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THE EFFECT OF THEELIN INJECTIONS ON THE CASTRATED WOMAN FREE

AUGUST A. WERNER, M.D.
[+] Author Affiliations

Because of lack of space this article is abbreviated in The Journal by the omission of a chart and the day by day reports of the cases. The complete article appears in the authors' reprints.


JAMA. 1933;100(9):633-640. doi:10.1001/jama.1933.02740090005002
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The object of these experiments was to determine the effect of various dosages of theelin on human female castrates of different ages and varying length periods of castration. It was of particular interest to study the effect of this hormone on the subjective symptoms that accompany castration and on the involutionary changes that occur in the breasts and the genital tract following ovariectomy.

Stockard and Papanicolaou1 described an exact method for following the estrual changes in the living guinea-pig by the vaginal smear. This method has been applied to the correlation of the estrual phenomena in the genital organs of the rat2 and the mouse.3 Allen and Doisy,4 employing ovarian follicle fluid from hogs, produced pubertas praecox in immature albino rats. The vagina of the immature rat is completely closed, its external third being a solid cord of cells. They found that the injection of the

REFERENCES

Stockard, C. R., and Papanicolaou, G. N.:  Existence of a Typical Estrous in the Guinea-Pig, with a Study of Its Histology and Physiological Changes , Am. J. Anat. 22:225 ( (Sept.) ) 1917;.
Long, A. J., and Evans, H. M.: The Estrous Cycle in the Rat and Its Associated Phenomena , Mem. Univ. California, June, 1922;.
Allen, Edgar:  The Estrous Cycle in the Mouse , Am. J. Anat. 30: 297 ( (May) ) 1922;.
Allen, Edgar, and Doisy, E. A.:  The Induction of a Sexually Mature Condition in Immature Females by Injection of the Ovarian Follicle Hormone , Am. J. Physiol. 69:577-588 ( (Aug.) ) 1924;.
Frank, R. T.; Kingery, H. M., and Gustafson, R. G.:  The Female Sex Hormone , J. A. M. A. 85:20 ( (Nov. 14) ) 1925;.
Allen, Edgar, and Doisy, E. A.:  An Ovarian Hormone , J. A. M. A. 81:819 ( (Sept. 8) ) 1923;.
Frank, R. T.: The Female Sex Hormone , Springfield, Ill., C. C. Thomas, 1929;.
Allen, Edgar; Pratt, J. P., and Doisy, E. A.:  The Ovarian Follicular Hormone: Its Distribution in Human Genital Tissues , J. A. M. A. 85: 6 ( (Aug. 8) ) 1925;.
Doisy, E. A.; Thayer, S. A., and Veler, C. D.:  The Crystalline Follicular Hormone , Theelin, J. Biol. Chem. 86:499 ( (April) ) 1930;.
Smith, P. E.:  Ablation and Transplantation of Hypophysis in the Rat , Anat. Rec. 32: 221, 1926;.
Smith, P. E., and Engle, E. T.:  Experimental Evidence Regarding the Rôle of the Anterior Pituitary in the Development and Regulation of the Genital System , Am. J. Anat. 40: 159 ( (Nov.) ) 1927;.
Evans, H. M., and Long, A. J.:  The Effect of Feeding the Anterior Lobe Hypophysis in the Estrus of the Rat and the Effect of the Anterior Lobe Administered Intraperitoneally on Growth, Maturity and Estrous Cycle of the Rat , Anat. Rec. 21:62, 1921;.
