This 13 year old boy presented for an outpatient evaluation requesting puberty blocking medication and hormone therapy so he could become a girl. He reported feeling like a girl for as long as he can remember; he has worn predominantly female clothing for the past five years. Although he's uncomfortable doing so, he dresses "like a boy" in school only because of fears of verbal and physical harassment. He also reported feeling "trapped" in the body of a boy. He denied any physical complaints and the review of systems was non-contributory.
His medical history is significant for reported physical abuse warranting placement outside of his home. He underwent psychiatric hospitalization one year earlier for suicidal ideation related to anger associated with gender issues. He has been diagnosed as having attention deficit disorder. He has been seeing a psychologist weekly for approximately one year, specifically for issues related to gender identity.
He has had not contact with his biological family for many years; their parental rights have been terminated. He is in eighth grade and is an average student. He denied alcohol or street drug use. However, he has tried using intramuscular injections of estrogen, which he obtained on the street. He is sexually active with male partners only and considers himself a heterosexual female. He uses condoms 50% of the time for anal sex. He had one HIV test which was negative approximately one year ago. He reported having few friends because "no one is like him."
On physical examination, he was dressed in female clothing, including long hair and fake breasts of water balloons. His growth parameters and vital signs were normal. His general exam was unremarkable. He was Tanner stage IV with an uncircumcised penis.
Robert Listernick, MD, general academic pediatrician: Let me start out with a question that I ask in all seriousness, how shall we address this person for the rest of the conference? What is the proper pronoun to use?
Robert Garofalo, MD, adolescent medicine specialist: The use of the appropriate pronoun is a tremendous issue for these youth. My approach has been to use the pronoun for the gender that they prefer; in this case, I would use "she."
Dr. Listernick: Does anybody have an objection to that?
Joel Frader, MD, pediatric ethicist: How we refer to the patient within this conference is not as important as what we say to the person directly. Since one of our most important functions is to make the patient feel comfortable within the medical environment, we should use the pronoun which makes the patient feel most comfortable.
Robert Tanz, MD, general academic pediatrician: I don't disagree with anything that has been said. However, this is still biologically a male. Referring to this person as anything other than a male in the medical record is misleading and may potentially lead to medical error.
Dr. Listernick: For the sake of clarity during this conference, let's refer to the patient as "he". What term should we use to describe his problem?
Dr. Garofalo: I would refer to this individual as "transgendered", meaning someone whose gender identity is discordant with their biological or genetically determined anatomical sex. From a clinical perspective, one might call it gender dysphoria or a gender identity disorder. According to the Diagnostic and Statistical Manual of Mental Disorders-IV, there are several criteria one must have in order to establish this diagnosis. In children, the disturbance is manifested by at least four of these conditions: 1) repeatedly stating a desire to be, or insistence that he or she is, the other sex; 2) preference for cross-dressing or using attire of the opposite of one's biologic sex; 3) strong and persistent preferences for cross-sex roles in make-believe play or persistent fantasies of being the other sex; 4) an intense desire to participate in the stereotypical games and pastimes of the other sex; and 5) a strong preference for playmates of the other sex. In adolescents and adults, the disturbance is manifested by symptoms such as a stated desire to be the other sex, frequent passing as the other sex, desire to live or be treated as the other sex, or the conviction that he or she has the typical feelings and reactions of the other sex. In addition, the patient should have a persistent discomfort with his or her sex or a sense of inappropriateness in the gender role of that sex. In children, a boy may state that his penis or testes are disgusting and assert that it would be better not to have a penis. He might have an aversion toward stereotypical male toys, games, and activities. Girls might reject urinating in a sitting position. Adolescents might have a preoccupation with getting rid of primary and secondary sex characteristics or a belief that he or she was born the wrong sex. This disturbance should cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Keep in mind that, although this classification may be useful in a clinical setting, many transgendered individuals do not think of themselves as "pathologic", making the term gender identity disorder at times offensive.
Dr. Listernick: How does this relate to someone considering himself or herself homosexual?
Jill Benchell-Weissberg, PhD, child psychologist: Homosexuals identify themselves as the gender that they were born. They are interested in individuals of the same gender as sex and life partners. Individuals with a gender identity disorder truly believe that they are different from their phenotypic gender.
