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ARTICLE |

THE ESTROGENIC SUBSTANCES FREE

EDWARD A. DOISY, Ph.D., D.Sc.
JAMA. 1941;116(6):501-505. doi:10.1001/jama.1941.62820060004011
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Although several investigators1 contributed to the early development of research on estrogens, rapid progress did not begin until after the publication of the vaginal smear reaction2 for the detection of these substances. The work was given additional impetus by the discovery of the high concentration of estrogens in the urine of pregnant women and in the urine of pregnant mares.3 These discoveries, which provided excellent sources of the estrogens and the means of quantitative determination, were of paramount importance to the isolation of the estrogens and the determination of their structure, as well as to the introduction of an ample supply of estrogenic substances for therapeutic use. The subsequent availability of pure estrogens has permitted an investigation of their role in sex physiology, particularly with respect to the estrous and the menstrual cycle, and of their interrelationships with other internal secretions.

CHEMISTRY OF ESTROGENIC SUBSTANCES  At this

REFERENCES

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Israel, S. L.; Meranze, D. R., and Johnston, C. G.:  The Inactivation of Estrogen by the Liver. Observations on the Fate of Estrogen in Heart-Lung and Heart-Lung-Liver Perfusion Systems , Am. J. M. Sc. 194:835 ( (Dec.) ) 1937;.
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Westerfeld, W. W.:  The Inactivation of Oestrone , Biochem. J. 34:51 ( (Jan.) ) 1940;.
Marker, R. E.; Rohrmann, Ewald; Lawson, E. J., and Wittle, E. L.:  The Isolation of Oestranediols from Human Non-Pregnancy Urine , J. Am. Chem. Soc. 60:1901 ( (Aug.) ) 1938;.
Pincus, Gregory, and Zahl, P. A.:  The Biogenesis of Primary Sex Hormones: The Fate of Estrins Injected into the Rabbit , J. Gen. Physiol. 20:879 ( (July) ) 1937;.
Smith, G. V., and Smith, O. W.:  Observations Concerning the Metabolism of Estrogens in Women , Am. J. Obst. & Gynec. 36:769 ( (Nov.) ) 1938;.
Smith, G. V.; Smith, O. W., and Pincus, Gregory:  Total Urinary Estrogen, Estrone and Estriol During a Menstrual Cycle and a Pregnancy , Am. J. Physiol. 121:98 ( (Jan.) ) 1938;.
Pincus, Gregory, and Graubard, Mark:  Estrogen Metabolism in Cancerous and Non-Cancerous Women , Endocrinology 26:427 ( (March) ) 1940;.
Deansley, R., and Parkes, A. S.:  Factors Influencing the Effectiveness of Administered Hormones , Proc. Roy. Soc., London, s. B. 124:279 ( (Dec. 7) ) 1937;.
Salmon, U. J.; Geist, S. H., and Walter, R. I.:  Inhibitory Effect of Implanted Estrogenic Hormone Crystals upon Post-Menopause and Castration Hypophysis of Women , Proc. Soc. Exper. Biol. & Med. 43:424 ( (Feb.) ) 1940;.
Bennett, H. G.; Biskind, Gerson, and Mark, Jerome:  Subcutaneous Implantation of Compressed Crystalline Theelin Pellets in the Treatment of Menopausal Cases , Am. J. Obst. & Gynec. 39:504 ( (March) ) 1940;.
Lyons, W. R., and Templeton, H. J.:  Intravaginal Assay of Urinary Estrin , Proc. Soc. Exper. Biol. & Med. 33:587 ( (Jan.) ) 1936;.
Selye, Hans:  On the Toxicity of Oestrogens with Special Reference to Stilbestrol , Canad. M. A. J. 41:48 ( (July) ) 1939;.
Shorr, Ephraim; Robinson, F. H., and Papanicolaou, G. N.:  A Clinical Study of the Synthetic Estrogen Stilbestrol , J. A. M. A. 113:2312 ( (Dec. 23) ) 1939;.
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Kurzrok, Raphael; Wilson, Leo, and Perloff, W. H.:  The Action of Diethylstilbestrol in Gynecological Dysfunctions , Endocrinology 26:581 ( (April) ) 1940;.

