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The human fetus in utero under normal environmental conditions is said to be in a state of apnea. Oxygenation of the blood is carried on by the placental circulation, so that theoretically intrauterine respiration could serve no useful purpose. It is the popular belief that, under the abnormal conditions which result in an inadequate oxygen saturation of the fetal blood, premature attempts at breathing ensue. Thus, abruptio placentae or cord entanglements may interfere with the oxygen supply to the fetus sufficiently to stimulate the latent respiratory mechanism and induce attempts at intrauterine respiration. Respiratory movements of the fetus within the uterus have been observed and described many times. Ahlfeld. 1 in 1888 was the first to call attention to the rhythmic movements of the fetus in the uterus near term. These movements involved the thoracic cage and were respiratory in character. Reifferscheid 2 confirmed these observations, but both authors felt

R ICHARDSON (i) defines functional bleeding as that which appears in the absence of gross lesions at unexpected times or in abnormal amounts. The cause is unknown, but it is believed to be due to a dysfunction of one or more of the ovarian or pituitary hormones. It is an extremely bothersome syndrome both to the patient and to the physician. Its frequency and widespread occurrence are well known, and it is therefore of definite interest not only to the gynecologist and endocrinologist, but also to the general practitioner, internist and surgeon. Its etiologic factors are obscure and the contribu' tions of the experimental laboratory to its pathogene' sis have been meager. No true pathological bleeding has been produced experimentally, although many menstrual and pseudomenstrual bleedings have been induced with hormonal agents both in woman and monkey (a). Functional bleeding may occur from any type of endometrium, cystic and hyperplastic, proliferative, progestational or atrophic. Experimentally, neither the pituitary nor the ovary is essential for uterine bleeding, and Kurzxok (3) believes the responsible factors reside in the endometrium. Up to recent times, the estrogen withdrawal theory or aberrant estrogenic function has been the basis of all etiological theories. However, it does not explain the bleeding that is clinically noted when con' tinuous large doses of estrogen are given. Also the cystic glandular hyperplasia type, which constitutes probably one-third of all types of functional bleeding, is not satisfactorily explained by an excessive estrogenie supply. Kurzrok (3) points out that neither the blood nor the urine of such patients shows higher estrogenic titers. And furthermore, other tissues supplied by estrogens do not show the effects of overstimulation such as enlargement of the breasts or uterus. Kurzrok therefore feels that it is an endometrial affair, the endometrium taking more than its share of the estrogens and this in turn causing more estrogen to be produced by the ovary. And so the endometrium may be the cause of the cystic follicles so frequently found in the ovaries of such patients rather than the cystic follicles causing the hyperplastic endometrium.

IT MAY be of interest to the reader of the Journal to discuss the management of a patient with primary amenorrhea over a period of seventeen years, during which time major developments in endocrinology have occurred. Miss S. B. (Fig. 1) was first seen in the metabolism clinic at the University of Chicago in April 1936, at the age of 18 years, complaining of failure to menstruate and a lack of normal breast development. She had been under medical care elsewhere for the preceding two years without beneficial results. The therapy consisted of dessicated thyroid and several endocrinal preparations of dubious potency. Her mother stated that her birth and early childhood were entirely uneventful. Scant pubic hair was noted at 11 years of age and a few axillary hairs a year later. However, growth of hair in these regions did not progress normally. Physical examination revealed a rather stocky young woman, 167 cm. tall, weighing 138 pounds and mentally alert. Her general appearance was that of a prepubertal child...

IT IS the purpose of this paper to compare the progestational activity of a new substance, 17-alpha-hydroxyprogesterone-17-caproate, with the activity of chemically pure progesterone. 17-Alpha-hydroxyprogesterone-caproate is of interest because of the following factors: 1. 17-Alpha-hydroxyprogesterone, without esterification, has no progestational activity (1, 2). 2. The 17-ester (caproate or acetate), however, shows marked progestational activity in animal experiments (1). 3. The 17-ester (caproate or acetate), however, shows marked progestational activity in animal experiments (1). 4. Esterification of sex hormones generally causes a prolongation and, to some extent, an increase of their effects. The character of these effects (inert to highly active), however, is not changed by esterification (3, 4). 17-Alpha-hydroxyprogesterone seems to be an exception to this general rule. 5. 17-Alpha-hydroxyprogesterone is not metabolized to pregnanediol in the human (5). 6. The metabolism of 17-alpha-hydroxyprogest...

Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

THE PRESENT PAPER is a report of a 2-year survey of the estrogenic effectiveness, clincal usefulness and safety of stilbestrol (4-4′ hydroxy-a-bdiethyl stilbene). A number of other synthetic estrogenic drugs including stilbestrol dipropionate, hexestrol, and a methylated form of stilbestrol have been studied less extensively and will be reported on at a later date. In a previous clinical study (1) on ico patients who received stilbestrol for varying periods of time guarded conclusions were drawn. The present report covers a much larger group of patients given stilbestrol over an extended period. Most of the original observations can now be confirmed in the light of a great deal more collected data. The series under consideration is the largest yet reported, numbering over 600 patients, all of whom have been under observation for at least 6 months, most of them for 12 months, and some for as long as 21 months. Careful clinical and laboratory check-up has been employed throughout the investigation.

THE maintenance and activity of cells of an organ is dependent among other things on the functional adequacy of the blood supply. The functional adequacy of the circulation of any organ depends in turn on a number of factors: the blood volume, rate of blood flow, the concentration of gases, nutrients and metabolites in the blood and tissue fluid, the tissue permeability of these substances, and the area of the capillary bed. In an endocrine organ, like the adrenal cortex, these factors are especially important, as the functional activity is expressed by the pattern of blood circulation. The complexities in the morphology of the adrenal cortex of mammals are so great that it seems practical at the present time to approach experimentally only the estimation of the area of the capillary bed. This area may be expressed as a ratio of the surface of the capillary bed to the volume of tissue occupied by it (S. V.).

PREGNANCY is normally associated with a deposition of pigment in characteristic areas already pigmented. Thus the nipples and areolae, the linea alba, the vulva, the navel and the face slowly accumulate pigment during gestation. The pigmentary response to pregnancy varies in different individuals. Brunettes show a greater response than do blondes. A Japanese, Nishizaki, suggested that the degree of pigmentation is an excellent index of the general physical response to the stimulation of pregnancy. In a few individuals, the increased pigmentation of the face involving the cheeks, the forehead, and the bridge of the nose presents a characteristic picture.which has been designated as the “mask of pregnancy,” or chloasma gravidarum. These areas of increased pigmentation gradually lose their excessive pigment and slowly fade out after the patient's delivery. In recent years the pigmentary response of pregnancy has been regarded as endocrinal in origin. The first experimental evidence for melanin formation in t...

To discover whether exposure of the eye to light played any role in the pathogenesis of retrolental fibroplasia, the eyes of five premature infants were shielded for from 35 to 60 days after birth. Four of these five infants developed retrolental fibroplasia. One of the five infants developed no ocular abnormality of any kind. It is concluded that light is not an etiologic factor of retrolental fibroplasia in the premature infant.

THE interrelationship between enzymes and hormones has been a subject of much speculation. Very little information is available regarding the mechanism by which these two classes of important biological substances interact. That these organic components do influence the activity of each other has been demonstrated amply by a number of investigations conducted, for the most part, in experimental animals. Birkhauser and Zeller (1) demonstrated a sex difference in the nonspecific cholinesterase activity of the liver in rats. They found the values for these nonspecific esterases were from five to eight times greater in mature female animals than in males. Beveridge and Lucas (2) found a similar but less distinct sex difference. In their studies, the values for the enzyme level of the serum in female rats were three to five times greater than those encountered in males. More recently Sawyer and Everett (3) in a much more extensive study found that in rats, following ovariectomy, there was a rapid decline of no...

