Psychological Aspects of the Treatment of Patients With Disorders of Sex Development

David E. Sandberg, Ph.D.; Melissa Gardner, M.A.; Peggy T. Cohen-Kettenis, Ph.D.


Semin Reprod Med. 2012;30(5):443-452. 

In This Article

The Neonatal Period and Infancy

The presence at birth of a congenital anomaly affecting a child's genital appearance or future reproductive function can engender a "psychosocial emergency" for parents and healthcare providers. Atypical genital anatomy may represent, for both the clinician and family, the most challenging aspect of otherwise complex and even life-threatening conditions (most notably classic CAH). It is in this context, shortly following birth, that major (some irreversible) decisions are made, including gender assignment and urogenital surgery.

Family-centered strategies for clinical care are particularly important as family attitude and function are widely acknowledged to affect medical and surgical decisions as well as the psychosocial development of children diagnosed with a variety of medical conditions.[22] To optimally counsel parents, mental health providers need to take into account parents' capacity to manage uncertainty regarding psychosocial and psychosexual outcomes as the child develops. Family and cultural factors[3,23] will also likely play an important role in the perceptions of the child's condition and interpretation of complex medical and genetic information. The challenge for mental health providers is to educate parents in a balanced manner about the genetic and biologic origins of the DSD and its implications for their child's physical health and HRQoL that positions them to make informed decisions regarding elective interventions, for example, genital surgery.

Psychological Aspects of Gender Assignment

Parents may experience shock if the biological sex of their newborn is not immediately apparent. This is, in part, related to parents experiencing difficulty in coping with uncertainties of the child's development. The consensus recommendation not to use gendered pronouns ("he" or "she") as long as the gender assignment has not yet been decided, adds to this uncertainty. However, referring to the child in a way that has to be changed after the diagnosis has been made is considered even less desirable.

The 2006 DSD consensus statement,[3] states that all newborns should receive a gender assignment with the decision being informed by expert evaluation delivered by an interdisciplinary team working closely with the parents. Gender assignment decisions are typically guided by a combination of diagnosis and long-term, adult follow-up studies that focus on gender identity stability and other psychosexual outcomes (e.g.,).[24–27] "Gender identity" refers to a person's inner sense of being a boy/man or girl/woman.[28] Unfortunately, for some DSD, adult gender identity cannot confidently be predicted.[29–32] This is because there is still little known about the relative contribution of biological (e.g., genes, prenatal sex hormone exposure) and non-biological influences (e.g., parental attitude, peer influences, cultural context) on gender identity development and stability. Critical stages in the development or potential interactions of the various factors are also unclear.

Psychosexual outcomes in DSD have been most extensively studied in 46, XX CAH.[33] These studies show that the vast majority of those raised as girls develop and maintain a gender identity as girls/women across the lifespan. However, a less strong female identification, some gender discomfort, and even gender dysphoria occur more often in this group than in women without CAH. Reviewing studies on psychosexual outcome in DSD up to 2007, de Vries and colleagues reported that 10 of 217 (5%) of female-reared adolescent and adult women with CAH experienced some form of gender dysphoria and made a complete social gender transition (i.e., lived completely and permanently in the male role).[32] Masculine gender-role behavior among adult women was fairly common. Similarly, prepubertal girls with CAH exhibited more masculine and less feminine interests, behaviors and preferences than girls without CAH. Gender-atypical behavior is more pronounced among CAH girls and women with the salt-wasting form of CAH than those categorized as simple virilizers.[34–36]

DSD that are a consequence of errors of androgen biosynthesis have historically been particularly challenging from the standpoint of gender assignment. Long-term outcome studies of persons with 46, XY 5-α-reductase type 2 deficiency (5α-RD-2) and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD-3), suggest that large proportions of those reared as girls, subsequently identify as men if they are allowed to experience a spontaneous masculinizing puberty. Following the first observations of gender change among 5α-RD-2 individuals reared as girls in the Dominican Republic,[37] gender change was reported in 17β-HSD-3 and in other societies.[26] Gender change, however, does not always occur, even in societies that highly value the male role. In the review by de Vries et al.,[32] 69 of 117 5α-RD-2 (59%), and 20 of 51 17β-HSD-3 (39%) persons reared as girls, and all older than 12 years, experienced gender dysphoria to the extent that they decided to live as boys/men. In one study by Richter-Appelt et al,[38] five persons with 5α-RD-2 and 17β-HSD-3 reared as girls, scored significantly lower on a "female gender identity scale" than a female comparison group and one of the five also had a significantly higher male gender identity score than the female comparison group on a "male gender identity scale."

