Intersex care and priorities

The transition to adulthood constitutes a particular challenge for patients with somatic intersexuality, because there are very few medical and mental health professionals specialised in the care of adults with such conditions

In medical use, intersex refers to an individual in whom the development of the external and/or internal genitalia has been atypical, that is, different from what is typically seen in the average male or female, resulting in “genital ambiguity” that may raise the question about the appropriate assignment of gender in the traditional binary gender system. The overall incidence of intersex conditions is difficult to estimate. At the International Consensus Conference on Intersex in 2005, in which two leading intersex activists participated, a new global term “Disorders of Sex Development” (DSD) was introduced, which now included the intersex conditions (labeled “hermaphroditism” in the preceding medical nomenclature), along with other conditions, including the much more frequent sex-chromosome variants of Turner Syndrome and Klinefelter Syndrome, which usually are not associated with genital ambiguity. As many people object to being labeled as having a “disorder,” alternative read-outs of “DSD” such as “Difference(s) of Sex Development” or “Divergence(s) of Sex Development” have subsequently come into use, especially in advocacy groups. It is important to realize that “DSD” and “intersex” are not synonymous: although all intersex conditions are DSDs, not all DSD conditions are intersex. I, therefore, will continue to use the much narrower term “intersex” in the remainder of this article.

What causes confusion is that the medical term “DSD” (as well as “intersex”) is defined strictly by biological criteria, whereas Lesbian, Gay, Bisexual, Transgender and Queer or are questioning their sexual identity - LGBTQ refers primarily to identities, that is, sexual orientation identities or gender identities. Some individuals (with or without somatic intersexuality) who develop gender dysphoria and experience their identity as being at variance with their originally assigned gender do indeed use “intersex” (“between the sexes” in literal translation) as an identity label. Most individuals with a somatic intersex condition, however, identify as female or male, that is, within the gender binary. In contrast, clinicians occasionally encounter a person with gender-identity variance without somatic intersexuality who tries to persuade them that she/he does in fact have a form of somatic intersexuality or may even self-administer cross-sex hormones, without disclosing it, to prove that point (author's unpublished observations).

The term “transgender” is commonly applied to gender-identity variant individuals with a standard 46,XY or 46, XX karyotype and—before sex-reassignment surgery—the respective male-typical or female-typical reproductive tract. By contrast, somatic intersexuality (regardless of the presence or absence of gender dysphoria) comprises a large number of diverse sex-chromosome, genetic, and hormonal variants, many of which cannot yet be definitively diagnosed in genetic terms.

Three of the better known syndromes are (1) 46,XX congenital adrenal hyperplasia (CAH) with highly variable degrees of genital masculinization despite presence of ovaries and intact uterus and proximal vaginal tract; its cause is enzyme defects in the pathways of cortisol and aldosterone biosynthesis, the effects of which include excess prenatal and postnatal androgen production by the adrenal glands; (2) 46,XY androgen insensitivity with highly variable degrees of genital hypomasculinization despite normal or high-normal testicular androgen production because of reduced responsiveness of the androgen receptor; such patients usually lack a uterus and vaginal tract, because their testes produce normal amounts of anti-Müllerian hormones; (3) 46,XY 5α-reductase-2 (5α-R2) deficiency with normal masculinization of the internal genitalia but variable hypo masculinization of the external genitalia because of a genetically caused deficiency of the enzyme involved in the conversion of testosterone to dihydrotestosterone, the androgen required for masculinization of the external (but not internal) genitalia; patients with 5α-R2 deficiency undergo very strong somatic virilization during puberty, when an isoenzyme of 5α-R2 in another body compartment becomes activated.

The transition to adulthood constitutes a particular challenge for patients with somatic intersexuality, because there are very few medical and mental health professionals specialized in the care of adults with such conditions. In the absence of skillfully planned services to assist in the transition from pediatric to adult care, many adult patients are reluctant to access providers they do not know or may encounter physicians who are not experienced with their conditions, resulting in insufficient and/or inadequate medical and mental healthcare. Additional problems may arise if gender dysphoria develops which occurs in patients with somatic intersexuality at a rate higher than in the non-DSD population, varies with syndrome type, severity, and initial gender assignment, and can happen at any phase of life after infancy. Thus, optimal care for patients with intersexuality involves an integrated interdisciplinary team approach.