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Adler, L.:  Zur Physiologie und Pathologie der Ovarialfunktion , Arch. f. Gynäk. 95:349, 1912;.
Fellner, O. O.:  Experimentell erzeugte Wachstumsveränderungen am weiblichen Genitale der Kaninchen , Zentralbl. f. allg. Path. u. path. Anat. 23:673, 1912;.
Herrmann, E.:  Ueber eine wirksame Substanz im Eierstocke und in der Placenta , Monatschr. f. Geburtsh. u. Gynäk. 41:1, 1915;.
Frank, R. T., and Rosenbloom, J.:  Physiologically Active Substances Contained in the Placenta and in the Corpus Luteum , Surg., Gynec. & Obst. 21:646, 1915;.
Allen, Edgar, and Doisy, E. A.:  An Ovarian Hormone: Preliminary Report on Its Localization, Extraction and Partial Purification and Action in Test Animals , J. A. M. A. 81:819 ( (Sept. 8) ) 1923;.
Aschheim, Selmar, and Zondek, Bernhard:  Hypophysenvorderlappen Hormon und Ovarialhormon im Harm von Schwangeren , Klin. Wchnschr. 6:1322 ( (July 9) ) 1927;.
Zondek, Bernhard:  Mass Excretion of Oestrogenic Hormone in the Urine of the Stallion , Nature, London 133:209 ( (Feb. 10) ) 1934;.
Adam, N. K.; Danielli, J. F.; Dodds, E. C.; King, H.; Marrian, G. F.; Parkes, A. S., and Rosenheim, O.:  Nomenclature of the Oestrin Group , Nature, London 132:205 ( (Aug. 5) ) 1933;.
Veler, C. D.; Thayer, S. A., and Doisy, E. A.:  The Preparation of the Crystalline Follicular Ovarian Hormone: Theelin , J. Biol. Chem. 87:357 ( (June) ) 1930;.
 The Nomenclature of Estrus-Producing Compounds, Report of the Council on Pharmacy and Chemistry , J. A. M. A. 107:1221 ( (Oct. 10) ) 1936;.
Doisy, E. A.; Veler, C. D., and Thayer, S. A.:  Folliculin from the Urine of Pregnant Women , Am. J. Physiol. 90:329 ( (Oct.) ) 1929;.
Butenandt, Adolf:  Ueber "Progynon" ein krystallisiertes weibliches Sexualhormon , Naturwissenschaften 17:878, 1929;.
de Jongh, S. E.; Kober, S., and Laqueur, Ernst:  Ueber Identität des Brunsthormons (Menformon) aus Harn schwangerer Frauen und aus Harn trächtiger Pferde , Biochem. Ztschr. 240:247, 1931;.
Häussler, E. P.:  Ueber das Vorkommen von α-Follikelhormon (3-oxy-17 keto-1,3,5-oestratriën) im Hengsturin , Helvet. chim. acta 17:531, 1934;.
Deulofeu, Venancio and Ferrari, J.:  Krystallisiertes α-Follikelhormon aus Hengstharn , Ztschr. f. physiol. Chem. 226:192, 1934;.
Dingemanse, E.; Laqueur, Ernst, and Mühlbock, O.:  Chemical Identification of Oestrone in Human Male Urine , Nature, London ( (supp.) ) 141:927 (May 21) 1938;.
Westerfeld, W. W.; MacCorquodale, D. W.; Thayer, S. A., and Doisy, E. A.:  The Isolation of Theelin from Human Placenta , J. Biol. Chem. 126:195 ( (Nov.) ) 1938;.
Beall, D.:  Isolation of Estrone from the Adrenal Gland , Nature, London 144:76 ( (July 8) ) 1939;.
Butenandt, Adolf, and Jacobi, H.: Ueber die Darstellung eines krystallisierten pflanzlichen Tokokinins (Thelykinins) und seine Identifizierung mit dem α-Follikelhormon , Ztschr. f. physiol. Chem. 218:104, 1933;.
Westerfeld, W. W.; Thayer, S. A.; MacCorquodale, D. W., and Doisy, E. A.:  The Ketonic Estrogen of Sow Ovaries , J. Biol. Chem. 126:181 ( (Nov.) ) 1938;.
