Allan Palmer

Estrogenic Hormone in the Urine and Tumor of a Patient with a Granulosa Cell Tumor of the Ovary

Summary Estrogenic hormone determinations on the tumor and urine of a patient with a granulosa cell tumor of the ovary are reported. Values for the hormone are calculated as estrone. The content of the tumor was found to be 11,700.0 gamma (11.7 mg.) per kilogram desiccated tumor tissue associated with a maximum urinary excretion of 86.6 gamma per twenty-four hours while the patient was bleeding. Beginning the first day after operation the urinary excretion of estrogenic hormone fell to normal. Comparable values from other cases recorded in the literature are tabulated.

Hormones in Urine of a Normal Non-Pregnant Woman.

Summary This report concerns the daily excretion of estrogenic hormone in both free and combined chemical forms during one menstrual cycle of a normal muciparous woman. The possible excretion of gonadotropic hormone is reported merely that comparisons may be made with the reports of other workers. I feel that the excretion of this has not been demonstrated. Evidence of a significant association between the events of the menstrual cycle and changes in the amount and chemical form of estrin is discussed.

The basal body temperature of women

I N ORDER to get the most out of a woman’s basal body temperature as a diagnostic procedure in the investigation of infertility and other gynecological endocrine disorders it is imperative that the temperature be taken at the same time early every morning under strictly basal conditions. Advocates of the use of the “waking temperature ” (B ar on and Wiesner, 1945, and others) without t regard for the time factor cannot expect to obtain temperature curves which accurately reflect the effect of the ovarian hormones. Even though regarded as being under basal conditions a woman who awakens late in the morning does not have as low a body temperature at 10 to 11 A.M. as she has at 6 to 7 A.M. Because of diurnal variation the difference between her 6 A.M. and her 11 A.M. temperatures on the same day, even while sleeping continuously, may be as great as or greater than the difference between her “basal” preovulatory and postovulatory temperatures.

Clinical Experiments with Diethylstilbestrol

Abstract 1. 1. Zuckermans experimental data on the production of artificial menstrual cycles and a fluctuating uterine threshold to estrone in the monkey are reviewed. 2. 2. Artificial menstrual cycles (diethylstilbestrol withdrawal bleeding) were induced by cyclical diethylstilbestrol therapy in 4 patients with primary amenorrhea and in 4 postmenopausal women. 3. 3. Forty-two milligrams were found to be an optimum oral dose of diethylstilbestrol which in fourteen days would produce a normal degree of endometrial proliferation and would be followed by uterine bleeding. 4. 4. Seventy milligrams of diethylstilbestrol by mouth in fourteen days produced a slight degree of cystic glandular hyperplasia of the endometrium. 5. 5. The consistency of the latent interval that precedes withdrawal bleeding in the group of primary and postmenopausal amenorrheic patients, regardless of variation in dosage and manner of administration, leads one to believe that a fluctuating uterine threshold to estrogen may not be a factor with which to be concerned as it will be shown to be in patients with uterine bleeding (Palmer2), and as it is known to be in the ovariectomized monkey.

Excretion of hormones in a case of habitual abortion

Abstract The quantitative hormone determinations and discussion pertaining to them in a case of habitual abortion are presented. The relationship of estrogenic hormone excretion to parturition is demonstrated.

Method of Preparing Mice for Quantitative Determination of Urinary Estrogen.

