Disorders of Sexual Development
Section snippets
Disorders of sex development classification and etiologies
Disorders of sex development may result from a heterogeneous group of etiologies. The DSD nomenclature divides these etiologies into categories of 46XX DSD, 46XY DSD, Sex Chromosome DSD, Ovotesticular DSD, and 46XX Testicular DSD. Within each category specific diagnoses are made when possible (Table 1).
Approach to diagnosis
In the newborn period, in particular, when an infant is born with ambiguous genitalia reflecting a possible diagnosis of a DSD, there is felt a sense of urgency to provide the family with not only the specific diagnosis but in conjunction a gender assignment. This urgency arises from the cultural pressures that necessitate the usual announcement of “It's a boy” or “It's a girl” to friends, family, and colleagues. However, the complexities of diagnosis and gender assignment require time; it is
Management: gender assignment
Before discussing assignment of gender, one must understand the three components of psychosexual development. Gender identity refers to the intrinsic sense of oneself as female or male. Gender role refers to the set of behaviors typical of one gender or another, these will vary with context such as the surrounding culture. Sexual orientation refers to an individual's erotic responsiveness, that is the gender or genders to whom one is attracted (homosexual, heterosexual, bisexual). Gender
Surgery
When undertaken, feminizing genital surgery includes some or all of the following: clitoral surgery for clitoral hypertrophy, urogenital sinus mobilization if present, labioplasty, neovaginal construction, and possible gonadectomy in XY containing karyotypes.
Clitoral surgery has evolved considerably. Originally surgery to reduce the size of the clitoris involved clitoral resection, owing to its obvious severe impact on sexuality, clitoral recession replaced resection in the 1980s.29, 30
Gonadectomy
Gonadectomy is required in some 46XY DSD conditions for two main reasons: risk of malignancy and risk of ongoing virilization with continued androgen exposure (with female gender assignment).
Dysgenetic gonads or intra-abdominal testes carry a varying risk of malignancy. DSD patients are at increased risk of developing seminomas of the testes and dysgerminomas in dysgenetic gonads.39 Gonadoblastomas may occur in the dysgenetic gonads of children.40 Less frequent gonadal malignancies include
Medical
The discussion of the steroid management of the most common cause of ambiguous genitalia, congenital adrenal hyperplasia, is beyond the scope of this article. Principles of hormone replacement therapy will be presented for DSD diagnoses with female gender. The goals of hormone replacement therapy are not only to initiate and maintain secondary sexual characteristic development (including uterine growth) but also to allow for psychosexual development. Bone health will benefit from sex steroid
Outcomes
The ideal information to guide policies on the management of individuals with DSD is long-term outcome data covering all aspects of quality of life, sexuality, fertility, and psychosocial functioning. There are challenges with regard to interpreting the information that is beginning to become available. The most marked is that management has evolved; surgical techniques have changed; and interprofessional teams recognizing the importance of psychological support, family-centered care,
Gender identity
Gender dysphoria is present in 46XY DSD conditions with normal gonadal function and less commonly in 46XX DSD medical conditions including CAH and in other DSD conditions. Gender dysphoria is more common with female gender assignment than male gender assignment, although dissatisfaction with male sex of rearing can be seen.20, 21, 22
Several studies have assessed the degree of gender dysphoria and gender change in adolescent and adult women with CAH.20, 22, 53 This group of individuals would
Surgical outcomes
In the past several years, an increasing number of international clinics and DSD teams have published on the outcomes of childhood surgery for the women they care for. Recognition exists that the cosmesis of external genitalia may not reflect the function of the genitalia. Studies that look at interim results, with only short-term follow-up into childhood may not reflect or correlate with longer term results but at the present time are the only measures available for assessing newer surgical
Psychosexual outcomes/quality of life measures
Quality of life for women includes aspects of intimacy with partners, arousal and sexual function, as well as self-esteem, social functioning, and mental health. Recently, quality-of-life studies are being reported on women with DSD diagnoses compared with either illness controls or population controls. Women with DSD may report delayed sexual milestones, fewer partnerships and sexual experiences, and a lower level of arousal.53, 54, 62 Overall lower quality of life, higher anxiety, higher
Disclosure
Disclosure begins with the family at the time of the diagnosis and assessment of their newborn with a DSD and should be considered a lifelong ongoing process that evolves along a developmental time line. The diagnosis of DSD is both challenging to understand and challenging to explain; however, the health care team should consider themselves as having a role in preparing the family and the child/adolescent to receive this diagnosis when they are cognitively and psychologically prepared. In
Summary and future direction
Patients with DSD are infrequently encountered with an incidence 1:5500.2 Their complex management must address medical, surgical, and psychosexual needs of the individual patient. Evolving information suggests that thoughtful, flexible, family-centered care by specialized interprofessional teams may provide the optimal environment for care. The awareness that current management cannot eliminate all adverse outcomes (eg, gender dysphoria, surgical complications) should drive ongoing research
Acknowledgment
I acknowledge the dedicated team of health care professionals who make up the Multidisciplinary Urogenital Clinic at The Hospital for Sick Children from whom I have learned so much: Riyanna Babul-Hirji, MS, Darius Bagli, MD, Susan Bradley, MD, David Chitayat, MD, Walid Farhat, MD, Genevieve Kilman, BA, CCLS, Armando Lorenzo, MD, Barb Neilson, MSW RSW, J.L. Pippi Salle, MD, PhD, Dianne Wherret, MD, and Ken Zukker, PhD. A special thank you to Barb Neilson for her comments on the article.
