Abstract
46,XX individuals with classical congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme, 21-hydroxylase, show variable degrees of masculinization of body and behavior due to excess adrenal androgen production. Increased bisexuality and homosexuality have also been reported. This article provides a review of existing reports of the latter and presents a new study aimed at replicating the previous findings with detailed assessments of sexual orientation on relatively large samples, and at extending the investigation to the mildest form, non-classical (NC) CAH. Also, this is the first study to relate sexual orientation to the specific molecular genotypes of CAH. In the present study, 40 salt-wasters (SW), 21 SV (simple-virilizing), 82 NC, and 24 non-CAH control women (sisters and female cousins of CAH women) were blindly administered the Sexual Behavior Assessment Schedule (SEBAS-A, 1983 ed.; H. F. L. Meyer-Bahlburg & A. A. Ehrhardt, Privately printed). Most women were heterosexual, but the rates of bisexual and homosexual orientation were increased above controls not only in women with classical CAH, but also in NC women, and correlated with the degree of prenatal androgenization. Classifying women by molecular genotypes did not further increase the correlation. Diverse aspects of sexual orientation were highly intercorrelated, and principal components analysis yielded one general factor. Bisexual/homosexual orientation was (modestly) correlated with global measures of masculinization of non-sexual behavior and predicted independently by the degree of both prenatal androgenization and masculinization of childhood behavior. We conclude that the findings support a sexual-differentiation perspective involving prenatal androgens on the development of sexual orientation.
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References
Arnold, A. P. (2002). Concepts of genetic and hormonal induction of vertebrate sexual differentiation in the twentieth century, with special reference to the brain. In D. W. Pfaff, A. P. Arnold, A. M. Etgen, S. E. Fahrbach, & R. T. Rubin (Eds.), Hormones, brain, and behavior (Vol. 4, pp. 105–135). Amsterdam: Academic Press (Elsevier Science).
Arnold, A. P. (2004). Sex chromosomes and brain gender. Nature Reviews Neuroscience, 5, 701–708.
Baum, M. J. (2006). Mammalian animal models of psychosexual differentiation: When is ‘translation’ to the human situation possible? Hormones and Behavior, 50, 579–588.
Bearman, P. S., & Brückner, H. (2002). Opposite-sex twins and adolescent same-sex attraction. American Journal of Sociology, 107, 1179–1205.
Beatty, W. W. (1979). Gonadal hormones and sex differences in nonreproductive behaviors in rodents: Organizational and activational influences. Hormones & Behavior, 12, 112–163.
Blanchard, R. (2004). Quantitative and theoretical analyses of the relation between older brothers and homosexuality in men. Journal of Theoretical Biology, 230, 173–187.
Blanchard, R., & Lippa, R. A. (2007). Birth order, sibling sex ratio, handedness, and sexual orientation of male and female participants in a BBC internet research project. Archives of Sexual Behavior, 36, 163–176.
Bocklandt, S., Horvath, S., Vilain, E., & Hamer, D. H. (2006). Extreme skewing of X chromosome inactivation in mothers of homosexual men. Human Genetics, 118, 691–694.
Burks, S. R., Wright, C. L., & McCarthy, M. M. (2007). Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience, 146, 1117–1127.
Carson, D. J., Okuno, A., Lee, P. A., Stetten, G., Didolkar, S. M., & Migeon, C. J. (1982). Amniotic fluid steroid levels. Fetuses with adrenal hyperplasia, 46,XXY fetuses, and normal fetuses. American Journal of Diseases of Children, 136, 218–222.
Dittmann, R. W., Kappes, M. E., & Kappes, M. H. (1992). Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia. Psychoneuroendocrinology, 17, 153–170.
Dörner, G. (1976). Hormones and brain differentiation. Amsterdam: Elsevier/North-Holland Biomedical Press.
Ehrhardt, A. A. (1979). Psychosocial adjustment in adolescence in patients with congenital abnormalities of their sex organs. In H. L. Vallet & I. H. Porter (Eds.), Genetic mechanisms of sexual development (pp. 473–483). New York: Academic Press.
Ehrhardt, A. A., Evers, K., & Money, J. (1968). Influence of androgen and some aspects of sexually dimorphic behavior in women with the late-treated adrenogenital syndrome. Johns Hopkins Medical Journal, 123, 115–122.
