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Prenatal exposure to synthetic progestins and estrogens: Effects on human development

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Abstract

Seventy-one offspring of mothers administered combinations of synthetic progestins and estrogen for the maintenance of at-risk pregnancy were evaluated for their performance on IQ and personality tests. Siblings born of untreated pregnancies acted as controls. Hormone-exposed subjects were partitioned into three treatment subgroups dependent on the ratio of progestin to estrogen administered to their mothers during pregnancy. No difference in IQ was obtained among the three treatment subgroups even when scores were adjusted for sibling score and prenatal and perinatal complications. Responses to the personality questionnaire provided significant differences among the three groups. The group exposed to the progestin regime (progestin alone or in combination with very low doses of estrogen) and the estrogen regime (higher doses of estrogen than progestin) were most dissimilar. Progestin regime exposed subjects were characterized as more independent, sensitive, self-assured, individualistic, and self-sufficient. In contrast, the subjects exposed to the estrogen regime were more group oriented and group dependent. Analysis of difference scores generated by subtracting the score of an unexposed sibling from that of the exposed cosibling provided similar results. A general discussion is presented on the efficacy of hormone treatment for pregnancy maintenance, augmented fetal wastage of males, birth order and treatment, maternal knowledge of treatment and its possible postnatal effects on the offspring, and drug effects on the fetus.

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References

  • Aarskog, D. (1970). Clinical and cytogenetic studies in hypospadias.Acta Paediat. Scand. 203: 1.

    Google Scholar 

  • Baker, S. W., and Ehrhardt, A. A. (1974). Prenatal androgen, intelligence and cognitive sex differences. In Friedman, R. C., Richart, R. N., and Vande Wiele, R. L. (eds.),Sex Differences in Behavior Wiley, New York, pp. 53–84.

    Google Scholar 

  • Baker, D. J., and Edwards, J. H (1967). Obstetric complications and school performance.Br. Med. J. ii: 695–699.

    Google Scholar 

  • Bongiovanni, M., DiGeorge, M., and Grumbach, M. M. (1959). Masculinization of the female infant associated with estrogenic therapy alone during gestation: Four cases.J. Clin. Endocrinol. 189: 1004–1011.

    Google Scholar 

  • Burstein, R., and Wasserman, H. C. (1964). The effect of provera on the fetus.Obstet. Gynecol. 23: 931–934.

    PubMed  Google Scholar 

  • Cattell, R. B., Eber, H. W., and Tatsuoka, M. M. (1970).Handbook for the Sixteen Personality Factor Questionnaire Institute for Personality and Ability Testing, Champaign, Ill., 388 pp.

    Google Scholar 

  • Cohen, J. (1957). A factor-analytically based rationale for the Wechsler Adult Intelligence Scale.J. Consult. Psychol. 21: 451–457.

    PubMed  Google Scholar 

  • Cohen, J. (1959). The factorial structure of the WISC at ages 7-6, 10-6, and 13-6.J. Consult. Psychol. 23: 285–299.

    Google Scholar 

  • Conrad, H. S., and Jones, H. E. (1940). A second study of familial resemblance in intelligence: Environmental and genetic implications of parent-child and sibling correlations in the total sample.The 39th Yearbook: Intelligence, Its Nature and Nurture: National Society for the Study of Education 39(II): 97–141.

    Google Scholar 

  • Courrier, R., and Jost, A. (1942). Intersexualite foetale provoquee par la pregneninolone au cours de la grossesse.Soc. Biol. (Paris) 136: 395–396.

    Google Scholar 

  • Dalton, K. (1968). Ante-natal progesterone and intelligence.Br. J. Psychiat. 144: 1377–1383.

    Google Scholar 

  • Dalton, K. (1976). Prenatal progesterone and educational attainments.Br. J. Psychiat. 129: 438–442.

    Google Scholar 

  • Diamond, M., Llacuna, A., and Wond, C. L. (1973). Sex behavior after neonatal progesterone, testosterone, estrogen, or antiandrogens.Horm. Behav. 4: 73–88.

    Google Scholar 

  • Duncan, D. B. (1955). Multiple range and multipleF tests.Biometrics 11: 1–42.

    Google Scholar 

  • Ehrhardt, A. A. (1973). Maternalism in fetal hormonal and related syndromes. In Zubin, J., and Money, J. (eds.),Contemporary Sexual Behavior: Critical issues in the 1970s Johns Hopkins University Press, Baltimore, pp. 91–105.

    Google Scholar 

  • Ehrhardt, A. A., and Baker, S. W. (1974). Fetal androgens, human central nervous system differentiation, and behavior sex differences. In Friedman, R. C., Richart, R. M., and Vande Wiele, R. L. (eds.),Sex Differences in Behavior Wiley, New York, pp. 33–51.