The existence of a malformation in a fetus is not often associated with abnormalities of pregnancy or labor. The chief concern of the obstetrician is in counseling the parents concerning future childbearing. Malformations were reported by the National Office of Vital Statistics as responsible for 4.4 neonatal deaths per 1000 live births during the first 3 months of 1950. They accounted for 24% of the deaths of infants weighing over 2500 gm; 7% of the deaths of infants weighing under 2500 gm; that were born in the U.S. during this interval. In a study of 5000 consecutive births at the Chicago Lying-in Hospital in 1951 and 1952, 210 surviving infants were found to have certain conditions considered to be malformations. It was thought that not more than 10% of these infants, or 4.2 per 1000 births, would be handicapped by the malformations. Coupling this with the deaths and stillbirths occurring during the same period gives a total of 10.6 per 1000 births. Thus about 1% of reported births are infants with lethal or handicapping malformations which can be diagnosed at or soon after birth. Lethal malformations involved the central nervous system more often than any other part of the body, with anencephaly the most common single anomaly. Cardiac malformations were second, with those of the gastrointestinal and genitourinary tracts about equal in third and fourth places. Malformations occur more commonly in males than females and in white than non-white and in the children of women who are near the beginning or end of the age when reproduction is possible. Genetic disturbances can rarely be shown to be the cause of lethal malformations.

THE discovery of gonadotropic principles in pregnancy urine and in extracts of the anterior lobe of the pituitary gland heralded great expectations in the therapy of ovarian failure. The responses of laboratory animals to these gonadotropins justified some of our early expectations. However, further observations in the laboratory and in the clinic have led to a maze of ideas and conclusions. This is particularly true in the therapeutic application of the gonadotropins that are available for gynecologic practice. The lack of uniformity in the results obtained from the clinical use of gonadotropins is due to several factors. In the first place, the physiology of human reproduction is not well understood. Although the general principles underlying the endocrine control of the sex cycle are known, there are many defects in our knowledge which must be removed before successful therapy can be developed. In the second place, the clinical problem of ovarian failure is still a crude entity, the etiology of which m...

A system for the continuous visual monitoring of the fetal electrocardiogram is described. Six labor rooms were instrumented and connected to the central monitor recording room by cables. The signals may be observed on six oscilloscopes mounted in a central console. Provision is made for recording on a standard paper recorder. A remote six oscilloscope unit is located in the physicians' staff room that simultaneously displays the signals. Early experience with the monitor is described briefly. We have demonstrated that the instrumentation described provides an ideal approach to the continuous monitoring of the fetal heart throughout labor and delivery and for the study of the fetal-maternal circulation.

THE estrogens are the most widely used and abused of endocrinal substances. When they are used physiologically and intelligently they are valuable preparations. However, there are those who feel that their widespread misuse may more than outweigh their value. In these random comments we shall discuss a few observations on the use of estrogens. The ingenuity of our chemists and pharmaceutical companies has provided us with a host of preparations. In the first place there are the natural estrogens and their derivatives. The basic substances estradiol, estriol and estrone have been extracted from a variety of sources. Estradiol is the most potent naturally-occurring estrogen; estriol and estrone are much less potent, for these are the products of metabolism of estradiol. The naturallyoccurring estrogens are available in pure form, in impure mixtures such as the conjugated estrogens, and as synthetic derivatives such as ethinyl estradiol. Lastly, there are the stilbene-hexane compounds, chemically unrelated t...

Lillie in 1917 described the freemartin and attributed this masculinization of the female twin to the presence of androgenic hormones reachingit from the male twin through the anastomosing circulation in the placenta. Since then numerous investigations have been carried out in an attempt to determine whether or not his conclusions concerning the etiology of the condition were correct. These experiments for the most part were designed to answer the following questions: (1) Do fetal gonads normally produce specific sex hormones? (2) Can the gonads be stimulated to produce such hormones even though they do not do so under normal circumstances? (3) Is it possible for hormones normally present or those resulting from abnormal stimulation of the fetal gonads to affect the development of the reproductive system? (4) Is it possible to alter the development of the reproductive tract by the artificial introduction of hormones into the environment in which development of the fetal gonads is taking place? The last qu...