Transgender Children: Conundrums and Controversies--A Introduction to the Section.

This paper introduces the readership of The Psychoanalytic Study of the Child to the topic of transgender children, which will be investigated in the papers that follow. A flashpoint in the recent discourse that escorts children who self-describe as gender nonconforming is whether or not to support the practice of the medical suspension of puberty of these children by the administration of hormonal treatment. Relevant up-to-date research findings on this subject will be reviewed here. Despite those advocates and opponents who swarm around both poles, any reliable conclusions as to the long-term safety and psychological effects of puberty suppressants will remain provisional untilfuture studies proffer more definitive answers. While we await further study, the journal sees the necessity to press for dialogue concerning this conundrum. Anchoring this section is a clinical paper by Diane Ehrensaft, Ph.D., which documents the psychotherapeutic treatment of a transgender child who was prescribed puberty suppressants. The commentaries that follow and that are briefly summarized in this introduction will accent the psychoanalytic developmental point of view. This will provide the principal framework for the study of this controversy, which underscores the complementary dimensions of linear and nonlinear progressive hierarchical growth. In this context, features such as the developmentally normative fluidity of self-structures, including gender role identity, and the evolution of concrete thinking toward metaphoricity and figurative meaning-making in middle childhood and adolescence will be examined and applied to the clinical data. In addition, the argument that the use of puberty suppressants exacts a premature foreclosure on the reorganizing potential of developmental growth, and the proposed efftcts of the crosscurrents of the sociocultural body politic on these children and on the decision to opt for the suspension of pubertal growth will be explored.

Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones.

A key question concerns the extent to which sexual differentiation of human behavior is influenced by sex hormones present during sensitive periods of development (organizational effects), as occurs in other mammalian species. The most important sensitive period has been considered to be prenatal, but there is increasing attention to puberty as another organizational period, with the possibility of decreasing sensitivity to sex hormones across the pubertal transition. In this paper, we review evidence that sex hormones present during the prenatal and pubertal periods produce permanent changes to behavior. There is good evidence that exposure to high levels of androgens during prenatal development results in masculinization of activity and occupational interests, sexual orientation, and some spatial abilities; prenatal androgens have a smaller effect on gender identity, and there is insufficient information about androgen effects on sex-linked behavior problems. There is little good evidence regarding long-lasting behavioral effects of pubertal hormones, but there is some suggestion that they influence gender identity and perhaps some sex-linked forms of psychopathology, and there are many opportunities to study this issue.

Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings.

There is now good evidence that human sex-typed behavior is influenced by sex hormones that are present during prenatal development, confirming studies in other mammalian species. Most of the evidence comes from clinical populations, in which prenatal hormone exposure is atypical for a person's sex, but there is increasing evidence from the normal population for the importance of prenatal hormones. In this paper, we briefly review the evidence, focusing attention on the methods used to study behavioral effects of prenatal hormones. We discuss the promises and pitfalls of various types of studies, including those using clinical populations (concentrating on those most commonly studied, congenital adrenal hyperplasia, androgen insensitivity syndrome, ablatio penis, and cloacal exstrophy), direct measures of hormones in the general population (assayed through umbilical cord blood, amniotic fluid, and maternal serum during pregnancy), and indirect measures of hormones in the general population (inferred from intrauterine position and biomarkers such as otoacoustic emissions, finger length ratios, and dermatoglyphic asymmetries). We conclude with suggestions for interpreting and conducting studies of the behavioral effects of prenatal hormones.

Prenatal exposure to anticonvulsants and psychosexual development.

Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in humans were investigated. A follow-up study was carried out in phenobarbital- and phenytoin-exposed subjects and control subjects matched for age, sex, and the mothers' ages. Subjects were born in the Academic Medical Center between 1957 and 1972. Out of 243 exposed and 222 control subjects who were asked to volunteer, 147 exposed subjects (72 male, 75 female) and equal numbers of their matched control subjects participated in the follow-up study. They were interviewed and were asked to fill out questionnaires on gender role behavior, gender development, and sexual orientation. As a group, exposed and control subjects did not differ with respect to gender role behavior, although higher numbers of prenatally anticonvulsant-exposed subjects reported current or past cross-gender behavior and/or gender dysphoria. Three prenatally anticonvulsant-exposed subjects were transsexuals and had undergone sex reassignment surgery, a remarkably high rate given the rarity of transsexualism. In addition, two exposed males had exclusively homosexual experiences, whereas none of the control males reported exclusive homosexual behavior. The groups did not differ in attainment of pubertal psychosexual milestones.

