Gene- and Environment-Dependent Neuroendocrine Etiogenesis of Homosexuality and Transsexualism

Abstract

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A (A = androstenedione) ratio were increased before and after ACTH stimulation. Furthermore, highly significantly increased basal plasma levels of dehydroepiandrosterone sulfate were found in male-to-female transsexuals as compared to normal males, suggesting partial 3 beta-ol hydroxysteroid dehydrogenase deficiency to be a predisposing factor for the development of male-to-female transsexualism.

A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism

“…Because the CYP17 TÀ34C SNP is a gain of function mutation, carriers of the mutant C allele have higher serum and tissue concentrations of both testosterone and E 2 (10). The association between the CYP17 TÀ34C SNP T allele and FtM transsexualism is therefore compatible with the hypothesis that increased tissue availability of both testosterone and E 2 leads to an aberration of early brain development regarding central sex differentiation (5,15,16).…”

Biology and the Future of Psychoanalysis: A New Intellectual Framework for Psychiatry Revisited

“…Another question that is now being addressed is whether sexual orientation is inherited or acquired (109)(110)(111)(112)(113)(114)(115). Sexual orientation seems to be influenced by genes, and this influence is, as one would expect, complex.…”

Knowledge of and Attitude Toward Transsexualism Among College Students

“…Biological causes, mainly neurophysiologic, endocrinologic and genetic factors, and psychological causes connected with family environment and transsexual personality have been suggested [13]. Dorner et al [14] notice the influence of androgen levels on brain organization during prenatal period. Zhou et al [15] observe differences in size of the bed nucleus of the stria terminals (BSTc), which in transsexual men are similar in size to BSTc in women.…”

“…Interdisciplinary and multifaceted character of transsexualism is reflected in studies and publications on this phenomenon [1,13,14,20,22,26]. Medical literature largely focuses on the issues of etiology, methods and treatment results, transsexual persons characteristic and legal aspects, however, there are very few publications referring to awareness and approach of the society to this problem [27][28][29][30].…”