Neuroendocrine response to estrogen and brain differentiation in heterosexuals, homosexuals, and transsexuals

Abstract

Since 1964, we have found positive estrogen feedback to be a relatively sex-specific reaction of the hypothalamo-hypophyseal system in rats as well as in human beings. It is dependent on the estrogen-convertible androgen level during sexual brain differentiation and also on estrogen priming in adulthood. The lower the estrogen-convertible androgen or primary estrogen level during brain differentiation, the higher the evocability of a positive estrogen action on LH secretion in later life. In clinical studies, we induced a positive estrogen feedback luteinizing hormone secretion in most intact homosexual men, in clear-cut contrast to intact heterosexual or bisexual men. In addition, the evocability of a positive estrogen feedback was also demonstrable in most homosexual male-to-female transsexuals in significant contrast to hetero-or bisexual male-to-female transsexuals. The following relations have been found between sex hormone levels during brain differentiation and sex-specific responses in adulthood: (i) Estrogens, which are mostly converted from androgens, are responsible for the sex-specific organization of gonadotropin secretion and hence the evocability of a positive estrogen feedback in later life; (ii) both estrogens and androgens, occurring during brain differentiation, predetermine sexual orientation, and (iii) androgens, without conversion to estrogens, are responsible for the sex-specific organization of gender role behavior. Furthermore, the organization periods for sex-specific gonadotropin secretion, sexual orientation, and gender role behavior are not identical but overlapping. Thus, combinations as well as dissociations between deviation of the neuroendocrine organization of sex-specific gonadotropin secretion, sexual orientation, and gender role behavior may occur.

Functional neuroanatomy and neuropathology of the human hypothalamus

“…From Hofman and Swaab (1989), with permission disease patients were found to be within the normal range for age and sex (Swaab and Hofman 1988). A prominent theory is that sexual orientation develops as a result of an interaction between the developing brain and sex hormones (Gladue et al 1984;D6rner 1988). According to D6rner's hypothesis, male homosexuals have a female differentiation of the hypothalamus.…”

Click-Evoked Otoacoustic Emissions in Children and Adolescents with Gender Identity Disorder

“…Sexual orientation is thought to be influenced by prenatal biological mechanisms, such as genes and sex steroid actions mediating and affecting the sexual differentiation of the brain (Balthazart, 2011;Dörner, 1988;Williams et al, 2000). McFadden and Pasanen (1998) found significantly weaker CEOAEs in homo-and bisexual women compared to heterosexual women.…”

Changes in LH secretion in response to an estradiol challenge in male- and female-oriented rams and in ewes

“…Thus, these aspects of neuroendocrine function and behavior appear to be defeminized in MORs to the same extent as would be expected in FORs. Although earlier work in humans suggested that homosexual but not heterosexual men are responsive to estrogen feedback (Gladue et al 1984, Dorner 1988, this observation was subsequently refuted (Gooren 2006). Rather, the surge mechanism in humans and nonhuman primates is equally competent in both sexes in contrast to rodents and sheep where it is permanently inhibited (i.e., defeminized) by perinatal exposure to androgens (Karsch et al 1973, Karsch & Foster 1974.…”