There is much question at the present time as to the existence of a separate luteinizing hormone. The generally accepted idea is that there is one anterior lobe sex stimulating hormone which produces sexual development and the premenstrual ovarian phenomena.
Heape, W.: Phil. Tr. Roy. Soc. London 185: 411, 1894;
188: 135, 1897.
Van Herwerden: M. thesis, Utrecht, 1905.
Hartman, C.:  Menstruation Without Ovulation in Macacus Rhesus: Account of an Experiment, abstr. Anat. Rec. 35:13 ( (March) ) 1927;.
Corner, G. W.:  The Relation Between Menstruation and Ovulation in the Monkey , J. A. M. A. 89:22 ( (Nov. 26) ) 1927;.
Allen, Edgar:  The Time of Ovulation in the Menstrual Cycle of the Monkey Macacus Rhesus , Proc. Soc. Exper. Biol. & Med. 23:381-383 ( (Feb.) ) 1926;.
Corner, G. W.: Cont. Embryol. Carnegie Institution , 1923;, numbers (73) and 75.
Allen, Edgar:  Effects of Ovariectomy on Menstruation in Monkeys , Am. J. Physiol. 85:471 ( (July) ) 1928;
Am. J. Anat. 42:467 ( (Nov.) ) 1928;.
Allen, Edgar:  Endocrine Activity of the Ovary , J. A. M. A. 97: 17 ( (Oct. 24) ) 1931;.
Werner, A. A.:  Symptoms Accompanying Ovarian Hypofunction , J. Missouri M. A. 28:363-369 ( (Aug.) ) 1931;.
Correction: Patient 2, aged 40, who was used in the experiments evidently had the uterus removed. This woman had had the laparotomy done by a physician in his private office and was immediately removed to her home. No record was obtainable and no statement could be had from the physician. The patient was not certain as to what organs had been removed. One of the gynecologists who assisted me made an examination of the patient and decided that the uterus had not been removed. Although the supposed uterus was small, and the depth of the cavity, including the cervical canal, by measurement was 1½ inches, or 37.5 mm., long, this was thought to be due to atrophy as a result of the operation. This woman was treated as the other patients were for the first eighty-nine days and for two and one-half months subsequently, but she gave no evidence of menstruation. Tissue obtained from seven curettements done at various times throughout the experiment failed to show any endometrial tissue at any time; in other words, only cervical tissue was found. The foregoing facts lead to the conclusion that patient 2 had the body of the uterus removed and had a long cervical canal. However, since she responded in every way as did the other patients, except as to menstruation, which was impossible, her record will be retained in this article.
A plentiful amount of this hormone was supplied by Parke, Davis & Co.
Robertson, D. C.; Maddux, W. P., and Allen, Edgar:  Ovarian Hormone Effects on Ovariectomized Monkeys , Endocrinology 14: 77 ( (March-April) ) 1930;.
Morrell, J. A.; Powers, H. H.; Verley, J. R., and DeFrates, J.:  The Results of Oral Administration of Amniotin to Monkeys , Endocrinology 14: 174 ( (May-June) ) 1930;.

