Disorders of sex development

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Disorders of sex development
Other namesDisorders of sex differentiation, variations of sex characteristics [1]
Specialty Medical genetics

Disorders of sex development (DSDs), also known as differences in sex development or variations in sex characteristics (VSC), [2] [3] are congenital conditions affecting the reproductive system, in which development of chromosomal, gonadal, or anatomical sex is atypical. [4] DSDs is a clinical term used in some medical settings for what are otherwise referred to as intersex traits. The term was first introduced in 2006 and has not been without controversy.

Contents

DSDs are subdivided into groups in which the labels generally emphasize the karyotype's role in diagnosis: 46,XX; 46,XY; sex chromosome; XX, sex reversal; ovotesticular disorder; and XY, sex reversal. [5]

Overview

Variations of Sex Characteristics (VSC) Chart Vsc chart.png
Variations of Sex Characteristics (VSC) Chart

DSDs are defined as "any problem noted at birth where the genitalia are atypical in relation to the chromosomes or gonads". [6] There are several types of DSDs, and their effect on the external and internal reproductive organs varies greatly.

A frequently used, casual social adjective for people with DSDs is "intersex".[ citation needed ] Urologists were concerned that terms like intersex, hermaphrodite, and pseudohermaphrodite were confusing and pejorative with respect to humans. This led to the Chicago Consensus, recommending a new terminology based on the umbrella term disorders of sex development. [7] [8] Other than disorders of sex development, another term is congenital conditions of sex development (CCSD). Since 2006, people who were previously incorrectly categorized as hermaphrodites are now labelled as having ovotesticular syndrome.

DSDs are divided into the following categories, emphasizing the karyotype's role in diagnosis: [9] [10]

Genital anatomy

The Quigley scale is a method for describing genital development in AIS. Quigley scale for androgen insensitivity syndrome.jpg
The Quigley scale is a method for describing genital development in AIS.

The penis (males) and clitoris (females) have a common origin, both arising from an embryonic structure called the primordial phallus. In typical males, the urethra is located at the tip of the penis, while in typical females the urethra is located below the base of the clitoris. [11] It is also possible to have a urethral opening located along the shaft; this condition is known as hypospadias. [12]

Management of DSDs

Due to the significant and life-long impacts that DSDs can have on patients and their families, [13] it is widely accepted that children with DSDs should be managed by an experienced multidisciplinary team. [14] Health care providers generally agree that children with DSDs should be notified early. [15]

Appropriate and conservative medical intervention and age-appropriate child involvement in the treatment plan contribute greatly to successful outcomes for the entire range of DSDs. [16] [17]

Conditions

Organizations

Clinical networks and organizations

DSD-TRN

The Differences of Sex Development-Translational Research Network (DSD-TRN) is based in the United States and aims to improve DSD care across the United States. [67]

I-DSD

The International-Differences of Sex Development (I-DSD) is a research organization in Europe. This organization connects medical and research centers internationally in an effort to improve clinical practice, research, and general understanding of differences of sex development. [68] I-DSD regularly hosts a symposium to provide updates on current care in DSD internationally, facilitate networking for those in DSD Care, and promote high quality DSD research. [69]

Patient support and advocacy organizations

Notable patient support and advocacy organizations include:

Africa

Asia

Europe

Latin America

North America

Oceania

International

Controversy

Terminology

The term disorders of sex development has generally been accepted by the medical community, as well as being a popular term in academic literature. [71] However, the term is not universal among patients or support groups. [72] One study stated that it can affect individuals covered by the description in a negative way, and that the terminology might impact choice and utilization of health care providers. [73] Another study found that most affected individuals did not find the term offensive. [74] The ICD-11, which is the World Health Organization's international guide to medical coding (effective as of January 1, 2022), references DSDs as intersex traits or conditions, as do some medical journals. [75] The Council of Europe [76] and Inter-American Commission on Human Rights [77] have called for a review of medical classifications that unnecessarily medicalize intersex traits. [76] [77] [78]

The DSD as a model was advocated for by intersex advocates to include all variation of atypical sexual development. Specifically the DSD exists as replacement for the "optimum gender rearing model," which was the standard model for individuals with atypical sexual development. This model stated goal was to assign a gender binary, usually female via non-consensual medicalization, often via the falsification of medical records. After the publication of individuals who had undergone the OGR model and had gone through serious physiological distress, (such as David Reimer), the model was discredited. The term "disorders of sexual development" was chosen to reflect the variation of sexual development over differences which effects all individuals, this however has been controversial, with many instead opting for "differentiation" or "variation." [79]

Sociological research in Australia on 272 "people born with atypical sex characteristics," published in 2016, found that 3% of respondents used the term "disorders of sex development" or "DSD" to define their sex characteristics, while 21% use the term when accessing medical services. In contrast, 60% used the term "intersex" in some form to self-describe their sex characteristics. [80] U.S. research by the Lurie Children's Hospital, Chicago, and the AIS-DSD Support Group (now InterConnect Support Group) published in 2017 found that "disorders of sex development" terminology may negatively affect care, give offense, and result in lower attendance at medical clinics. [81] [82]

A "dsd-LIFE" study in 2020 found that around 69% of 1,040 participants reported that DSD applied to their condition or that they felt neutral about the term, with most participants preferring terms that were specific to their somatic condition. [74]

Human rights and community concerns

The term DSD (and particularly its association with medical disorders) has been controversial. The argument over terminology reflects a deeper disagreement over the extent to which intersex conditions require medical intervention, the appropriateness of certain interventions, and whether physicians and parents should make irreversible treatment decisions on behalf of young children if the condition is not life-threatening.