    Google Scholar 

  • Ehrhardt, A. A., and Money, J. (1967). Progestin-induced hermaphroditism: I. Q. and psychosexual identity in a study of ten girls.J. Sex Res. 3: 83–100.

    Google Scholar 

  • Ehrhardt, A. A., Epstein, R., and Money, J. (1968a). Fetal androgens and female gender identity in the early-treated adrenogenital syndrome.Johns Hopkins Med. J. 122: 160–167.

    PubMed  Google Scholar 

  • Ehrhardt, A. A., Evers, K., and Money, J. (1968b). Influence of androgen and some aspects of sexually dimorphic behavior in women with late-treated adrenogenital syndrome.Johns Hopkins Med. J. 123: 115–122.

    PubMed  Google Scholar 

  • Ehrhardt, A. A., Greenberg, N., and Money, J. (1970). Female gender identity and absence of fetal gonadal hormones: Turner's syndrome.Johns Hopkins Med. J. 126: 237–248.

    PubMed  Google Scholar 

  • Erlenmeyer-Kimling, L., and Jarvik, L. F. (1963). Genetics and intelligence: A review.Science 142: 77–78.

    Google Scholar 

  • Fine, E. H., Levin, M., and McConnell, E. L. (1963). Masculinization of female infants associated with norethindrome acetate.Obstet. Gynecol. 22: 210–213.

    PubMed  Google Scholar 

  • Forfar, J. O., and Nelson, M. M. (1973). Epidemiology of drugs taken by pregnant women: Drugs that may affect the fetus adversely.Clin. Pharmacol. Ther. 14(2): 632–642.

    PubMed  Google Scholar 

  • Fuchs, F., and Stakeman, G. (1960). Treatment of threatened premature labor with large doses of progesterone.Am. J. Obstet. Gynecol. 79: 172–176.

    PubMed  Google Scholar 

  • Gillette, J. R., Menard, R. H., and Stripp, B. (1973). Active products of fetal drug metabolism.Clin. Pharmacol. Ther. 14(2): 680–692.

    PubMed  Google Scholar 

  • Goy, R. W. (1970a). Early hormonal influence on the development of sexual and sex-related behavior. In Quarlon, G. C., Melnechuk, T., and Schmitt, F. O. (eds.),Neurosciences: A Study Program Rockefeller University Press, New York, pp. 196–207.

    Google Scholar 

  • Goy, R. W. (1970b). Experimental control of psychosexuality.Philos. Trans. Roy. Soc. Lond. (Biol.). 259: 149–162.

    Google Scholar 

  • Greene, R. R., Burrill, M. W., and Ivy, A. C. (1939). Progesterone is androgenic.Endocrinology 24: 351–357.

    Google Scholar 

  • Grumbach, M. M., and Ducharme, R. (1960). The effects of androgens on fetal sexual development: Androgen-induced female pseudohermaphroditism.Fertil. Steril. 11: 157–180.

    PubMed  Google Scholar 

  • Grumbach, M. M., Ducharme, R., and Moloshok, R. E. (1959). On the fetal masculinization action of certain oral progestins.J. Clin. Endocrinol. Metab. 19: 1369–1380.

    PubMed  Google Scholar 

  • Hagler, S. A., Schultz, A., Hankin, H., and Kunstadter, R. H. (1963). Fetal effects of steroid therapy during pregnancy.Am. J. Dis. Child. 106: 586–590.

    PubMed  Google Scholar 

  • Hayles, A. B., and Nolan, R. B. (1957). Female pseudohermaphroditism: Report of case in an infant born of a mother receiving methyltestosterone during pregnancy.Proc. Staff Mayo Clin. 32: 41–44.

    Google Scholar 

  • Hayles, A. B., and Nolan, R. B. (1958). Masculinization of female fetus, possibly related to administration of progesterone during pregnancy.Proc. Staff Mayo Clin. 33: 200–203.

    Google Scholar 

  • Heinonen, O. P. (1973). Diethylstilbestrol in pregnancy: Frequency of exposure and usage patterns.Cancer 31: 573–577.

    PubMed  Google Scholar 

  • Hildreth, G. H. (1925). The resemblance of siblings in intelligence and achievement.Teachers Coll. Contrib. Educ. 186: 1–65.

    Google Scholar 

  • Hollingshead, A. B. (1957).Two Factor Index of Social Position privately printed, Yale University, New Haven.