Most needed on the medical side is research on underlying genetics, optimal hormone treatment, and condition-specific best approaches to decisions regarding genital surgery, including techniques and timing. Identifying all genes involved in the development of intersexuality (involving both genes that encode transcription factors and regulatory genes) would permit more uniform genetic grouping of individuals with intersexuality, better targeting of medical treatment, and a more stringent description of condition-specific long-term medical and psychosocial outcomes. Further development of intersex-specific DNA microarrays or biochips is urgently needed to make such detailed genetic screening widely affordable. The findings would also contribute to clarifying the many steps involved in normative somatic sexual differentiation and the interaction of genetic factors (including epigenetic processes) therein.

The endocrine management is particularly complex in individuals with CAH, especially 46,XX females, because of the difficulty of finding a balance between glucocorticoid replacement and the associated suppression of adrenal androgens, which affect growth, weight, somatic virilization, and insulin responsiveness. Despite exemplary development of respective evidence-based guidelines by the Endocrine Society, much more empirical work is required, and an updating of the guidelines is currently in progress. Systematic research work on hormone replacement in the many 46,XY syndromes of intersexuality is much more limited, and an authoritative and comprehensive set of guidelines is yet to be developed.

Currently, the most controversial topic in intersex care is genital surgery for other than strictly medical indications (i.e., “gender confirming” or “normalizing”).

Should such surgery be performed at all, given the risks involved to appearance and to urinary and sexual function? In view of the risks, should it be delayed until the patient has reached the age of consent? Or at least until the patient has demonstrated a stable gender identity, and no other risk factors for the development of gender dysphoria—such as marked gender-atypical behavior, incongruent pubertal development, or disclosure of gender-incongruent features such as Y chromosomes in a patient raised as a girl—are present or expected? And which surgical techniques are optimal at which developmental stage for the diverse genital configurations created by the many different intersex syndromes and their variations in severity? Gender-confirming genital surgery of patients with intersexuality is very different from the procedures most commonly used in transgender patients without somatic intersexuality, and published guidelines increasingly recommend limitation of genital surgery on individuals with intersexuality to surgeons or surgical centers with a relative large number of such patients and much experience with related surgical procedures.

Endocrine and surgical treatments depend on the patient's assigned gender. Gender assignment requires a complex decision process, taking into consideration the biological factors involved in the development of the condition in a given patient and the associated prognosis for future development of reproductive, sexual, gender, and psychological features as well as the (sub)cultural sex/gender ideologies of the parents. A major unresolved question is whether it will become possible to identify, through brain imaging or other means, biomarkers of the sexual differentiation attained by the brain of a newborn or a preschool child or an adolescent that can serve as a guide to initial gender assignment or as an indication for gender reassignment. In any case, a comprehensive approach can improve gender assignment in terms of minimizing the likelihood of developing gender dysphoria in the assigned gender but there will always be some patients who will question their gender or develop gender dysphoria.

Given the paucity of intersex specialists, the overall organisation of both medical and psychosocial care for patients with intersexuality needs to be worked out—including communication through telemedicine techniques between specialists at multidisciplinary centers of expertise and clinical practitioners elsewhere, the involvement of support groups and advocacy agencies, the deliberate planning of transition from pediatric to adult care, and the provision of specialized care for elderly patients with intersexuality, along with the dissemination of the necessary training procedures, preferably all within the theoretical framework of implementation science.

While addressing the many specific details, the clinical team must never lose sight of the fact that their patients are human beings who are just facing some specific medical and psychosocial challenges and that the overall goal of professional intervention is to minimize societal stigma and to foster the development of healthy and happy adults with their self-esteem intact.