The effects of diethylstilbestrol (DES) before birth on the development of masculine behavior in juvenile female rhesus monkeys.

Eight pregnant rhesus monkeys were injected with 100 microg diethylstilbestrol dipropionate (DESDP) from the 40th day of gestation until term, a long-term treatment. Male (n = 3) and female (n = 5) offspring were obtained. Five other pregnant females were injected with DESDP beginning on the 115th day of gestation and continuing until either the 140th day or term--a relatively short-term treatment. Five female infants were obtained from these short-term treatments. Monkeys from the treated pregnancies were assigned randomly to mother-infant social groups containing untreated male and female infants the same age. They were observed in their peer groups each weekday from 3 to 12 months of age, and the display of mounting and play behavior was recorded for each subject. Results showed that DESDP significantly increased the frequency of display of these juvenile behaviors only in long-term-treated females. However, one of the aspects of mounting that is characteristic of males (the ratio of complete to abortive mounts) was unaffected even by the long-term treatment. Thus, DESDP-treated females displayed a limited behavioral masculinization. Whether this limitation was due to dosage and/or timing or to a selective action of DESDP was not determined. DESDP-treated males were not altered in any measurable way compared to untreated males.

Early administration of 17beta-estradiol partially masculinizes song control regions and alpha2-adrenergic receptor distribution in European starlings (Sturnus vulgaris).

The vocal control system in many songbird species is a sexually dimorphic neural circuit that mediates learning and production of song. The mechanism by which this system is sexually differentiated has been investigated in only one species, the zebra finch (Taeniopygia guttata). Estradiol may be involved in the sexual differentiation of this system, as female zebra finches treated with estradiol as nestlings develop a male-like song system; however, blocking estradiol action in embryonic and nestling male zebra finches does not demasculinize the song system. Therefore, the role of estradiol in song system development is unclear. The role of estradiol in song system sexual differentiation was assessed in European starlings (Sturnus vulgaris). This species is of potential interest because it is less extreme in the degree of sexual dimorphism of the song system and song behavior than zebra finches. While in the field, starling nestlings were implanted with 500 microg of estradiol at 3 days of age. These birds were brought into the laboratory at Day 11 and hand-reared. In females, estradiol produces significant increases in the volumes of song control regions defined by Nissl stain, as well as by autoradiography for alpha2-adrenergic receptors; however, these estradiol-treated females have song systems that more closely resemble those of control females than control males. Estradiol-treated males exhibit significant hypermasculinization at 210 days of age, but this effect is transient and hypermasculinization is no longer evident at Day 345. The role of estradiol in sexual differentiation of the neural circuit mediating song behavior remains enigmatic.

Appropriate end points for the characterization of behavioral changes in developmental toxicology.

The present paper is devoted to second- and higher-tier test methods for the characterization of behavioral changes produced in rodents by exposure to noxious agents during development. The paper analyzes a series of end points that are informative about specific processes and underlying regulatory mechanisms but require greater technical sophistication and larger investments than first-tier end points. This applies to ultrasonic emissions in successive postnatal periods; to mother-pup interactions, including appropriate cross-fostering controls; to social (including sexual) interaction tests from the infantile to the young adult stage; and to a variety of conditioning and learning tests using both positive and negative reinforcement.

Pubertal arrest associated with valproic acid therapy.

Valproic acid has previously been demonstrated to decrease the secretion of multiple pituitary hormones; however, clinical symptoms associated with decreased hormone secretion have not been described. A girl is reported with complex partial seizures who was treated with valproic acid from age 10 years, 7 months to 12 years, 1 month and during this time had an arrest of both growth and secondary sexual development. Two months after discontinuing valproic acid she had resumption of both pubertal growth and maturation. A prospective controlled study is needed to determine more precisely the effects of valproic acid on growth and development.

Gender-related behavior development in females exposed to diethylstilbestrol (DES) in utero: an attempted replication.