Ellis, L., & Ames, M. A. (1987). Neurohormonal functioning and sexual orientation: A theory of homosexuality–heterosexuality. Psychological Bulletin, 101, 233–258.
Fleming, A., & Vilain, E. (2005). The endless quest for sex determination genes. Clinical Genetics, 67, 15–25.
Gastaud, F., Bouvattier, C., Duranteau, L., Brauner, R., Thibaud, E., Kutten, F., et al. (2007). Impaired sexual and reproductive outcomes in women with classical forms of congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism, 92, 1391–1396.
Gatewood, J. D., Wills, A., Shetty, S., Xu, J., Arnold, A. P., Burgoyne, P. S., et al. (2006). Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice. Journal of Neuroscience, 26, 2335–2342.
Gavrilets, S., & Rice, W. R. (2006). Genetic models of homosexuality: Generating testable predictions. Proceedings of the Royal Society B, 273, 3031–3038.
Grumbach, M. M., Hughes, I. A., & Conte, F. A. (2003). Disorders of sex differentiation. In P. R. Larsen, H. M. Kronenberg, S. Melmed, & K. S. Polonsky (Eds.), Williams textbook of endocrinology (10th ed., pp. 842–1002). Philadelphia: W. B. Saunders.
Guth, L. J., Witchel, R. I., Witchel, S. F., & Lee, P. A. (2006). Relationships, sexuality, gender identity, gender roles, and self-concept of individuals who have congenital adrenal hyperplasia: A qualitative investigation. Journal of Gay & Lesbian Psychotherapy, 10, 57–75.
Hamer, D., & Copeland, P. (1994). The science of desire: The search for the gay gene and biology of behavior. New York: Simon & Schuster.
Hamer, D. H., Hu, S., Magnuson, V. L., Hu, N., & Pattatucci, A. M. L. (1993). A linkage between DNA markers on the X-chromosome and male sexual orientation. Science, 261, 321–327.
Hines, M. (2004). Brain gender. New York: Oxford University Press.
Hines, M., Brook, C., & Conway, G. S. (2004). Androgen and psychosexual development: Core gender identity, sexual orientation, and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH). Journal of Sex Research, 41, 75–81.
Hirschfeld, M. (1906). Vom Wesen der Liebe. Zugleich ein Beitrag zur Lösung der Frage der Bisexualität. Jahrbuch für Sexuelle Zwischenstufen, 8, 1–284.
Horn, P. (1997). Sexualverhalten, psychosexuelle Orientierung und Orgasmuserleben junger Frauen mit kongenitalem adrenogenitalem Syndrome. Unpublished doctoral thesis, Universität Leipzig, Leipzig.
Johannsen, T. H., Ripa, C. P. L., Mortensen, E. L., & Main, K. M. (2006). Quality of life in 70 women with disorders of sex development. European Journal of Endocrinology, 155, 877–885.
Kazdin, A. E. (2002). Research design in clinical psychology (4th ed.). Boston: Allyn & Bacon.
Kennedy, H. (1988). Ulrichs: The life and works of Karl Heinrich Ulrichs, pioneer of the modern gay movement. Boston: Alyson Publications.
Kinsey, A. C., Pomeroy, W. B., Martin, C. E., & Gebhard, P. H. (1953). Sexual behavior in the human female. Philadelphia: Saunders.
Kühnle, U., Bullinger, M., & Schwarz, H. P. (1995). The quality of life in adult female patients with congenital adrenal hyperplasia: A comprehensive study of the impact of genital malformation and chronic disease on female patients’ life. European Journal of Pediatrics, 154, 708–716.
Lalumière, M. L., Blanchard, R., & Zucker, K. J. (2000). Sexual orientation and handedness in men and women: A meta-analysis. Psychological Bulletin, 126, 575–592.
Lev-Ran, A. (1974). Sexuality and educational levels of women with the late-treated adrenogenital syndrome. Archives of Sexual Behavior, 3, 27–32.
Lippa, R. A. (2005). Sexual orientation and personality. Annual Review of Sex Research, 16, 119–153.
Manning, J. T. (2002). Digit ratio: A pointer to fertility, behavior and health. New Brunswick, NJ: Rutgers University Press.
Manning, J. T., Churchill, A. J. G, & Peters, M. (2007). The effects of sex, ethnicity, and sexual orientation on self-measured digit ratio (2D:4D). Archives of Sexual Behavior, 36, 223–233.