The writer is former Head, Department of Medical Sociology,

Institute of Epidemiology, Disease Control & Research (IEDCR)

E-mail: [email protected]

 

Intersex care and priorities

The transition to adulthood constitutes a particular challenge for patients with somatic intersexuality, because there are very few medical and mental health professionals specialised in the care of adults with such conditions

In medical use, intersex refers to an individual in whom the development of the external and/or internal genitalia has been atypical, that is, different from what is typically seen in the average male or female, resulting in genital ambiguity that may raise the question about the appropriate assignment of gender in the traditional binary gender system. The overall incidence of intersex conditions is difficult to estimate. At the International Consensus Conference on Intersex in 2005, in which two leading intersex activists participated, a new global term Disorders of Sex Development (DSD) was introduced, which now included the intersex conditions (labeled hermaphroditism in the preceding medical nomenclature), along with other conditions, including the much more frequent sex-chromosome variants of Turner Syndrome and Klinefelter Syndrome, which usually are not associated with genital ambiguity. As many people object to being labeled as having a disorder, alternative read-outs of DSD such as Difference(s) of Sex Development or Divergence(s) of Sex Development have subsequently come into use, especially in advocacy groups. It is important to realize that DSD and intersex are not synonymous: although all intersex conditions are DSDs, not all DSD conditions are intersex. I, therefore, will continue to use the much narrower term intersex in the remainder of this article. What causes confusion is that the medical term DSD (as well as intersex) is defined strictly by biological criteria, whereas Lesbian, Gay, Bisexual, Transgender and Queer or are questioning their sexual identity - LGBTQ refers primarily to identities, that is, sexual orientation identities or gender identities. Some individuals (with or without somatic intersexuality) who develop gender dysphoria and experience their identity as being at variance with their originally assigned gender do indeed use intersex (between the sexes in literal translation) as an identity label. Most individuals with a somatic intersex condition, however, identify as female or male, that is, within the gender binary. In contrast, clinicians occasionally encounter a person with gender-identity variance without somatic intersexuality who tries to persuade them that she/he does in fact have a form of somatic intersexuality or may even self-administer cross-sex hormones, without disclosing it, to prove that point (authors unpublished observations). The term transgender is commonly applied to gender-identity variant individuals with a standard 46,XY or 46, XX karyotype andbefore sex-reassignment surgerythe respective male-typical or female-typical reproductive tract. By contrast, somatic intersexuality (regardless of the presence or absence of gender dysphoria) comprises a large number of diverse sex-chromosome, genetic, and hormonal variants, many of which cannot yet be definitively diagnosed in genetic terms. Three of the better known syndromes are (1) 46,XX congenital adrenal hyperplasia (CAH) with highly variable degrees of genital masculinization despite presence of ovaries and intact uterus and proximal vaginal tract; its cause is enzyme defects in the pathways of cortisol and aldosterone biosynthesis, the effects of which include excess prenatal and postnatal androgen production by the adrenal glands; (2) 46,XY androgen insensitivity with highly variable degrees of genital hypomasculinization despite normal or high-normal testicular androgen production because of reduced responsiveness of the androgen receptor; such patients usually lack a uterus and vaginal tract, because their testes produce normal amounts of anti-Mllerian hormones; (3) 46,XY 5-reductase-2 (5-R2) deficiency with normal masculinization of the internal genitalia but variable hypo masculinization of the external genitalia because of a genetically caused deficiency of the enzyme involved in the conversion of testosterone to dihydrotestosterone, the androgen required for masculinization of the external (but not internal) genitalia; patients with 5-R2 deficiency undergo very strong somatic virilization during puberty, when an isoenzyme of 5-R2 in another body compartment becomes activated. The transition to adulthood constitutes a particular challenge for patients with somatic intersexuality, because there are very few medical and mental health professionals specialized in the care of adults with such conditions. In the absence of skillfully planned services to assist in the transition from pediatric to adult care, many adult patients are reluctant to access providers they do not know or may encounter physicians who are not experienced with their conditions, resulting in insufficient and/or inadequate medical and mental healthcare. Additional problems may arise if gender dysphoria develops which occurs in patients with somatic intersexuality at a rate higher than in the non-DSD population, varies with syndrome type, severity, and