The Dilemma of Sex Reassignment in an Adolescent with 17β-HSD-3 Deficiency Raised as a Female: Ten-Year Follow-Up

Abstract

A number of patients with defective differentiation of the genital system, described in the literature by various terminologies (Dacou-Voutetakis, 2007; Hughes et al., 2006), wish to have sex reassignment in adolescence or adulthood. One of the disorders prompting the request for sex reassignment after childhood is the deficiency of 17b-hydroxysteroid dehydrogenase-3 (17b-HSD-3) caused by mutations in the HSD17B3 gene. The enzyme 17b-HSD-3 is involved in the terminal phase of testicular steroidogenesis and specifically catalyzes the conversion of androstenedione (A) to testosterone (T). Persons with this defect have near-normal or ambiguous female external genitalia at birth due to the absence of testosterone and dihydrotestosterone when the external genitalia differentiate (Gooren, 2002). Individuals with 17b-HSD-3 deficiency are considered as females and are raised as girls. At puberty, however, they become virilized as a result of an increase in T and dihydrotestosterone levels due to the action of 17b-HSD-isoenzymes and peripheral conversion of A to T (Sobel & Imperato-McGinley, 2004). In a recent review dealing with these patients, the opinion expressed was that genital appearance at birth does not determine psychosexual outcome and that the general appearance of the child in combination with masculine behavior are stronger determinants for the development of male gender identity (Cohen-Kettenis, 2005). In the present report, we describe an XY individual with 17b-HSD-3 deficiency raised as female, the dilemmas arising at age 17 years when the question of sex reassignment was seriously considered, as well as her follow-up of 10 years post-feminizing surgery of the external genitalia. The patient, currently 27-years-old, is the fourth oldest of five children of a family living in a rural area of a small Greek island. The family does not belong to any specific religious group. At birth, no abnormality of the external genitalia was identified. Shortly thereafter, however, the mother questioned the appearance of the external genitalia but refused testing in Athens as recommended by the local pediatrician. The patient attended primary school up to the 6th grade but was unable to learn reading, writing, and arithmetic, similar to her mother and one brother and in contrast to two other children of the family. A school for children with special needs was not available in the area at that time. Quite early, the patient started to work at the family farm located some distance away from home, caring for sheep and other animals and thus living a rather isolated life. At the age of 8 years, the patient was brought by her father to our hospital but after a few consultations they left, stating that they would come back later ‘‘after finishing with jobs on the farm.’’ At that time, the patient had the appearance of a normal girl and presented only mild clitoral enlargement without hypertrichosis. With the girl’s onset of puberty, however, the pediatrician noted evidence of virilization. One member of our team (CDV), accompanied by the local pediatrician, visited the M. Liakopoulou (&) Child Psychiatry Department, ‘‘Aghia Sophia’’ Children’s Hospital, Athens University School of Medicine, Athens 11527, Greece e-mail: mliakopo@otenet.gr