Schachter, Benjamin, and Marrian, G. F.:  The Isolation of Estrone Sulfate from the Urine of Pregnant Mares , J. Biol. Chem. (Nov.) 126:663, 1938;.
Marrian, G. F.:  Observations on the Chemical Nature of Crystalline Oestrin , J. Soc. Chem. & Ind. 49:515, 1930;.
Doisy, E. A.; Thayer, S. A.; Levin, Louis, and Curtis, J. M.:  A New Tri-Atomic Alcohol from the Urine of Pregnant Women , Proc. Soc. Exper. Biol. & Med. 28:88 ( (Oct.) ) 1930;.
Browne, J. S. L.:  The Chemical and Physiological Properties of Crystalline Estrogenic Hormones , Canad. J. Research 8:180 ( (Feb.) ) 1933;.
Skarżyński, B.:  An Oestrogenic Substance from Plant Material , Nature, London 131:766 ( (May 27) ) 1933;.
Cohen, S. L., and Marrian, G. F.:  The Isolation and Identification of a Combined Form of Œstriol in Human Pregnancy Urine , Biochem. J. 30:57 ( (Jan.) ) 1936;.
Butenandt, Adolf, and Hildebrandt, F. M.:  Ueber ein zweites Hormonkrystallisat aus Schwangerenharn und seine physiologischen und chemischen Beziehungen zum krystallisierten Follikelhormon , Ztschr. f. physiol. Chem. 199:243, 1931;.
MacCorquodale, D. W.; Thayer, S. A., and Doisy, E. A.:  The Isolation of the Principal Estrogenic Substance of Liquor Folliculi , J. Biol. Chem. 115:435 ( (Sept.) ) 1936;.
Wintersteiner, Oskar; Schwenk, Erwin, and Whitman, Bradley:  Estrogenic Dihydroxy Compounds in Urine of Pregnant Mares , Proc. Soc. Exper. Biol. & Med. 32:1087 ( (April) ) 1935;.
Huffman, M. N.; MacCorquodale, D. W.; Thayer, S. A.; Doisy, E. A.; Smith, G. V., and Smith, O. W.:  The Isolation of α-Dihydrotheelin from Human Pregnancy Urine , J. Biol. Chem. 134:591 ( (July) ) 1940;.
Huffman, M. N.; Thayer, S. A., and Doisy, E. A.:  The Isolation of α-Dihydrotheelin from Human Placenta , J. Biol. Chem. (July) 133:567, 1940;.
Girard, André; Sandulesco, A.; Fridenson, A., and Rutgers, J. J.:  Sur une nouvelle hormone sexuelle cristallisée retirée de l'urine des juments gravides , Compt. rend. Acad. d. sc. 194:909 ( (March 7) ) 1932;
 Sur une nouvelle hormone sexuelle cristallisée , GirardCompt. rend. Acad. d. sc. 195:981 ( (Nov. 21) ) 1932;.
Hirschmann, H., and Wintersteiner, Oskar:  The Isolation of Estrogenic Diols from the Urine of Pregnant Mares , J. Biol. Chem. 122:303 ( (Jan.) ) 1938;.
Bachmann, W. E.; Cole, Wayne, and Wilds, A. L.:  The Total Synthesis of the Sex Hormone Equilenin , J. Am. Chem. Soc. 61:974 ( (April) ) 1939;
62: 824 (April) 1940.
Marker, R. E.:  Reduction of Naphtholic Steroids to Phenolic Steroids: Equilenin , J. Am. Chem. Soc. 60: 1897 ( (Aug.) ) 1938;.
Cook, J. W.; Dodds, E. C., and Hewett, C. L.:  A Synthetic Oestrus-Exciting Compound , Nature, London 131:56 ( (Jan. 14) ) 1933;.
Campbell, N. R.; Dodds, E. C.; Lawson, W., and Noble, R. L.:  Biological Effects of the Synthetic Oestrogen Hexoestrol 4: 4′-Dihydroxy-γ: ξ-Diphenyl-n-Hexane , Lancet 2:312 ( (Aug. 5) ) 1939;.
Dodds, E. C.; Goldberg, L.; Lawson, W., and Robinson, R.:  Synthetic Oestrogenic Compounds Related to Stilbene and Diphenylethane , Proc. Roy. Soc., London, s. B , 127:140 ( (May 18) ) 1939;
 Oestrogenic Activity of Certain Synthetic Compounds , Nature, London 141:247 ( (Feb. 5) ) 1938;.