In contrast to the common pattern of gender change from female to male in persons with 46, XY DSD secondary to errors in androgen biosynthesis, a recent report suggests a markedly different outcome. In addition to demonstrating marked variability in genital phenotype associated with alterations in the 5α-reductase type 2 gene (SRD5A2) responsible for 5α-RD-2, Maimoun and colleagues[39] reported that only 5 of 40 patients assigned female (12.5%) subsequently changed their gender to male. This proportion is remarkably lower than the 59% reported by de Vries et al.[32] Unfortunately, gaps in details provided, in particular the age of patients at the time of recording gender assignment, make it difficult to reconcile these highly discrepant observations. Whether the proportion of those affected with 5α-RD-2 that ultimately change identity from female to male is relatively large or small, information on parental rearing styles, psychosexual development, or more subtle signs of gender discomfort are essential for an understanding of the variability in gender identity outcome. Unfortunately, virtually no reports provide such information.

Persons with complete androgen insensitivity syndrome (CAIS) reared as girls, with limited exceptions,[40] develop and maintain a female gender identity throughout their lives.[25] However, there may be more variability in their gender behavior than commonly assumed: women with CAIS recruited through the United Kingdom Database of Ambiguous Genitalia and Intersex Disorders recalled more male-typical childhood toy and activity preferences than women recruited through an AIS support group. In contrast, the same registry-recruited group was more strongly heterosexual in the previous 12-month period than the AIS support group.[41] In a second study possibly signaling greater gender-atypical gender development in CAIS women than previously reported, two of five women with CAIS scored low in terms of a female gender identity.[38] Despite these greater than expected masculine interests and behavior, not one of 98 women with CAIS in the de Vries et al. review[32] reported gender dysphoria or made a social gender transition.

Gender identity shows considerably greater fluidity among persons born with partial androgen insensitivity syndrome (PAIS). In 46 female-reared adolescents and adults, 5 (11%) were gender dysphoric or started to live in the male role later in life. This percentage was even higher in the male-reared group; 5 of 35 (14%) was gender dysphoric or made a social gender transition. All gender changes took place in adulthood. In Richter-Appelt et al's study,[31] one of three PAIS individuals reared female scored significantly lower than female controls on the "female gender identity scale."

From these studies and studies on other conditions such as penile agenesis, penile ablation, cloacal exstrophy of the bladder and micropenis,[25,27] it appears that testosterone influences the development of a male gender role and probably increases the chance of a male gender identity development. However, even in circumstances in which the person has been prenatally exposed to high levels of testosterone and reared as girls from birth, a female adult gender identity is the rule rather than the exception.[24]

Gender assignment does not pose insurmountable problems in most DSD. However, in some conditions (e.g., PAIS, 17β-HSD-3, or 5α-RD-2), the choice may be a difficult one because so little is known about postnatal events in the social environment that potentially intervene between early biological events to modulate gender identity outcomes (Fig. 1). For instance, should a child with 5α-RD-2 who has a complete absence of virilized external genitals be gonadectomized early to prevent a masculinizing puberty and reared as a girl? This choice would be associated with lost capacity for a spontaneous puberty, potential fertility[42] and need for lifelong androgen replacement therapy. Alternatively, if gender assigned and reared as a boy, what would be the person's experience living with very atypical external genitals? In the decision, non-medical factors such as healthy psychological development and the potential for a good quality of life as boy/man or girl/woman, the ability of parents to cope with uncertainties, and medical factors such as surgical possibilities, potential for fertility, and need for hormone replacement need to be included. Even considering all these factors, one cannot always be completely certain that the chosen gender assignment will result in a good quality of life. Unfortunately, the evidence on quality of life outcome of adults with DSD that could be used to inform such decisions is currently scarce (e.g.,).[43]

Gender Development

Under normal circumstances, few give much thought to their gender development, as somatic sex, gender identity, and gender role typically develop in accordance with each other. A newborn does not immediately have self-awareness of his or her sex and gender. Such self-awareness evolves gradually during infancy and childhood. In the absence of discordance between aspects of sex and gender, few will reflect on their gender identity or gender role.