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Cited by (29)
Metzincin metalloproteases in PGC migration and gonadal sex conversion
2023, General and Comparative EndocrinologyCitation Excerpt :At same time, their extracellular matrix (ECM) must also go through dramatic remodeling and differentiation for proper gonad development (Marty et al., 2003; Beckman and Feuston, 2003; Maack and Segner, 2003; King et al., 1968; Hirsh et al., 1976; McLaren, 1991; Yildirim et al., 2020). Disruption of these complex processes via genetic or environmental causes typically leads to disorders of sexual development (DSDs) and infertility in humans (Allen, 2009; Öçal, 2011; Juul et al., 2014; Abrao et al., 2013; Roupa et al., 2009; Ferlin et al., 2006; Ferlin et al., 2006; Galani et al., 2008; Zuccarello et al., 2007) but can result in sex reversal in other animal species including fish (Baroiller and D’Cotta, 2020; Carter et al., 2019; Dranow et al., 2013; Dranow et al., 2016; Sakae et al., 2020). Most studies in gonad development and sex determination were focused on the roles of transcription factors and restricted to early sex determination and differentiation (Mamsen et al., 2017; Nagahama, 2005; Hayes, 1998; Devlin and Nagahama, 2002; Nagahama et al., 2021; Wilhelm et al., 2007).
Patients with disorders of sex development undergoing surgical treatment: A psychosocial evaluation in adolescence
2021, Archives de PediatrieCitation Excerpt :Disorders of sex development (DSD) include congenital conditions in which the development of gonadal, chromosomal, or anatomic sex is different from normal, with these differences potentially incompatible with each other. These disorders are mostly apparent at birth, displaying as ambiguous genitalia of the infant [1]. Worldwide it is estimated to occur in one of every 4500–5000 births [2].
Congenital abnormalities of the female reproductive tract: Anomalies of the Vagina, Cervix, Uterus, and Adnexa
2021, Comprehensive GynecologyDisorders of sex development
2019, Clinical Molecular Medicine: Principles and PracticeFrequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data
2018, Cancer EpidemiologyCitation Excerpt :In addition, transgender people who undergo gender affirmation treatment may receive high doses of sex steroid hormones for extended periods of time; the carcinogenicity of hormone therapy in this context is also unclear [8,9]. The term DSD refers to a heterogeneous group of conditions affecting the development of sex chromosomes, gonads, or anatomic sex [10,11]. DSD can be identified at birth by the presence of atypical genitalia, during adolescence by the absence of or contra-sexual pubertal development, or in adulthood following discovery of fertility problems.
Intersexuality in aquatic invertebrates: Prevalence and causes
2017, Science of the Total EnvironmentCitation Excerpt :At present OT-DSD is considered an intersex condition in which an individual is born with ovarian and testicular tissue. Due to advances in scientific knowledge, the term hermaphroditism is no longer confused with intersex, as the former refers only to a specific phenotypic characteristic of sex organs whilst the latter to a more complex mixture of phenotypic and genotypic displaying, often involving genital ambiguity, and even combinations of chromosomal genotype and sexual phenotype other than XY-male and XX-female (Allen, 2009). Most of the Earth's flowering plants are hermaphrodite (94%), however it is a rare condition among animals, excluding insects.