An attempt to control fetal weight

ARNOLD:

ATTEMPT

TO CONTROL FETAL

WEIGHT

99

The two conditions are found together only rarely. They probably represent two different processeswith some factors in common. REFERENCES und Pathologie des Weibes 4: 160, (1) Adler, L.: In Halban-Seitz : Biologie 1928. (2) AZbrecht, H.: In Halban-Seitz: Biologie und Pathologie des Weibes 4: 269, 1928. (3) Cattell, R. B., a,nd Swinton, N. W.: New England J. Med. 214: 341, 1936. (4) Coulzsellor, V. S.: AM. J. OBST. & GYNEC. 36: 877, 1938. (5) Dougal, D.: Tr. Edinburgh Obst. Sot., p. 61, 1937-1938; AM. J. OBST. & GYNEC. 35: 373, 1938. (6) Franlcl, 0.: Zentralbl. f. GynLk. 56: 902, 1932; Ztschr. Geburtsh. & Gyn%k. 115: 1, 1937. (7) Jeffcoate, T. N. A., and Potter, A. L.: J. Obst. & Gynaee. Brit. Emp. 41: ti84. 1934. (8) Eeene, F. E., and Eimbrough, R. A., Jr.: J. A. M. A. 95: 1164, 1930. (9) King, E. 8. J.: Surg. Gynec. Obst. 53: 22, 1931. (10) Lipschzletz, A., and Vargas, L.: Lancet 236: 1313, 1939. (11) Musson, .7. C.: Ann. Surg. 102: 919, 1933. (12) Meyer, R.: In Veit-Stoeckel: Handbuch cler Gynaekologie 6: Part 1, 356, 1930; In Hencke-Lubarsch: Handbuch der path. Anat. 7: Part 1, 249, 1930. (13) Yorris, J. W.: South. Med. & Surg. 100: 320, g3; 11(.14) Nocnk, E.: AM. J. OBST. & GYKEC. 22: 826, 1931. (15) Nylander, . Zentralbl. f. Chir. 65: 73, 1938. (16) Pemberton, F. .4.: New England J. Med. 217: 1, 1937. (17) Ilockstroh, H.: Zentralbl. f. GynBk. 60: 550, 1936. (18) Sampson, J. -4. : AM. J. OBST. & GYXE~. 24: 497, 1932. (19) Seitz, L.: Arch. f. GynHk. 149: 529, 1932. (20) S’kamnakis, 9. N.: Zentralbl. f. GynHk. 62: 414, 7938. (21) Smith, G. V. S.: Ahf. J. OBST. & GYPJEC.17: 806, 1929. (22) Tzcrunen, il.: Acta obst. et gynec. Scandinav. 18: 237, 1938. (23) T&hill, R. C.: Arch. Surg. 37: 554, 1938. (24) Zaleslii, W.: Zentralbl. f. Gyngk. 60: 1046, 1936.

AN ATTEMPT

TO CONTROL FETAL PRELIMINARY

WEIGHT

REPORT

LAWRENCE E. ARNOLD, M.D., DALLAS, TEXAS (From the Obstetric Service of St. PatiZ’s Hospital)

E

XCLUDIKG prematurity, most neona,tal deaths occur in babies having a birth weight in excess of eight pounds (3,636 gm.). As the fetal birth weight curve rises above eight pounds (3,636 gm.) both the fetal mortality and maternal morbidity curves also rise. The relationship between maternal and fetal weight curves has never been clearly established; however, it is known that the two curves often fail to coincide, because there are factors which cause elevation of maternal weight without affecting fetal weight, the most common factor being edema. Practically speaking, the maternal weight curve is followed throughout pregnancy to reveal early evidence of toxemia, as manifested by edema. Clinical investigation has proved tha.t maternal weight can usually be controlled by dietary restrictions ; however, these restrictions have no effect upon fetal weight. Realizing that maternal dietary excessesdo not cause fetal obesity, the most reasonable etiologic factor that presents itself is a disturbance in thyroid metabolism. Williams1 states that hypertrophy of the thyroid can be recognized clinically in 65 to 90 per cent of all pregnant women. Before an organ undergoes hypertropby there must first be an increased demand placed upon that organ. In the case of preg-