Developmental psychology theories have attempted to account for the process of gender development, emphasizing the influences of cognitive and affective learning in interaction with parents, peers, and other aspects of the social environment.[28] Gender role refers to the pattern of masculine or feminine behavior and interests of the person that is conditioned by culture and upbringing. Long before children make consistent and systematic use of genital information as a criterion for sex classification, they have knowledge about gender stereotypes and display gender-role behavior characterized as either feminine or masculine. Adults and peers influence gender development directly by reinforcing or discouraging gender-role behaviors and indirectly by serving as role models.

Biology, however, also plays a role in the shaping of gender-role behavior. There is substantial evidence from animal and human research that sex hormones, androgens in particular, play an important role in the differentiation of gender-role behavior, gender-typed preferences, and even aspects of personality. Studies of sex-steroid levels in the blood or amniotic fluid of pregnant women and gender-related behaviors of their children have demonstrated positive associations between androgen exposure and male-typical behavior in healthy girls.[44–47] Timing, dose and type of androgen exposure seem to be important.[48] Similarly, studies of gender-role behavior in persons with DSD also suggest that sex hormone exposure during sensitive development periods play a role in the formation of behaviors exhibiting sex-related variability.[35,36,49] The influence of early sex hormone exposure on the formation of gender identity is less clear.

Genital Surgery

Questions about surgery to "normalize" genital appearance and function can arise shortly after birth. Surgeons have the responsibility to describe to families surgical options and the range of possible consequences from infancy to adulthood.[3] Although there appears to be consensus on some types of genital surgery (e.g., neonatal surgery in case of severe virilization in female-assigned children or gonadectomy in female-reared children with PAIS and CAIS[3]), decisions remain that are not obvious. Controversies regarding types of surgery and their timing remain unresolved. This is readily apparent in conditions commonly diagnosed late, such as Mayer-Rokitansky-Küster-Hauser syndrome[50] or CAIS,[51] in which older girls/women need to decide whether they will opt for vaginal surgery or dilation to create a vagina and when it is optimal to proceed based on psychological readiness. If there is not enough evidence from outcome studies that unequivocally demonstrate superiority of one approach over another, then choices depend on individual characteristics and detailed discussions with the patient (and, as applicable, the parents) regarding perceptions of advantages and disadvantages of the various choices. The goals of genital surgery and, in particular their consequences for sexual function and satisfaction need to be explicitly addressed. Naturally, the clinician who provides this counseling should feel comfortable when speaking about sexuality. Systematic decision-making aids, as developed for some conditions (see The Foundation for Informed Medical Decision Making),[52] would be very valuable, but have yet to be developed for DSD.

Information Management

Information management refers to two processes: first, the sharing of information about the DSD between clinicians, the parents and the child and second, the sharing of information about the condition by the child or family with the wider social environment. Both processes are activated to varying degrees once families are aware that their child has a DSD; this may begin with a prenatal diagnosis.

The first process often requires more than just presenting information in a clear manner. Some of the information potentially carries strong emotional implications. This is commonly the case with information about karyotype and gonadal status, especially when these results are discordant with the gender of assignment. To learn that the condition implies infertility may also pose challenges for coping. The second process, involving education of those beyond the affected person and parents, requires careful balancing of the potential advantages and disadvantages. It is still an open question whether sharing information about the DSD with the wider social environment will have positive or negative consequences for the child. Living a "normal" life with a secret could be harmful, just as living a life without secrets but with an increased risk of stigmatization or rejection. The advice currently given to parents remains largely based on clinicians' personal opinions on what would be preferable, considering their evaluation of the family, the child, and their wider social and cultural context. Research on the effects of timing, type of information (and a potential interaction of the two), the way of conveying information, and the influence of cultural, family and child factors on how the information is managed is virtually nonexistent. Nevertheless, clinicians can find guidance in the general pediatric literature concerning physician-parent communication, especially as it relates to the sharing of "bad news."[53]

Initial statements to parents should provide support and information. With regard to gender, healthcare providers should counsel families on differences between "gender identity," "gender-role," and "sexual orientation," including general, evidence-based statements on the psychosexual development of individuals born with the child's particular condition. The process (and not a single event) of educating the parents and the affected person requires a flexible individualized approach. Medical education and counseling for children and their families is a continuing process of gradually increasing complexity that takes into account health literacy[54] and emotional readiness. Fostering open communication between the parents and child is a high priority.[55–57] This iterative process should be planned with the parents from the time of diagnosis.[58]