Dr. Garofalo: I believe that it's a little more complicated than that. Although the research is far from conclusive, there appears to be a significant percentage of individuals with this condition who adopt homosexual or bisexual identities as adults. While we have come a long way in our understanding of the spectrum of sexual orientation from homosexual to heterosexual, most people still think of gender identity as a binary issue. However, many of these individuals exist along a spectrum of gender from male to female, including many identities between the two. These individuals face extreme degrees of marginalization and stigmatization from virtually all aspects of society. Children and adults who are homosexual may be able to hide their sexual orientation from their peers; this may serve a protective function in terms of societal stigma. Those with gender dysphoria have difficulty doing so, feeling trapped inside the body of the wrong gender. This may lead to acting out in socially inappropriate ways.
Dr. Listernick: How do his psychological problems relate to his gender identity disorder?
Dr. Benchell- Weissberg: Teasing out these issues can be extremely difficult. I would try to sort out which of his many problems came first and which are comorbidities of his gender dysphoria. When one feels completely socially isolated, it's not hard to understand how emotional difficulties can follow rapidly.
Earl Cheng, MD, pediatric urologist: We're making some assumptions about this person before he's had a complete medical evaluation. From a medical standpoint, we need to first assure ourselves that he's a genotypic male and that there is not an underlying intersex disorder.
Dr. Listernick: What should be our initial medical evaluation?
Don Zimmerman, MD, pediatric endocrinologist: First, we should perform a karyotype to make sure that this individual is genotypically a male. Genotypic girls who have the non-salt losing form of 21 -hydroxylase deficiency, the most common type of congenital adrenal hyperplasia, may present late in childhood with signs of virilization. I have seen 46 XX individuals who were raised as males; enlarged inguinal lymph nodes in these individuals were misidentified as "undescended testes". We have reason to believe that in utero exposure to high levels of testosterone may have profound effects on brain development and sexual identity. There are numerous studies of girls with 2 !-hydroxylase deficiency who were diagnosed and treated appropriately in the neonatal period, who preferred traditionally "male" activities and behaviors in childhood and who ultimately adopted a "male" lifestyle as adults. Obviously, this is not relevant in this particular case. In this individual, at a minimum, we should measure the sex hormones, testosterone and estradiol, as well as the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH).
Dr. Listernick: Are there examples of individuals who are exposed to abnormal levels of estrogen in utero?
Dr. Zimmerman: Everyone is exposed to enormous levels of estrogens in the womb. The presumed hormonal effect on the biopsychology of an individual is secondary to the amount of androgens to which one is exposed in utero.
Dr. Cheng: We really know very little about the biology and psychopharmacology of gender dysphoria and intersex. I use the term "intersex" to describe a group of individuals who, whether through phenotypic, genetic, pharmacologic, or psychological factors, present with ambiguity regarding their gender identity. It's incumbent on health care professionals to study the medical aspects of these individuals carefully before we state that their condition is "psychological". With that said, despite what we may have thought in the past, we have found that it's not really up to us or their parents to define their gender. Virilized girls with 21 -hydroxylase deficiency may ultimately declare themselves "male" as adults, no matter how they are raised. Undervirilized XY males exposed to low levels of androgens may decide that they are "female" as adults. In some situations, individuals may not declare themselves as either exclusively male or female; other cultures have come to accept this, but Western culture has not.
Dr. Benchell-Weissberg: While it's important to look at the medical aspects of these individuals, we shouldn't forget that they may be praying every night before they go to bed that they wake up the next morning as a different sex than they outwardly appear.
Dr. Cheng: I agree, but I believe that sometimes it can help these individuals tremendously to understand that there is an actual biologic basis for their feelings. One example is the XY boy who is born with cloacal extrophy, a condition in which the bladder and the bowel are external to the peritoneal cavity at birth. These individuals have very small phalluses and testes; they often undergo surgical correction and castration as a newborn and are raised as females. The majority of these children ultimately declare themselves as "male" during adolescence. When they're finally told their underlying diagnosis, the amount of psychological relief that they experience is enormous.
Dr. Listernick: Let's move forward. This patient had a normal medical evaluation, including karyotype, sex hormones, and gonadotropins. Before we discuss the specifics of what we can offer him, how would we proceed if he were 30 years old and the psychiatric profile indicated he was an appropriate candidate for hormonal therapy?
Dr. Zimmerman: Assuming one wishes to assist a hormonallymale individual into becoming hormonally-female, two things must be accomplished - testosterone production must be suppressed and supplemental estrogen must be given. If only estrogen is given, supraphysiologic doses would be necessary in order to suppress pituitary gonadotropins, which, in turn, stimulate the testes to produce testosterone. Such high doses of estrogen would place the individual at high risk for thrombosis. This risk can be ameliorated somewhat through the use of transdermal estrogen. Most of the prothrombotic effect of estrogen is due to the high concentrations of estrogen presented to the liver from the portal circulation after oral intake. A different approach is to use longacting analogues of gonadotropinreleasing hormone which essentially shut down the hypothalamicpituitary-gonadal axis. In addition, we would give the patient small physiologic doses of estrogen.