This report concerns the role of prenatal hormones in normal and abnormal psychosexual differentiation. Several studies indicate that perinatal treatment of infrahuman female mammals with diethylstilbestrol (DES) masculinizes certain features of their brain and behavior. Accordingly, the authors have hypothesized that prenatal exposure to DES may also masculinize the gender-role behavior of girls and women. A previous study suggested that prenatally DES-exposed women show decreased interest in parenting. The authors failed to replicate these findings in a different sample despite the use of similar methodology. Post-hoc analysis shows that the assessment devices would have detected masculinization if it were present. The implications of these findings for an understanding of psychosexual development are discussed.

Health, growth and sexual development of teenagers exposed in utero to medroxyprogesterone acetate.

General health, growth and sexual development were evaluated in 74 teenage boys and 98 girls who had been exposed to medroxyprogesterone acetate (MPA) in utero, and 385 boys and 448 girls not exposed. In this 17-year prospective study, the ascertainment of the end points was 'double blind' in that neither the interviewer nor the subject was aware of our interest in MPA. On average, girls exposed to MPA reported reaching the menarche 4 months earlier than the comparison group. This difference disappeared, however, in a multiple regression analysis taking into account social class, the mother's age at menarche and height of the girl's mother and father. Boys exposed to MPA reported their growth spurt to have occurred an average of 6 months earlier and voices to have broken 5 months earlier than unexposed boys. Again, the differences between them and the comparison group disappeared after controlling for confounding variables. There were no significant differences between the MPA-exposed and comparison groups in a wide variety of indices of health reported by the teenagers' mothers. These findings are consistent with the hypothesis that intrauterine exposure to MPA, in the doses used for pregnancy maintenance or for contraception, poses no threat to the long-term health and development of the progeny.

Sexuality in children and adolescents with cancer: pediatric oncology nurses' attitudes and behaviors.

It is essential that health professionals openly discuss how cancer may affect the developing sexuality of childhood cancer patients. This study was conducted to explore nurses' attitudes and behaviors regarding sexuality in cancer patients. Results are reported for a subset of a larger study (N = 937) from subjects who indicated that their practice included children and/or adolescents (N = 156). The Williams-Wilson Sexuality Survey was used to measure attitudes towards sexuality in cancer patients, behavior in nursing care related to the sexuality of a cancer patient, and attitudes towards sexuality in the child and/or adolescent with cancer. The majority of subjects agreed that sexuality should be a routine component of nursing care, yet less than half had actually discussed an alternation in sexuality with an adolescent patient. More than one third said they were not comfortable in initiating such discussions. However, they were comfortable in discussing sexuality concerns when these discussions were initiated by the patient and/or family.

Prenatal sex hormones and the developing brain: effects on psychosexual differentiation and cognitive function.

PIP: This paper hypothesizes that sex hormones may have an influence on human brain differentiation and thus play a role in psychosexual differentiation. Such effects, if any, would be clinically relevant to the management of patients with a problem of intersexuality and for the evaluation of pregnancy drugs. A review of studies on patients with endocrine syndromes, including those with an excess or lack of androgen during fetal development strongly suggest that prenatal hormones exert a limited effect on sex-dimorphic behaviors such as physical energy expenditure, childhood rehearsal of parenting, and other related behaviors. The effects of hormone administration during pregnancy are not well known because relevant research studies are rare and often have methodological problems due to the necessary long-term follow-up studies and its attendant logistical problems. Available information therefore is fragmentary. With progestogens, extensive animal research has shown both androgenic and antiandrogenic effects of various progestogens on genital differentiation, gonadotropin regulation, and sex-dimorphic behavior. In humans, administration of certain C-19-derived progestogens has resulted in genital masculinization of a significant minority of female newborns. However, studies have also shown that while these exposed girls exhibited long-term tomboyism, their gender identity was feminine. There was also no evidence that such females, after puberty, developed a homosexual orientation. Boys exposed to medroxyprogesterone acetate in 1 study did not differ significantly from normal controls with respect to a variety of sex-dimorphic behaviors. On the other hand, exogenous estrogens, both steroidal and nonsteroidal, have been shown to exert paradoxical effects on genital morphology and behavior in subhuman animals, i.e., masculinize females and demasculinize males. In humans however, no investigations have yet been reported on behavior effects of prenatal estrogen treatment alone in man, and studies on estrogen-progestogen combination in human subjects have yielded inconclusive results regarding sex-dimorphic behavior.^ieng