Dodds, E. C.; Lawson, W., and Noble, R. L.:  Biological Effects of the Synthetic Oestrogenic Substance 4: 4′-dihydroxy-α: β-Diethylstilbene , Lancet 1:1389 ( (June 18) ) 1938;.
Robson, J. M., and Schönberg, A.:  Oestrous Reactions, Including Mating, Produced by Triphenyl Ethylene , Nature, London 140:196 ( (July 31) ) 1937;.
Girard, André, and Sandulesco, G.:  Sur une nouvelle série de réactifs du groupe carbonyle, leur utilisation à l'extraction des substances cetoniques et la caracterisation microchimique des aldéhydes et cetones , Helvet. chim. acta 19:1095, 1936;.
Wintersteiner, Oskar:  Estrogenic Diols from the Urine of Pregnant Mares , in Cold Spring Harbor Symposia on Quantitative Biology , Cold Spring Harbor, L. I., New York, The Biological Laboratory, 1937;, vol. 5, p. 25.
Miescher, K., and Scholz, C.:  Ueber Ester der Follikelhormonreihe , Helvet. chim. acta 20:263, 1937;
 Ueber neue Verbindungen der Follikelhormonreihe , MiescherHelvet. chim. acta 20:1237, 1937;.
Kober, S.:  Eine kolorimetrische Bestimmung des Brunsthormons (Menformon) , Biochem. Ztschr. 239:209, 1931;.
Cohen, S. L., and Marrian, G. F.:  The Application of the Kober Test to the Quantitative Estimation of Oestrone and Oestriol in Human Pregnancy Urine , Biochem. J. 28:1603, 1934;.
Bachman, Carl:  Photometric Determination of Estrogens: A Modified Kober Reaction for Determining the Total Estrogens in a Mixture of Estrogenic Steroids , J. Biol. Chem. 131:455 ( (Dec.) ) 1939;
 A New Color Reaction for Estriol , BachmanJ. Biol. Chem. 131:463 ( (Dec.) ) 1939;.
Butenandt, Adolf; Weidlich, H. A., and Thompson, H.:  Neue Beiträge zur Konstitution des Follikel-hormons , Ber. d. deutsch. chem. Gesellsch. 66:601, 1933;.
Haworth, R. D., and Sheldrick, George:  Synthesis of Alkylphenanthrenes. 7-Hydroxyl: 2-Dimethylphenanthrene , J. Chem. Soc., London , 1934;, pt. (1) , p. 864.
Cohen, A.; Cook, J. W., and Hewett, C. L.:  The Synthesis of Compounds Related to the Sterols, Bile Acids, and Oestrus-Producing Hormones. Experimental Evidence of the Complete Structure of Oestrin, Equilin and Equilenin , J. Chem. Soc., London 1935;, pt. (1) , p. 445.
Allen, Edgar:  The Physiology of Estrogenic Principles , J. A. M. A. 104:1498 ( (April 27) ) 1935;.
Allen, Edgar; Danforth, C. H., and Doisy, E. A.: Sex and Internal Secretions , ed. 2, Baltimore, Williams & Wilkins Company, 1939;.
Allen, Edgar; Francis, B. F.; Robertson, L. L.; Colgate, C. E.; Johnston, C. G.; Doisy, E. A.; Kountz, W. B., and Gibson, H. V.:  The Hormone of the Ovarian Follicle; Its Localization and Action in Test Animals and Additional Points Bearing upon the Internal Secretions of the Ovary , Am. J. Anat. 34:133 ( (Sept.) ) 1924;.
Papanicolaou, G. N.:  The Sexual Cycle in the Human Female as Revealed by Vaginal Smears , Am. J. Anat. ( (supp.) ) 52:519 (May) 1933;.
Papanicolaou, G. N., and Shorr, Ephraim:  The Action of Ovarian Follicular Hormone in the Menopause, as Indicated by Vaginal Smears , Am. J. Obst. & Gynec. 31:806 ( (May) ) 1936;.