May, B., Boyle, M., & Grant, D. (1996). A comparative study of sexual experiences: Women with diabetes and women with congenital adrenal hyperplasia. Journal of Health Psychology, 1, 479–492.
McFadden, D. (2002). Masculinization effects in the auditory systems. Archives of Sexual Behavior, 31, 99–111.
Meyer-Bahlburg, H. F. L. (1977). Sex hormones and male homosexuality in comparative perspective. Archives of Sexual Behavior, 6, 297–325.
Meyer-Bahlburg, H. F. L. (1979). Sex hormones and female homosexuality: A critical examination. Archives of Sexual Behavior, 8, 101–119.
Meyer-Bahlburg, H. F. L., Dolezal, C., Baker, S. W., Ehrhardt, A. A., & New, M. I. (2006). Gender development in women with congenital adrenal hyperplasia as a function of disorder severity. Archives of Sexual Behavior, 35, 667–684.
Meyer-Bahlburg, H. F. L., Ehrhardt, A. A., Rosen, L. R., Gruen, R. S., Veridiano, N. P., Vann, F. H., et al. (1995). Prenatal estrogens and the development of homosexual orientation. Developmental Psychology, 31, 12–21.
Meyer-Bahlburg, H. F. L., Gruen, R. S., New, M. I., Bell, J. J., Morishima, A., Shimshi, M., et al. (1996). Gender change from female to male in classical congenital adrenal hyperplasia. Hormones and Behavior, 30, 319–332.
Miller, E. M. (2000). Homosexuality, birth order, and evolution: Toward an equilibrium reproductive economics of homosexuality. Archives of Sexual Behavior, 29, 1–34.
Money, J., Schwartz, M., & Lewis, V. G. (1984). Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46,XX congenital virilizing adrenal hyperplasia and 46,XY androgen-insensitivity syndrome compared. Psychoneuroendocrinology, 9, 405–414.
Morgan, J. F., Murphy, H., Lacey, J. H., & Conway, G. (2005). Long term psychological outcome for women with congenital adrenal hyperplasia: Cross sectional survey. British Medical Journal, 330, 340–341.
Mulaikal, R. M., Migeon, C. J., & Rock, J. A. (1987). Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. New England Journal of Medicine, 316, 178–182.
Müller, M., Bidlingmaier, F., Förster, C., & Knorr, D. (1982). Psychosexuelles Verhalten von Frauen mit adrenogenitalem Syndrom. Helvetica Paediatrica Acta, 37, 571–580.
Mustanski, B. S., DuPree, M. G., Nievergelt, C. M., Bocklandt, S., Schork, N. J., & Hamer, D. H. (2005). A genomewide scan of male sexual orientation. Human Genetics, 116, 272–278.
Pang, S., Levine, L. S., Cederqvist, L. L., Fuentes, M., Riccardi, V. M., Holcombe J. H., et al. (1980). Amniotic fluid concentrations of delta 5 and delta 4 steroids in fetuses with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and in anencephalic fetuses. Journal of Clinical Endocrinology and Metabolism, 51, 223–229.
Pang, S., Levine, L. S., Chow, D. M., Faiman, C., & New, M. I. (1979). Serum androgen concentrations in neonates and young infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clinical Endocrinology, 11, 575–584.
Pang, S., Pollack, M. S., Loo, M., Green, O., Nussbaum, R., Clayton, G., et al. (1985). Pitfalls of prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism, 61, 89–97.
Pfaus, J. G., Kippin, T. E., & Coria-Avila, G. (2003). What can animal models tell us about human sexual response? Annual Review of Sex Research, 14, 1–63.
Pillard, R. C., & Bailey, J. M. (1998). Human sexual orientation has a heritable component. Human Biology, 70, 347–365.
Pillard, R. C., Rosen, L. R., Meyer-Bahlburg, H. F. L., Weinrich, J. M., Feldman, J. F., Gruen, R. S., & Ehrhardt, A. A. (1993). Psychopathology and social functioning in men prenatally exposed to diethylstilbestrol (DES). Psychosomatic Medicine, 55, 485–491.
Rahman, Q. (2005). Fluctuating asymmetry, second to fourth finger length ratios and human sexual orientation. Psychoneuroendocrinology, 30, 382–391.