The methods of biological assay for urinary estrogen in use at the present time are dependent upon the production of estrus in a castrated mouse or rat. Various modifications of the original Allen-Doisy test have been used, such variations being single or multiple injections of either aqueous, glycerol, or oily extracts into castrated or immature normal mice or rats. Methods utilizing male animals and fish have not as yet proved of any great value for quantitative purposes. Chemical methods for the determination of urinary estrogen have been proposed by Kober, 1 Cohen and Marrian, 2 David, 3 Cartland et al., 4 Schmulovitz and Wylie, 5 , 6 and Pincus et al. 7 Chemical tests based on color changes in the test tube and comparison with standards are preferable to biological tests. The disadvantage of chemical tests is chiefly their inapplicability to the estimation of estrogens in the urine of non-pregnant women. For this purpose we must, for the present, still resort to biological means. A biological test for urinary estrogen must be for the biological activity of all the estrogenic substances present in the urinary extract. The test cannot be specific for, or differentiate between, different forms of the hormone. The advantage of the biological method is its ability to demonstrate very small amounts of estrogenic hormone in the presence of inactive impurities. The disadvantages are the troublesome time consuming procedures and the necessity of maintaining a supply of test animals. The greatest disadvantage is the source of error and variation in methods. More than a 4000% variation can he demonstrated in the procedures 3 now used. This paper is presented in an ctiort to decrease the large percent of error and variation. Our test animal I)!- choicc has ken the castrated adult female mouse. just as chemically piire hornic me ior assay is tested against a knon-n ctantlartl hormone.

A Source of Error in Gonadotropic Hormone Determihations.

This report is presented in an effort to show that determinations for gonadotropic hormone content of the urine are frequently erroneous due to the precipitation of contaminating amounts of fat-insoluble or combined estrogen. Concerning urinary gonadotropins there is no doubt that pregnant women excrete a substance capable of producing corpora lutea in the ovaries of normal infantile animals. Some women in the menopause excrete a gonadotropic hormone capable of provoking follicle growth in the ovaries of hypophysectomized rats or mice. A gonadotropic hormone prepared from the pituitary and capable of interstitial cell stimulation has been described, but its detection if present in the urine, depends also upon the use of hypophysectomized animals. For studying the urine of non-pregnant women most workers have resorted to the use of intact animals and depend upon more cursory and unreliable criteria for the estimation of gonadotropic hormone. Speaking collectively, their criteria have been the appearance, in infantile rats or mice as old as 32 days and within periods up to as long as 130 hours after injection, of follicle growth, interstitial cell hypertrophy, increase in uterine and ovarian size and weight, establishment of vaginal introitus, and estrus. The reactions in the lower tubular tract have been interpreted as gonadotropic responses in some instances, in the absence of demonstrable changes in the gonads. The uterus and its endometrium depend upon the ovaries for changes in histologic structure. If the uterus of an infantile rodent were stimulated directly without the medium of the ovaries but in their presence, by an estrogenic substance that does not in any way depress ovarian activity, then an independent activation of the ovaries by the animals own pituitary might occur. Hypothetically this pituitary activity can be construed as being either independent and spontaneous, or as a result of stimulation by an estrogen.

Transmission of Estrogenic Substances from Animal to Animal

We have been treating female white mice with massive doses of estrone (200 I.U.) painted on the skin.∗ To our astonishment a group of 25 untreated spayed mice, whose vaginal smears were all negative, all went into estrus. It had been our custom in treating or examining animals to take them from their cage, treat, and then place in a temporary box until all animals in a cage were removed, then return them to their cage. No transmission of estrogenic substances has been noted among a large number of female mice treated with subcutaneous injections of 1–10 I.U. of estrone. To trace out the source of estrogenic stimulation we placed a standard mouse in the cage of each group receiving estrone, and one in the temporary box during a morning when the mice were being treated with estrone. A standard mouse is a young spayed adult known to respond to 2 I.U. of estrone administered subcutaneously. All of these standard mice went into estrus and remained in estrus for about 2 weeks. There could be only 2 probable routes of transmission and of reception of the estrogenic substance, i. e., from the skin, and from the excreta, and through the skin, and through the mouth. To make a crude estimate of these factors we placed a standard mouse with a muzzle on in the cage with estrone-treated animals. A mouse in, a paraffin sack, with only its head exposed, was also placed in a cage with estrone-treated animals. Two other muzzled and sacked animals were placed in the bottoms of cages of estrone-treated animals. The cages have false bottoms. Except for the period of exposure each standard mouse was caged separately.