Werner, A. A.; Jones, Grey; Roberts, John; Broun, G. O.; Neilson, C. H., and Rothermich, N. O.:  Effective Clinical Dosages of Theelin in Oil, Based on Study of Sixteen Castrate Women , J. A. M. A. 109:1027 ( (Sept. 25) ) 1937;.
Lewis, R. M.:  A Study of the Effects of Theelin on Gonorrheal Vaginitis in Children , Am. J. Obst. & Gynec. 26:593 ( (Oct.) ) 1933;.
Lewis, R. M., and Adler, E. L.:  Gonorrheal Vaginitis: Results of Treatment with Different Preparations and Amounts of Estrogenic Substance , J. A. M. A. 106:2054 ( (June 13) ) 1936;.
Allen, Edgar; Smith, G. M., and Gardner, W. U.:  Accentuation of the Growth Effect of Theelin on Genital Tissues by Arrest of Mitosis with Colchicine , Anat. Rec. 67 ( (supp.) ):49 (Dec.) 1936;
 Accentuation of the Growth Effect of Theelin on Genital Tissues of the Ovariectomized Mouse by Arrest of Mitosis with Colchicine , Am. J. Anat. 61:321 ( (July) ) 1937;.
Markee, J. E.:  Menstruation in Intra-Ocular Endometrial Transplants in Macaca Mulatta , Anat. Rec. 64 ( (supp. 3) ):32 (March) 1936;.
Allen, Edgar; Francis, B. F.; Robertson, L. L.; Colgate, C. E.; Johnston, C. G.; Doisy, E. A.; Kountz, W. B., and Gibson, H. V.:  The Hormone of the Ovarian Follicle; Its Localization and Action in Test Animals and Additional Points Bearing upon the Internal Secretions of the Ovary , Am. J. Anat. 34:133 ( (Sept.) ) 1924;.
Allen, Edgar:  The Menstrual Cycle of the Monkey, Macacus Rhesus , Contrib. Embryol. 19:1, 1927;.
Bülbring, Edith, and Burn, J. H.:  The Estimation of Oestrin and of Male Hormone in Oily Solution , J. Physiol. 85:320 ( (Nov. 22) ) 1935;.
Dorfman, R. I.; Gallagher, T. F., and Koch, F. C.:  Nature of Estrogenic Substance in Human Male Urine and Bull Testis , Endocrinology 19:33 ( (Jan.) -Feb.) 1935;.
Talbot, N. B.; Lowry, O. H., and Astwood, E. B.:  Influence of Estrogen on the Electrolyte Pattern of the Immature Rat Uterus , J. Biol. Chem. 132:1 ( (Jan.) ) 1940;.
Reynolds, S. R. M.:  Action of Theelol (Tri-Hydroxy-Oestrin) on Uterine Fistulae in the Unanesthetized Rabbit , Proc. Soc. Exper. Biol. & Med. 30:1165 ( (May) ) 1933;
 Studies on the Uterus: VI. The Effect of Oestrin on the Uterine Fistula During Pseudo-Pregnancy , Am. J. Physiol. 98:230 ( (Sept.) ) 1931;.
Smith, M. G.:  Interruption of Pregnancy in the Rat by the Injection of Ovarian Follicular Extract , Bull. Johns Hopkins Hosp. 39:203 ( (Oct.) ) 1926;.
Levin, Louis; Katzman, P. A., and Doisy, E. A.:  Effects of Estrogenic Substances and the Luteinizing Factor on Pregnancy in the Albino Rat , Endocrinology 15:207 ( (May) -June) 1931;.
Burdick, H. O., and Pincus, Gregory:  The Effect of Oestrin Injections upon the Developing Ova of Mice and Rabbits , Am. J. Physiol. 111:201 ( (Feb.) ) 1935;.
Whitney, Rae, and Burdick, H. O.:  Tube-Locking of Ova by Oestrogenic Substances , Endocrinology 20:643 ( (Sept.) ) 1936;.
Sand, K.:  Transplantation der Keimdrüsen bei Wirbeltieren , in Bethe, Albrecht; von Bergmann, G.; Embden, Gustav, and Ellinger, Alexander: Handbuch der normalen und pathologischen Physiologie , Berlin, Julius Springer, 1926;, vol. 74.