    Google Scholar 

  • Jacobson, D. B. (1961). Abortion: Its prediction and management: clinical experience with norlutin.Fertil. Steril. 12: 474–485.

    PubMed  Google Scholar 

  • Jones, H. W., and Wilkins, L. (1960). The genital anomaly associated with prenatal exposure to progestogens.Fertil. Steril. 11: 148–156.

    PubMed  Google Scholar 

  • Jost, A. (1973). Hormonal effects on fetal development: A survey.Clin Pharmacol. Ther. 14: 714–720.

    PubMed  Google Scholar 

  • Kaplan, N. M. (1959). Male pseudohermaphroditism: Report of a case with observation of pathogenesis.New Engl. J. Med. 261: 641–644.

    PubMed  Google Scholar 

  • Lanier, A. P., Noller, K. L., Decker, D. G., Elveback, L. R., and Kurland, L. T. (1973). Cancer and stilbestrol: A follow-up of 1,719 persons exposed to estrogensin utero and born 1943–1959.Mayo Clin. Proc. 48: 793–799.

    PubMed  Google Scholar 

  • Lerner, L. J., Philippo, M., Yiacs, E., Brennan, D., and Borman, A. (1962). Comparison of the acetophenone derivatives of 16–17-dihydroxyprogesterone with other progestational steroids for masculinization of the rat fetus.Endocrinology 71: 448–451.

    PubMed  Google Scholar 

  • Lewis, V. G., Money J., and Epstein, R. (1968). Concordance of verbal and nonverbal ability in the adrenogenital syndrome.Johns Hopkins Med. J. 122: 192–195.

    PubMed  Google Scholar 

  • Masica, D. N., Money, J., Ehrhardt, A. A., and Lewis, V. G. (1969). I. Q., fetal sex hormones and cognitive patterns: Studies in testicular feminizing syndrome of androgen insensitivity.Johns Hopkins Med. J. 124: 34–43.

    PubMed  Google Scholar 

  • Maxwell, J., and Pilliner, A. E. (1960). The intellectual resemblance between sibs.Ann. Hum. Genet. 24: 23–32.

    Google Scholar 

  • Mirkin, B. L. (1973). Maternal and fetal distribution of drugs in pregnancy.Clin Pharmacol. Ther. 14(2): 643–647.

    PubMed  Google Scholar 

  • Møller, K. J., and Fuchs, F. (1965). Double-blind controlled trial of 6-methyl, 17-acetoxy-progesterone in threatened abortion.J. Obstet. Gynaecol. Br. Commonw. 72: 1042–1044.

    Google Scholar 

  • Money, J. (1972a). Clinical aspects of prenatal steroidal action on sexually dimorphic behavior. In Sawyer, C., and Gorski, R. A. (eds.)Steroidal Hormones and Brain Function University of California Press, Berkeley, pp. 325–338.

    Google Scholar 

  • Money, J. (1972b). Determinants of human sexual behavior. In Sager, C. J., and Kaplan, H. A. (eds.),Progress in Family and Group Therapy Brunner/Masel, New York.

    Google Scholar 

  • Money, J., and Ehrhardt, A. A. (1968). Prenatal hormonal exposure: Possible effects on behavior in man. In Michael, R. P. (ed.),Endocrinology and Human Behavior Oxford University Press, London, pp. 32–48.

    Google Scholar 

  • Money, J., and Lewis, V. (1966). I.Q., genetic and accelerated growth: adrenogenital syndrome.Bull. Johns Hopkins Hosp. 118: 365–373.

    Google Scholar 

  • Money, J., and Meredith, T. (1967). Elevated verbal IQ and idiopathic precocious sexual maturation.Pediat. Res. 1: 59–65.

    Google Scholar 

  • Money, J., Lewis, V., Ehrhardt, A. A., and Drash, P. W. (1967). I.Q. impairment and elevation in endocrine and related cytogenetic disorders. In Zubin, J. (ed.),Psychopathology of Mental Development Grune and Stratton, New York, pp. 22–27.

    Google Scholar 

  • Money, J., Ehrhardt, A. A., and Masica, D. N. (1968). Fetal feminization induced by androgen insensitivity in the testicular feminization syndrome: effect on marriage and maternalism.Jolms Hopkins Med. J. 123: 105–114.

    Google Scholar 

  • Nalbandov, A. V. (1958). Effect of progesterone on ovarian morphology and on embryonal mortality in pregnant rats, pigs, and sheep.Ann. N.Y. Acad. Sci. 71: 580–587.

    PubMed  Google Scholar 

  • Noller, K. L., and Fish, C. R. (1974). Diethylstilbestrol usage: Its interesting past, important present, and questionable future.Med. Clin. N. Am. 58: 793–810.

