Gender Change in 46,XY Persons with 5α-Reductase-2 Deficiency and 17β-Hydroxysteroid Dehydrogenase-3 Deficiency

Abstract

Individuals with 5alpha-reductase-2 deficiency (5alpha-RD-2) and 17beta-hydroxysteroid dehydrogenase-3 deficiency (17beta-HSD-3) are often raised as girls. Over the past number of years, this policy has been challenged because many individuals with these conditions develop a male gender identity and make a gender role change after puberty. The findings also raised doubts regarding the hypothesis that children are psychosexually neutral at birth and emphasized the potential role of prenatal brain exposure to androgens in gender development. If prenatal exposure to androgens is a major contributor to gender identity development, one would expect that all, or nearly all, affected individuals, even when raised as girls, would develop a male gender identity and make a gender role switch later in life. However, an estimation of the prevalence of gender role changes, based on the current literature, shows that gender role changes occur frequently, but not invariably. Gender role changes were reported in 56-63% of cases with 5alpha-RD-2 and 39-64% of cases with 17beta-HSD-3 who were raised as girls. The changes were usually made in adolescence and early adulthood. In these two syndromes, the degree of external genital masculinization at birth does not seem to be related to gender role changes in a systematic way.

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

“…This story illustrates the enormous programming influence of the intrauterine period on gender. Other cases have been described in the literature (32), due to enzymatic disorders (33)(34)(35) or to cloacal exstrophy (36), that support the existence of early permanent programming of brain sex by biological factors and androgen exposure, rather than by social environment and learning (17,37).…”

“…However, when testosterone production increases in these XY children during puberty, this "clitoris" grows to penis size, the testicles descend, and the child's build begins to masculinize and become muscular. Despite the fact that these children are initially raised as girls, the majority (60%) change into heterosexual males (24,34,35,42,43), apparently due to the organizing effect of testosterone on early brain development. Boys who are born with a cloacal exstrophy -i.e.…”

“…-5α-reductase-2 or 17β-hydroxy-steroid-dehydrogenase-3 deficiency (34,42,43 erotically attracted to women), who were not treated hormonally, showed that a number of brain areas in the transsexual hypothalamus were activated by pheromones in a sex-atypical way. Although the functional reactions in the hypothalamus to an estrogen-derived pheromone were predominantly female, MtF transsexual people also showed some characteristics of a male activation pattern (97).…”

46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5α-Reductase-2 Deficiency, or 17β-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes

“…The clinical presentation of 17 β -HSD-3 deficiency can be confused with CAIS as affected individuals often present with female external genitalia prior to puberty [50, 51]. If the testes remain in situ, virilization at puberty occurs in a manner that is similar to what is observed in 5 α -RD-2 deficiency [50, 52]. …”

Sexual difference, identification and object choice in individuals with sex differentiation disorders

“…However, some virilization takes place during the puberty of these individuals through the conversion of T into DHT by enzyme type 1. Consequently, individuals raised as girls often undergo a postpubertal female-to-male change in "gender identity and role" (Blizzard, 2002;Bradley, 1998;Cohen-Kettennis, 2005).…”