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Stockard, C. R., and Papanicolaou, G. N.:  Existence of a Typical Estrous in the Guinea-Pig, with a Study of Its Histology and Physiological Changes , Am. J. Anat. 22:225 ( (Sept.) ) 1917;.
Long, A. J., and Evans, H. M.: The Estrous Cycle in the Rat and Its Associated Phenomena , Mem. Univ. California, June, 1922;.
Allen, Edgar:  The Estrous Cycle in the Mouse , Am. J. Anat. 30: 297 ( (May) ) 1922;.
Allen, Edgar, and Doisy, E. A.:  The Induction of a Sexually Mature Condition in Immature Females by Injection of the Ovarian Follicle Hormone , Am. J. Physiol. 69:577-588 ( (Aug.) ) 1924;.
Frank, R. T.; Kingery, H. M., and Gustafson, R. G.:  The Female Sex Hormone , J. A. M. A. 85:20 ( (Nov. 14) ) 1925;.
Allen, Edgar, and Doisy, E. A.:  An Ovarian Hormone , J. A. M. A. 81:819 ( (Sept. 8) ) 1923;.
Frank, R. T.: The Female Sex Hormone , Springfield, Ill., C. C. Thomas, 1929;.
Allen, Edgar; Pratt, J. P., and Doisy, E. A.:  The Ovarian Follicular Hormone: Its Distribution in Human Genital Tissues , J. A. M. A. 85: 6 ( (Aug. 8) ) 1925;.
Doisy, E. A.; Thayer, S. A., and Veler, C. D.:  The Crystalline Follicular Hormone , Theelin, J. Biol. Chem. 86:499 ( (April) ) 1930;.
Smith, P. E.:  Ablation and Transplantation of Hypophysis in the Rat , Anat. Rec. 32: 221, 1926;.
Smith, P. E., and Engle, E. T.:  Experimental Evidence Regarding the Rôle of the Anterior Pituitary in the Development and Regulation of the Genital System , Am. J. Anat. 40: 159 ( (Nov.) ) 1927;.
Evans, H. M., and Long, A. J.:  The Effect of Feeding the Anterior Lobe Hypophysis in the Estrus of the Rat and the Effect of the Anterior Lobe Administered Intraperitoneally on Growth, Maturity and Estrous Cycle of the Rat , Anat. Rec. 21:62, 1921;.
There is much question at the present time as to the existence of a separate luteinizing hormone. The generally accepted idea is that there is one anterior lobe sex stimulating hormone which produces sexual development and the premenstrual ovarian phenomena.
Heape, W.: Phil. Tr. Roy. Soc. London 185: 411, 1894;
188: 135, 1897.
Van Herwerden: M. thesis, Utrecht, 1905.
Hartman, C.:  Menstruation Without Ovulation in Macacus Rhesus: Account of an Experiment, abstr. Anat. Rec. 35:13 ( (March) ) 1927;.
Corner, G. W.:  The Relation Between Menstruation and Ovulation in the Monkey , J. A. M. A. 89:22 ( (Nov. 26) ) 1927;.
Allen, Edgar:  The Time of Ovulation in the Menstrual Cycle of the Monkey Macacus Rhesus , Proc. Soc. Exper. Biol. & Med. 23:381-383 ( (Feb.) ) 1926;.
Corner, G. W.: Cont. Embryol. Carnegie Institution , 1923;, numbers (73) and 75.
Allen, Edgar:  Effects of Ovariectomy on Menstruation in Monkeys , Am. J. Physiol. 85:471 ( (July) ) 1928;
Am. J. Anat. 42:467 ( (Nov.) ) 1928;.
Allen, Edgar:  Endocrine Activity of the Ovary , J. A. M. A. 97: 17 ( (Oct. 24) ) 1931;.
Werner, A. A.:  Symptoms Accompanying Ovarian Hypofunction , J. Missouri M. A. 28:363-369 ( (Aug.) ) 1931;.
Correction: Patient 2, aged 40, who was used in the experiments evidently had the uterus removed. This woman had had the laparotomy done by a physician in his private office and was immediately removed to her home. No record was obtainable and no statement could be had from the physician. The patient was not certain as to what organs had been removed. One of the gynecologists who assisted me made an examination of the patient and decided that the uterus had not been removed. Although the supposed uterus was small, and the depth of the cavity, including the cervical canal, by measurement was 1½ inches, or 37.5 mm., long, this was thought to be due to atrophy as a result of the operation. This woman was treated as the other patients were for the first eighty-nine days and for two and one-half months subsequently, but she gave no evidence of menstruation. Tissue obtained from seven curettements done at various times throughout the experiment failed to show any endometrial tissue at any time; in other words, only cervical tissue was found. The foregoing facts lead to the conclusion that patient 2 had the body of the uterus removed and had a long cervical canal. However, since she responded in every way as did the other patients, except as to menstruation, which was impossible, her record will be retained in this article.
A plentiful amount of this hormone was supplied by Parke, Davis & Co.
Robertson, D. C.; Maddux, W. P., and Allen, Edgar:  Ovarian Hormone Effects on Ovariectomized Monkeys , Endocrinology 14: 77 ( (March-April) ) 1930;.
Morrell, J. A.; Powers, H. H.; Verley, J. R., and DeFrates, J.:  The Results of Oral Administration of Amniotin to Monkeys , Endocrinology 14: 174 ( (May-June) ) 1930;.
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