Allen, Edgar, and Doisy, E. A.:  The Induction of a Sexually Mature Condition in Immature Females by Injection of the Ovarian Follicular Hormone , Am. J. Physiol. 69:577, 1924;
C. W. Turner in "Sex and Internal Secretions"
Loeb, Leo:  Internal Secretions as a Factor in the Origin of Tumors , J. M. Research 40:477 ( (Sept.) ) 1919;.
Cori, C. F.:  The Influence of Ovariectomy on the Spontaneous Occurrence of Mammary Carcinomas in Mice , J. Exper. Med. 45:983 ( (June) ) 1927;.
Lacassagne, Antoine:  Apparition de cancers de la mamelle chez la souris mâle, soumise à des injections de folliculine , Compt. rend. Acad. d. sc. 195:630 ( (Oct. 10) ) 1932;.
Leo Loeb appeared in the first edition of Glandular Physiology and Therapy: A Symposium, Chicago, American Medical Association, 1935 .
Addison, W. H. F.:  The Cell-Changes in the Hypophysis of the Albino Rat, After Castration , J. Comp. Neurol. 28:441, 1917;.
Hohlweg, Walter, and Dohrn, Max:  Beziehung zwischen Hypophysenvorderlappen und Keimdrüsen , Wien. Arch. f. inn. Med. 21:337 ( (July 15) ) 1931;.
Nelson, W. O.:  Effect of Oestrin and Gonadotropic Hormone Injections upon Hypophysis of the Adult Rat , Proc. Soc. Exper. Biol. & Med. 32:452 ( (Dec.) ) 1934;.
Halpern, S. R., and D'Armour, F. E.:  Effects of Estrin upon Gonads, Mammary Glands and Hypophysis of the Rat , Proc. Soc. Exper. Biol. & Med. 32:108 ( (Oct.) ) 1934;.
Engle, E. T.:  Effect of Daily Transplants of the Anterior Lobe from Gonadectomized Rats on Immatrue Test Animals , Am. J. Physiol. 88:101 ( (Feb.) ) 1929;.
Hohlweg, W.:  Veränderungen des Hypophysenvorderlappens und des Ovariums nach Behandlung mit grossen Dosen von Follikelhormon , Klin. Wchnschr. 13:92 ( (Jan. 20) ) 1934;.
Selye, Hans; Collip, J. B., and Thomson, D. L.:  Effect of Oestrin on Ovaries and Adrenals , Proc. Soc. Exper. Biol. & Med. 32:1377 ( (May) ) 1935;.
Fevold, H. L.; Hisaw, F. L., and Greep, R.:  Effect of Oestrin on the Activity of the Anterior Lobe of the Pituitary , Am. J. Physiol. 114:508 ( (Jan.) ) 1936;.
Hohlweg, Walter, and Chamorro, Antonio:  Ueber die luteinisierende Wirkung des Follikelhormons durch Beeinflussung der luteogenen Hypophysenvorderlappensekretion , Klin. Wchschr. 16:196 ( (Feb. 6) ) 1937;.
Katzman, P. A.:  A Note on the Effect of Theelin, Theelol and the Luteinizing Substance on Reproduction , Proc. Soc. Exper. Biol. & Med. 29:700 ( (March) ) 1932;.
Allen, Edgar, and Diddle, A. W.:  Ovarian Follicular Hormone Effects on the Ovaries , Am. J. Obst. & Gynec. 29:83 ( (Jan.) ) 1935;.
Nelson, W. O.:  Endocrine Control of Mammary Gland , Physiol. Rev. 16:488 ( (July) ) 1936;.
Folley, S. J.:  The Effect of Estrogenic Hormones on Lactation and on the Phosphatase of the Blood and Milk of the Lactating Cow , Biochem. J. 30:2262 ( (Dec.) ) 1936;.
Gardner, W. U., and Pfeiffer, C. A.:  Skeletal Changes in Mice Receiving Estrogens , Proc. Soc. Exper. Biol. & Med. 37:678 ( (Jan.) ) 1938;.
Juhn, Mary, and Gustavson, R. G.:  A Forty-Eight Hour Test for the Female Hormone with Capon Feathers as Indicator , Proc. Soc. Exper. Biol. & Med. 27:747 ( (May) ) 1930;.