nancy this increased tlrma11t1 is I)rohably tlue to the l)reseuce of tllc fetus ill utero. If the orya~t is unable to meet, this tlemand by hypertrophy and hyperplasia. N state of drficienq~ or tlec~ol~l~e~isation develops. Oue of tlir inaiiifert;r,tiolis of tltyraid drfieieirc*) is, of ~otlTse, obesity. Patterson, Hunt, and Nicoderuus:r demonstrate(l that in subclinical llypothyrOidisIll during pregnancy the mother abrorhs thyrtrxin from the fetus, producing fet,al hypeThe fetal thproitl t,hen reacts to this drain by undergoing extreme thyroidism. This leads to permanent damage to the gland with hyperplasia and hypertrophy. subsequent clinical thyroid tlisraac later in lift, dependent, of course, upon iodine Ansrlmino amI Hoffmans rrportell a marked insupply and physiologic tlemands. crease in the amount of thyroLl hormone in the circulating hlootl of the mother during pregnancy; the amount increases as gestation progresses. The average amount of thyroxin found in the blood during pregnancy is twenty units to the cubic centimeter, according to these observers. Souled substantiated the findings of Anselrnino and Hoffman and expressed the helirf that the increase in thyroid hormone ix due to au actual physiologic hyprrfunction of the thyroid glaml during pregnancy. Williarurl believes that thyroid defirienc*y results in a defective germ plasm and premature termination of pregnancy; if pregnancy continues, monstrosities result. Rreckenridge” reports abortion, premxturc labor. and fetal death caused b.v thyroid insuf25 cases in wllich there was complete rclif,f following ficiency; his report includes thyroid medication.

With the foregoiq evidence as a fomldatioli, a series of caases was st.arted, based upon the thesis that fetal obesity is tlue to a fetal thyroid deficiencdy ~r~hic~h can be corrected by placing a sufficient saturatioll of thyroid extract ill the fetal blood stream. One hundred and sixteen women have been given thyroid extract orally during four or more months of their pregwncies. Patients recririip less than four months of continuous treatment have Ilot been included in this series. Each patient, received uot less than 3 gr. (0.2 gm.) ~1~1 not more thall 6 gr. (0.4 gm.) claily. Armour’s euteric+ voat,ed I gr. (0.065 gm.) ta.blets were used cm all eases. These patients received 110 other meclieatioii that could influence \veifht aild thr,v were told to eat a llormal. well-balanced diet without clrialitative 01’ cluaiititatire footL restric6oii. They were given HO extradietary calcium or vitamins. These women were sern at intervals of note less than two weeks at which time routine prenatal pare was’ given; ii1 adtlition, they were carefnlly examined for evide1ic.r of ~ivl-,ertlir-roitlislu. The fact that these signs failed to develop in a single case is significant and fllrther proves clinically that there is a thyroid deficienc2.v during prepaanc*p : if 116 normal, nonpregnant womeu would be give11 from 3 to 6 gr. (0.2 to 0.4 gm.) of potent thyroid estract daily over a period of four or more rnoiit~hs mally of them would clewlop signs of ltypertli~roidism. Brown”7 made two very comprehensive reports on the administration of thyroid extract during pregnancy ; he was one of the first, workers to discover the extreme variability of potency of the various Uryroid preparations on the market. Da&s selecting a single product of known high potency agrees wrth Brown ; he advises and giving it continuously to all patients throughout pregnancy. He further advises beginning the administration of thyroid extract prior to the pregnancv to avoid xhorCons and fetal maldevelopments. Mussey and Hairtess advise giving a standard

ARNOLD

:

ATTEMPT

TO

CONTROL

FETAL’

WEIGHT

101

brand of desiccated thyroid in doses of about 4 gr. (0.24 gm.) daily for three or four days and then dropping to a maintenance dose of 1 to 2 gr. (0.065 to 0.12 gm.) daily.

Basal rates were done on the first 56 cases; the average rate of this group at an average t,ime of four mont,hs’ gestation was plus, 2 per cent ; the average rate after three months of treatment was plus 22 per cent. Basal rates mere discontinued when it was discovered that an elevated rate is normal during the latter half of pregnancay. Williamsl states that there is a definite elevation in the basal metabolic rate (luring the latter half of pregnancy, due to the presence of the fetus in utero. It returns to normal about the tenth post-pa&urn day. Sandiford and Wheeler10 found that the state of pregnancy demands increased secretion of thyroid extract because of the presence of an increasing mass of active protoplasmic tissue, consisting largely of the fetal tissues and partly of an increase in maternal structures incident to

pregnancy. but found Plummrr, the latter thyroidism. and fail test with be accepted deficiency

They found no change in the basal rate in the early months of pregnancy, a distinct rke and Boothbyll

half

to plus 20 or plus 25 per cent in the final trimester. Mussey, found that basal rates of plus 25 to plus 30 per cent during

of pregnancy

do not necewarily

Daviss pointed out the fact that, to give a true picture of thyroid the administration of desiccated at present. From the foregoing can exist during pregnancy despite

indicate

the presence of hyper-

basal rates in pregnancay are confusing function. He helieves that a clinical thyroid is the only method tvhich can evidence it was concluded that thyroid the presence of a normal basal rat?.