initial gender assignment, and can happen at any phase of life after infancy. Thus, optimal care for patients with intersexuality involves an integrated interdisciplinary team approach. Most needed on the medical side is research on underlying genetics, optimal hormone treatment, and condition-specific best approaches to decisions regarding genital surgery, including techniques and timing. Identifying all genes involved in the development of intersexuality (involving both genes that encode transcription factors and regulatory genes) would permit more uniform genetic grouping of individuals with intersexuality, better targeting of medical treatment, and a more stringent description of condition-specific long-term medical and psychosocial outcomes. Further development of intersex-specific DNA microarrays or biochips is urgently needed to make such detailed genetic screening widely affordable. The findings would also contribute to clarifying the many steps involved in normative somatic sexual differentiation and the interaction of genetic factors (including epigenetic processes) therein. The endocrine management is particularly complex in individuals with CAH, especially 46,XX females, because of the difficulty of finding a balance between glucocorticoid replacement and the associated suppression of adrenal androgens, which affect growth, weight, somatic virilization, and insulin responsiveness. Despite exemplary development of respective evidence-based guidelines by the Endocrine Society, much more empirical work is required, and an updating of the guidelines is currently in progress. Systematic research work on hormone replacement in the many 46,XY syndromes of intersexuality is much more limited, and an authoritative and comprehensive set of guidelines is yet to be developed. Currently, the most controversial topic in intersex care is genital surgery for other than strictly medical indications (i.e., gender confirming or normalizing). Should such surgery be performed at all, given the risks involved to appearance and to urinary and sexual function? In view of the risks, should it be delayed until the patient has reached the age of consent? Or at least until the patient has demonstrated a stable gender identity, and no other risk factors for the development of gender dysphoriasuch as marked gender-atypical behavior, incongruent pubertal development, or disclosure of gender-incongruent features such as Y chromosomes in a patient raised as a girlare present or expected? And which surgical techniques are optimal at which developmental stage for the diverse genital configurations created by the many different intersex syndromes and their variations in severity? Gender-confirming genital surgery of patients with intersexuality is very different from the procedures most commonly used in transgender patients without somatic intersexuality, and published guidelines increasingly recommend limitation of genital surgery on individuals with intersexuality to surgeons or surgical centers with a relative large number of such patients and much experience with related surgical procedures. Endocrine and surgical treatments depend on the patients assigned gender. Gender assignment requires a complex decision process, taking into consideration the biological factors involved in the development of the condition in a given patient and the associated prognosis for future development of reproductive, sexual, gender, and psychological features as well as the (sub)cultural sex/gender ideologies of the parents. A major unresolved question is whether it will become possible to identify, through brain imaging or other means, biomarkers of the sexual differentiation attained by the brain of a newborn or a preschool child or an adolescent that can serve as a guide to initial gender assignment or as an indication for gender reassignment. In any case, a comprehensive approach can improve gender assignment in terms of minimizing the likelihood of developing gender dysphoria in the assigned gender but there will always be some patients who will question their gender or develop gender dysphoria. Given the paucity of intersex specialists, the overall organisation of both medical and psychosocial care for patients with intersexuality needs to be worked outincluding communication through telemedicine techniques between specialists at multidisciplinary centers of expertise and clinical practitioners elsewhere, the involvement of support groups and advocacy agencies, the deliberate planning of transition from pediatric to adult care, and the provision of specialized care for elderly patients with intersexuality, along with the dissemination of the necessary training procedures, preferably all within the theoretical framework of implementation science. While addressing the many specific details, the clinical team must never lose sight of the fact that their patients are human beings who are just facing some specific medical and psychosocial challenges and that the overall goal of professional intervention is to minimize societal stigma and to foster the development of healthy and happy adults with their self-esteem intact. The writer is former Head, Department of Medical Sociology, Institute of Epidemiology, Disease Control Research (IEDCR) E-mail: [email protected]