Pfeiffer, C. A., and Gardner, W. U.:  Skeletal Changes and Blood Serum Calcium Level in Pigeons Receiving Estrogens , Endocrinology 23:485 ( (Oct.) ) 1938;.
Lorenz, F. W.; Chaikoff, I. L., and Entenman, C.:  Endocrine Control of Lipid Metabolism in Bird: The Effects of Estrin on the Blood Lipids of the Immature Domestic Fowl , J. Biol. Chem. 126:763 ( (Dec.) ) 1938;.
 Report of the Second Conference on the Standardization of Sex Hormones . League of Nations Quart. Bull. Health Organ. 4:618, 1935;.
Zondek, Bernhard:  Ueber das Schicksal des Follikelhormons (Follikulin) im Organismus , Skandinav. Arch. f. Physiol. 70:133, 1934;.
Israel, S. L.; Meranze, D. R., and Johnston, C. G.:  The Inactivation of Estrogen by the Liver. Observations on the Fate of Estrogen in Heart-Lung and Heart-Lung-Liver Perfusion Systems , Am. J. M. Sc. 194:835 ( (Dec.) ) 1937;.
Heller, C. G.:  Metabolism of the Estrogens , Endocrinology 26:619 ( (April) ) 1940;.
Westerfeld, W. W.:  The Inactivation of Oestrone , Biochem. J. 34:51 ( (Jan.) ) 1940;.
Marker, R. E.; Rohrmann, Ewald; Lawson, E. J., and Wittle, E. L.:  The Isolation of Oestranediols from Human Non-Pregnancy Urine , J. Am. Chem. Soc. 60:1901 ( (Aug.) ) 1938;.
Pincus, Gregory, and Zahl, P. A.:  The Biogenesis of Primary Sex Hormones: The Fate of Estrins Injected into the Rabbit , J. Gen. Physiol. 20:879 ( (July) ) 1937;.
Smith, G. V., and Smith, O. W.:  Observations Concerning the Metabolism of Estrogens in Women , Am. J. Obst. & Gynec. 36:769 ( (Nov.) ) 1938;.
Smith, G. V.; Smith, O. W., and Pincus, Gregory:  Total Urinary Estrogen, Estrone and Estriol During a Menstrual Cycle and a Pregnancy , Am. J. Physiol. 121:98 ( (Jan.) ) 1938;.
Pincus, Gregory, and Graubard, Mark:  Estrogen Metabolism in Cancerous and Non-Cancerous Women , Endocrinology 26:427 ( (March) ) 1940;.
Deansley, R., and Parkes, A. S.:  Factors Influencing the Effectiveness of Administered Hormones , Proc. Roy. Soc., London, s. B. 124:279 ( (Dec. 7) ) 1937;.
Salmon, U. J.; Geist, S. H., and Walter, R. I.:  Inhibitory Effect of Implanted Estrogenic Hormone Crystals upon Post-Menopause and Castration Hypophysis of Women , Proc. Soc. Exper. Biol. & Med. 43:424 ( (Feb.) ) 1940;.
Bennett, H. G.; Biskind, Gerson, and Mark, Jerome:  Subcutaneous Implantation of Compressed Crystalline Theelin Pellets in the Treatment of Menopausal Cases , Am. J. Obst. & Gynec. 39:504 ( (March) ) 1940;.
Lyons, W. R., and Templeton, H. J.:  Intravaginal Assay of Urinary Estrin , Proc. Soc. Exper. Biol. & Med. 33:587 ( (Jan.) ) 1936;.
Selye, Hans:  On the Toxicity of Oestrogens with Special Reference to Stilbestrol , Canad. M. A. J. 41:48 ( (July) ) 1939;.
Shorr, Ephraim; Robinson, F. H., and Papanicolaou, G. N.:  A Clinical Study of the Synthetic Estrogen Stilbestrol , J. A. M. A. 113:2312 ( (Dec. 23) ) 1939;.
 Risks of Estrogens , editorial, Lancet 1:461 ( (March 9) ) 1940;.
Kurzrok, Raphael; Wilson, Leo, and Perloff, W. H.:  The Action of Diethylstilbestrol in Gynecological Dysfunctions , Endocrinology 26:581 ( (April) ) 1940;.
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To understand the clinical management of acute heart failure syndromes.
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