    PubMed  Google Scholar 

  • Øvlisen, B., and Iversen, J. (1963). Treatment of threatened premature labor with 6α-methyl-17α-acetoxyprogesterone.Am. J. Obstet. Gynecol. 86: 291–295.

    PubMed  Google Scholar 

  • Piotrowski, J. (1968a). Experimental investigations on the effect of progesterone on embryonal development. II. Investigations carried out on rabbits.Folia Biol. (Krakow) 16: 335–342.

    Google Scholar 

  • Piotrowski, J. (1968b). The effect of progesterone on the foetal development of rats of the Wistar strain. Part III.Folia Biol. (Krakow) 16: 343–353.

    Google Scholar 

  • Reilly, W. A., Hinman, F., Pickering, D. E., and Crane, J. T. (1958). Phallic urethra in female pseudohermaphroditism.AMA J. Dis. Child. 95: 9–17.

    PubMed  Google Scholar 

  • Reinisch, J. M. (1974). Fetal hormones, the brain, and human sex differences: a heuristic integrative review of the literature.Arch. Sex. Behav. 3: 51–90.

    PubMed  Google Scholar 

  • Reinisch, J. M. (1976). Effects of prenatal hormone exposure on physical and psychological development in humans and animals: With a note on the state of the field. In Sachar, E. J. (ed.),Hormones, Behavior and Psychopathology Raven Press, New York, pp. 69–93.

    Google Scholar 

  • Reinisch, J. M. (1977). Prenatal exposure of human foetuses to synthetic progestin and estrogen affects personality.Nature 266: 561–562.

    PubMed  Google Scholar 

  • Revesz, C., Chappel, C. I., and Gaudry, R. (1960). Masculinization of female fetuses in the rat by progestational compounds.Endocrinology 66: 140–144.

    Google Scholar 

  • Roberts, J. F. (1940). Studies on a child population. V. The resemblance in intelligence between sibs.Ann. Eugen. 10: 293–312.

    Google Scholar 

  • Schöler, H. F., and de Wachter, A. M. (1961). Evaluation of androgenic properties of progestational compounds in the rat by the female foetal masculinization test.Acta Endocrinol. (Kbh.) 38: 128–136.

    Google Scholar 

  • Shearman, R. F., and Garrett, W. J. (1963). Double-blind study of effect of 17-hydroxy-progesterone caproate on abortion rate.Br. Med. J. 5326: 292–295.

    PubMed  Google Scholar 

  • Suchowsky, G. R., and Junkmann, K. (1961). A study of the virilizing effect of progestogens on the female rat fetus.Endocrinology 68: 341–349.

    Google Scholar 

  • Thorndike, E. L. (1928). The resemblance of siblings in intelligence.The 27th Yearbook: Nature and Nurture, Their Influence on Intelligence: National Society for the Study of Education 27(I): 41–53.

    Google Scholar 

  • Walker, P. A., and Money, J. (1972). Prenatal androgenization of females.Hormones 3: 119–128.

    PubMed  Google Scholar 

  • Whalen, R. E., Peck, C. K., and Lopiccolo, J. (1966). Virilization of female rats by prentally administered progestin.Endocrinology 78: 965–970.

    PubMed  Google Scholar 

  • Wilkins, L. (1960). Masculinization of female fetus due to use of orally given progestins.J. Am. Med. Assoc. 172: 1028–1032.

    Google Scholar 

  • Wilkins, L., Jones, W., Holman, G., and Stempfel, S. (1958). Masculinization of the female fetus associated with administration of oral and intramuscular progestins during gestation: Non-adrenal female pseudohermaphrodism.J. Clin Endocrinol. Metab. 18: 559–585.

    PubMed  Google Scholar 

  • Yalom, I. D., Green, R., and Fisk, N. (1973). Prenatal exposure to female hormones: Effect on psychosexual development in boys.Arch. Gen. Psychiat. 28: 554–461.

    PubMed  Google Scholar 

  • Zussman, J. U., Zussman, P. P., and Dalton, K. (1975). Post-pubertal effects of prenatal administration of progesterone. Presented at the Society for Research in Child Development, Denver, April.

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Original research was supported by Research Grant No. NE-G-00-3-0106, National Institute of Education, the Ford Foundation, the Erickson Educational Foundation, and Behavioral science Research Grant, U.S. Public Health Service to J. Reinisch.

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Reinisch, J.M., Karow, W.G. Prenatal exposure to synthetic progestins and estrogens: Effects on human development. Arch Sex Behav 6, 257–288 (1977). https://doi.org/10.1007/BF01541201

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