Main user on 03 April 2018 NOVAK 41:5 Frohlich's report, in 1901, of the first case of adiposo-genital dys- trophy, gave rise to much experimental work, which yielded re- sults long since incorporated into clinical practice. Much has been written concerning the amenorrhea which is found in con- nection with hypopituitarism, and I shall not elaborate on the subject here. • The two menstrual disorders to which I wish to call especial attention, as regards their probable endocrine etiology, are (1) primary or spasmodic dysmenorrhea and (2) uterine hemor- rhage of the type commonly spoken of as "idiopathic" or "func- tional. '' Primary Dysmenorrhea. At first thought there would seem to be little connection between primary dysmenorrhea and the endocrine system, and yet I believe that an important relation of this sort, does exist. By primary dysmenorrhea we mean that form of menstrual pain which occurs in the entire absence of discoverable disease in the pelvis. It is observed with great fre- quency in young nulliparous women, either single or married, and, in the aggregate, is the cause of a vast amount of suffering. The factors which have been considered instrumental in the causation of this form of dysmenorrhea may be summarized as follows. 1. Mechanical obstructions of the uterine canal. For many years after the publication of the work of Mackintosh in 1832, the view was held that spasmodic dysmenorrhea is always due to mechanical obstruction to the exit of menstrual blood from the uterus. Most commonly, it was assumed, the obstruction is due to anteflexion of the uterus. According to this view, the colicky pain so characteristic of the condition is due to spasmodic con- tractile efforts on the part of the uterine muscle. This concep- tion is still quite prevalent among medical men, although the evidence is clearly against its correctness. For example, primary dysmenorrhea often occurs in the entire absence of anteflexion or of other obstructive lesions, and, on the other hand, it is not uncommon to find even very sharp anteflexions in women who suffer no dysmenorrhea whatsoever. 2. Neurotic factor. Aside from the actual hysterical cases, the importance of this factor lies in the fact that it increases the susceptibility to pain, and thus causes a magnification into actual Downloaded from https://academic.oup.com/endo/article-abstract/4/3/411/2771500 by UB Frankfurt/Main user on 03 April 2018 414 ENDOCRINE GLANDS-MENSTRUAL DISORDERS pain of the menstrual discomfort normally experienced by many women. 3. Hypoplasia of the uterus. There is little doubt that by far the most important factor in the etiology of spasmodic dysr menorrhea is defective development of the uterus. It is extreme- ly common to find a greater or less degree of genital hypoplasia in women whose development otherwise is quite normal. These cases of uterine hypoplasia may be classified under three heads, according to the degree of hypoplasia. (a) In the fetal type, the arrested development occurs at a very early stage, so that the uterus resembles that of the fetus. The special characteristics are the small size of the uterus and the fact that it is made up almost entirely of cervix, the corpus uteri being exceedingly rudimentary, (b) In the infantile type, the uterus resembles that normally found in infants and young children. Here again the cervix predominates over the corpus, although the latter is not as rudimentary as in the fetal type. The uterus as a whole is larger and there is often an associated anteflexion, most commonly of the cervico-corporeal variety, (c) In the subpu- bescent type, the hypoplasia is relatively slight. Here, also, there is not infrequently an associated anteflexion. For a fuller discussion of these varieties of uterine hypoplasia and of their clinical significance, I would refer to a previous paper which I have published on the subject. The pertinence of the question of uterine hypoplasia in con- nection with the present discussion rests on two factors: first, that an extremely frequent symptom of uterine hypoplasia, though not by any means a constant one, is primary or spasmodic dysmenorrhea; secondly, that the underlying cause of the various grades of uterine hypoplasia is undoubtedly of endocrine nature. In searching for a cause for the hypoplasia, we at once make contact with the endocrine apparatus in the body. Which of the endocrine glands is responsible for the defective development of the uterus noted in these cases ? In the first place, does the ovary exert any important influence on the development of the uterus before the age of puberty, that is, during the fetal and infantile periods of life? Certainly no such influence can be assigned to the corpora lutea, for the latter do not appear before the age of puberty. The possibility suggests itself that some other element of the ovary may possess this function, but the evidence is not Downloaded from https://academic.oup.com/endo/article-abstract/4/3/411/2771500 by UB Frankfurt/Main user on 03 April 2018 NOVAK 415 convincing.