Dr. Garofalo: It's important to understand that the Harry Benjamin Society has published fairly specific medical and mental health guidelines for die treatment of transgendered individuals. Although they're not based on rigorous evidencebased medicine or solid research, they are the principles to which many physicians presently adhere. They describe a "real life test", which is a period of time spent living in the world as the opposite gender, prior to the use of hormonal therapy or surgery. These standards of care are quite restrictive, too restrictive for some physicians to follow. In particular, the standard of care for adolescents with these issues is uncertain.
Dr. Cheng: To be clear, obviously no one would recommend reconstructive surgery for a pre-adolescent. This type of surgery is irreversible. I have little experience with adults. However, urologie surgeons are fairly decent at making males into females, but nowhere near as good doing the reverse surgery. Although we can preserve the proximal aspects of the erectile tissue, the glans, and sensation at the inner base of that area, there is little good long-term research as to how these individuals perform sexually. You should also keep in mind that many transgendered individuals don't request surgery.
Dr. Listernick: Does this child have the right to ask for these medical and surgical procedures?
Dr. Frader: Let's not talk about "rights"; I don't think that such language advances the discussion. Rather, we should focus on what might be the best course of action for this child. Is it appropriate at this time to do anything that is irreversible? I suspect that most of us, as both parents and physicians, would say "no".
Dr. Listernick: To play devil's advocate, are there any data that suggest that this child's attitude toward his body at age 13 is ever going to change?
Dr. Benchell- Weissberg: Again, it's important not to confuse sexual orientation with gender. Gender, one's sense of being male or female, solidifies around the age of 5 years. Sexual orientation solidifies during adolescence.
Dr. Garofalo: The unfortunate fact is that the data that exist imply that there's very little chance that these feelings will change. Even though some individuals at age 13 are capable of making many decisions regarding their own health care, no health care provider would allow such surgery to be performed at this age. Even in adults, one would typically wait several years after undergoing hormonal therapy before orchiectomy and reconstructive surgery would be considered. The main issue of this case is the appropriateness of letting this adolescent start hormonal therapy.
Dr. Listernick: How does the fact that he's in foster care affect these decisions?
Dr. Garofalo: In this case, I believe the decision is more difficult since he's a ward of the state; it's unlikely that the state will see any of mis controversial therapy as being in his best interest. Ironically, if he were homeless, he might be considered emancipated, making the process easier. Of course, this depends on how one views emancipation and adolescents' rights.
Dr. Benchell- Weissberg: The other aspect that we should consider is the enormous danger that these individuals face day to day just walking outside. They are likely to be teased and physically attacked. Sometimes we have to devise a plan that's just going to keep them safe walking out the door.
Dr. Garofalo: I agree wholeheartedly. Studies in urban centers estimate that 20%-40% of adult transgender individuals are infected with HIV. They can't get jobs or an education; many of them end up homeless and turn to prostitution. Prostitution is not uncommon because it serves a dual purpose of validating their chosen gender identity and providing them with an "easy" income.
Dr. Cheng: Our society does not accept sexual ambiguity, as do other more primitive societies. For example, in the best of all worlds, newborns with genital ambiguity should be left alone until the age of six or seven, when their gender identity is better defined. This is perhaps the best time for them to declare gender identity. However, every family that I've counseled has chosen to have immediate genital reconstructive surgery. What is best medically may not fit with societal expectations
Dr. Garofalo: For the record, the standard of care in centers which see a number of these individuals is such that the institution of hormonal therapy under the age of 16 would be extremely unusual. However, I am certainly aware of exceptions in individuals who had received extensive counseling at a young age.
William Brinkman, MD, pediatric chief resident: What do we tell parents of six and seven-year-old children who have behaviors that are deemed "gender-inappropriate"?
Dr. Benchell-Weissberg: As difficult as it may be, it's extremely important for parents in this situation to try to tolerate ambiguity. The statistics show that of all "gendervariant" children in this age group, 60% grow up lesbian or gay, 38% grow up heterosexual, and 2% become transsexual. Parents and professionals need to be very cautious around such children and allow them to explore and move forward at their own pace.
Dr. Listernick: Thank you, everybody.