Rahman, Q., & Wilson, G. D. (2003). Born gay? The psychobiology of human sexual orientation. Personality and Individual Differences, 34, 1337–1382.
Rice, G., Anderson, C. A., Risch, N., & Ebers, G. (1999). Male homosexuality: Absence of linkage to microsatellite markers at Xq28. Science, 284, 665–667.
Slijper, F. M. E., van der Kamp H. J., Brandenburg, H., de Muinck Keizer-Schrama S. M. P. F., Drop, S. L. S., & Molenaar, J. C. (1992). Evaluation of psychosexual development of young women with CAH: A pilot study. In W. Bezemer, P. Cohen-Kettenis, K. Slob, & N. van Son-Schoones (Eds.), Sex matters (pp. 47–50). Amsterdam: Elsevier Science Publishers B.V.
Sommer V., & Vasey P. L. (Eds.). (2006). Homosexual behavior in animals. An evolutionary perspective. Cambridge: Cambridge University Press.
Stikkelbroeck, N. M. M. L., Beerendonk, C. C. M., Willemsen, W. N. P., Schreuders-Bais, C. A., Feitz, W. F. J., Rieu, P. N. M. A., et al. (2003). The long term outcome of feminizing genital surgery for congenital adrenal hyperplasia: Anatomical, functional and cosmetic outcomes, psychosexual development, and satisfaction in adult female patients. Journal of Pediatric and Adolescent Gynecology, 16, 289–296.
Todd, B. J., Schwarz, J. M., & McCarthy, M. M. (2005). Prostaglandin-E2: A point of divergence in estradiol-mediated sexual differentiation. Hormones and Behavior, 48, 512–521.
Todd, B. J., Schwarz, J. M., Mong, J. A., & McCarthy, M. M. (2007). Glutamate AMPA/kainate receptors, not GABAA receptors, mediate estradiol-induced sex differences in the hypothalamus. Developmental Neurobiology, 67, 304–315.
Wallen, K., & Baum, M. J. (2002). Masculinization and defeminization in altricial and precocial mammals: Comparative aspects of steroid hormone action. In D. W. Pfaff, A. P. Arnold, A. M. Etgen, S. E. Fahrbach, & R. T. Rubin (Eds.), Hormones, brain, and behavior (Vol. 4. pp. 385–423). Amsterdam: Academic Press (Elsevier Science).
White, P. C., & Speiser, P. W. (2000). Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocrine Reviews, 21, 245–291.
Wudy, S. A., Dörr, H. G., Solleder, C., Djalali, M., & Homoki, J. (1999). Profiling steroid hormones in amniotic fluid of midpregnancy by routine stable isotope dilution/gas chromatography-mass spectrometry: Reference values and concentrations in fetuses at risk for 21-hydroxylase deficiency. Journal of Clinical Endocrinology & Metabolism, 84, 2724–2728.
Zehr, J. L., Todd, B. J., Schulz, K. M., McCarthy, M. M., & Sisk, C. L. (2006). Dendritic pruning of the medial amygdala during pubertal development of the male Syrian hamster. Journal of Neurobiology, 66, 578–590.
Zucker, K. J., & Bradley, S. J. (1995). Gender identity disorder and psychosexual problems in children and adolescents. New York: Guilford Press.
Zucker, K. J., Bradley, S. J., Oliver, G., Blake, J., Fleming, S., & Hood, J. (1996). Psychosexual development of women with congenital adrenal hyperplasia. Hormones and Behavior, 30, 300–318.
Acknowledgments
The project described was supported in part by USPHS Grants HD-38409, RR06020 (GCRC), and by Grant Number U54 RR01-9484 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibilities of the authors and do not necessarily represent the official views of NCRR or NIH. We thank the study women for their participation in this research. Ms. Rhoda Gruen served as interviewer trainer. Ms. Patricia Connolly assisted in word processing.
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Meyer-Bahlburg, H.F.L., Dolezal, C., Baker, S.W. et al. Sexual Orientation in Women with Classical or Non-classical Congenital Adrenal Hyperplasia as a Function of Degree of Prenatal Androgen Excess. Arch Sex Behav 37, 85–99 (2008). https://doi.org/10.1007/s10508-007-9265-1
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DOI: https://doi.org/10.1007/s10508-007-9265-1