The average maternal weight gain durin g entire pregnancy in this group of 116 cases was 18.2 pounds (8.3 kilograms). The average fetal birth weight was 6.8 pounds (3,090 gm.). There was no fetal mortality or prematurity and no maternal mortality. These weights are not spectacular but they are fairly satisfactory since there were no qualitative or quantitative food restrictions. The most gratifying point in this series is the fact, that no baby weighed more than 7 pounds 12 ounces (3,522 am.) and none less’than 5 pounds 11 ounces (2,590 gm.). Because of the small size of these babies and the fact that no more than 6 gr. (0.4 gm.) of nembutal were used for analgesia in a single case, it was necessary to apply forceps in only twelve instances. Eleven of these were applied below the spines and one in the midplane; this was the largest baby in the group and weighed 7 pounds 12 ounces (3,523 gm.) ; the mother had a justominor pelvis with an anteropost,erior diameter of 10 cm. and a biischial diameter of 8 cm. It. has been suggested recently that thyroid deficiency might play some part in the etiology of the toxemias of pregnancy. Patterson, Hunt, and Nicodemns l2 demonstrated both clinically and experimentally that the increased metabolism of pregnancy produces a subclinical hypothyroidism, which is accompanied by hypercholesteremia. When the maternal thyroid cannot produce sufficient thyroxin t,he fetal thyroid is drained; this constant depletion of fetal thyroxin produces a fetal hypothyroidism and hypercholesteremia. Fetal hypercholesteremia arteries, arterial

causes the deposition of cholesterin in the malls of the placental producing an enclarteritis. Tf the endarteritis is severe,. the lumen mill be occluded, resultin g in placental infarction and

One hundred and sixteen women were given daily doses of from 3 to 6 gr. (0.2 to 0.4 gm.) of tlesiccated thyroid extract during four 01 more months of their pregnancies wit,hout qualitative or quantitative food restrictions. One hundred and sixteen normal babies having an average birth weight of 6.8 pounds (3,090 gm.) were delivered. The mothers demonstrated no signs of hyperthyroidism. pre-eelampsia, 01 eclampsia, and they gained an average of 18.2 pounds (8.3 kilograms) during their pregnancies. (‘ON;(‘I,USIONS

This series is too small to reach any final decision regarding the merits of this treatment ; however, the results to date are encouraging and merit. further study by those who might be interested. (1) Williams, J. W. : Obstetrics, ed. 7, Neu- York, 1936, D. Appleton-Century Co., p. 225. (2) Patterson, W. B., Hunt, H. F., and Nicodemw, R. E.: West. J. Surg. 44: 486, 1937. (3) Anselmino, E., and Hoffman, F.: Arch. f. Gyniik. 143: 310, 1930. (4) Soule, S. D.: AM. J. OBST. & GYNEC. 23: 165, 1932. (5) &-e&enridge, S. D.: Ibid. 23: 871, 1932. (6) Brown, C. F.: Texas State J. Med. 26: Ibid. 31: 287, 1935. (8) Davis, C. H.: AK J. OBST. 406, 1931). (7) Brown. C. F.: & GYNEC. 30: 570, 1935. (9) Mussey, R. D., and Haines. S. F.: Ibid. 27: 404, 1934. (10) Sandiford, Irene, and Wheeler. Theodora: J. Biol. Chem. 62: 329, 1924. (11) Massey, R. D., Pkmmer, W. A., and Boothby, W. 2.: J. A. M. A. 87: 1009, 1926. (12) Patterson, W. B., Huullt, H. F.. and Nicodemus, R. R.: Ani. J. Clin. Path. 8: 120, 1938.

TREATMENT OF METROMENORRHAGIA TESTOSTERONE PROPIONATK A

X’RELIMINARY

WITH

REPORT

W. C. STURGIS, LB., M.D., BALTIMOR~E, &t~., A. R. ABARBANEL, A.B., M.D.. NEW YOR,K, N. Y., AND D. S. NADE,R, PKB., M.D., BOGATA, COLOMBIA, S. (From

T

the

Departm.ent

of Gynecology,

Johns

Hopkins

A.

Unicersity)

HE purpose of this report is to present our experiences with the use of testosterone propionate in the treatment of metromenorrhagia. Here we are particularly concerned with the average minimal dosage necessary to control the excessive bleeding. The therapeutic rationale for the use of testosterone propionate will be fully reviewed e1sewhere.l Briefly summarized, the following conThe effects of testosterone on the endosiderations appear pertinent. metrium are variable. A progestational response may be elicited, for example, in the rabbit,2 but apparently not in the monkey3 or human being.4 Hypoplasia of the endometrium may result from chronic in-