National and international medical classifications which pathologise variations in sex characteristics should be reviewed with a view to eliminating obstacles to the effective enjoyment, by intersex persons, of human rights, including the right to the highest attainable standard of health. [76]

Clinical disagreements about the term

While the 2006 clinical consensus statement that introduced the term, [4] its 2016 update, [47] included some sex chromosome anomalies within the term DSD, the inclusion of those conditions is opposed by some clinicians.[ citation needed ] Medical historian David Griffiths has identified continued controversy about the relationship between sex chromosome variations and intersex/DSD classifications. [101]

Similarly, some clinicians have proposed that congenital adrenal hyperplasia be excluded. [102] Human rights advocate Morgan Carpenter has remarked that this proposal appears motivated by support for contentious medical interventions. [103]

A member of the legal committee for the World Professional Association for Transgender Health and co-founder of the Australian and New Zealand Professional Association for Transgender Health has described "transsexualism" as "an intersex condition and a disorder of sexual development therapeutically medically treated by hormonal therapy and Genital Reassignment Surgery". [104] Such views are contested. [105]

People with DSDs competing in sporting events

There is particular contention around female-presenting athletes with DSDs (which can cause an elevated level of testosterone) competing in female-only sports events. [106]

World Athletics claimed that while 46 XY DSD occurs in roughly 1 in 20,000 people in the general population, it is found in about 7 in 1,000 elite female athletes (with a prevalence 140 times higher) arguing that this offers significant performance advantage. Within the scientific community there is ongoing debate over whether any physiological advantage, in fact, exists. [107]

See also

Related Research Articles

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5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by a mutation in SRD5A2, a gene encoding the enzyme 5α-reductase type 2 (5αR2). The condition is rare, affects only genetic males, and has a broad spectrum.

<span class="mw-page-title-main">Androgen insensitivity syndrome</span> Medical condition

Androgen insensitivity syndrome (AIS) is a condition involving the inability to respond to androgens, typically due to androgen receptor dysfunction.

<span class="mw-page-title-main">XY gonadal dysgenesis</span> Medical condition

XY complete gonadal dysgenesis, also known as Swyer syndrome, is a type of defect hypogonadism in a person whose karyotype is 46,XY. Though they typically have normal vulvas, the person has underdeveloped gonads, fibrous tissue termed "streak gonads", and if left untreated, will not experience puberty. The cause is a lack or inactivation of an SRY gene which is responsible for sexual differentiation. Pregnancy is sometimes possible in Swyer syndrome with assisted reproductive technology. The phenotype is usually similar to Turner syndrome (45,X0) due to a lack of X inactivation. The typical medical treatment is hormone replacement therapy. The syndrome was named after Gerald Swyer, an endocrinologist based in London.

<span class="mw-page-title-main">Virilization</span> Biological development of male sex characteristics

Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens.

<span class="mw-page-title-main">Intersex medical interventions</span> Performed to modify atypical or ambiguous genitalia

Intersex medical interventions (IMI), sometimes known as intersex genital mutilations (IGM), are surgical, hormonal and other medical interventions performed to modify atypical or ambiguous genitalia and other sex characteristics, primarily for the purposes of making a person's appearance more typical and to reduce the likelihood of future problems. The history of intersex surgery has been characterized by controversy due to reports that surgery can compromise sexual function and sensation, and create lifelong health issues. The medical interventions can be for a variety of reasons, due to the enormous variety of the disorders of sex development. Some disorders, such as salt-wasting disorder, can be life-threatening if left untreated.

<span class="mw-page-title-main">History of intersex surgery</span>

The history of intersex surgery is intertwined with the development of the specialities of pediatric surgery, pediatric urology, and pediatric endocrinology, with our increasingly refined understanding of sexual differentiation, with the development of political advocacy groups united by a human qualified analysis, and in the last decade by doubts as to efficacy, and controversy over when and even whether some procedures should be performed.

<span class="mw-page-title-main">Clitoromegaly</span> Unusually large clitoris

Clitoromegaly is an abnormal enlargement of the clitoris that is mostly congenital; it is otherwise acquired through deliberately induced clitoral enlargement e.g. body modification by use of anabolic steroids, including testosterone. It can happen as part of a gender transition. It is clinically distinguishable from normal enlargement of the clitoris seen during sexual arousal.

Ovotesticular syndrome is a rare congenital condition where an individual is born with both ovarian and testicular tissue. It is one of the rarest DSDs, with only 500 reported cases. Commonly, one or both gonads is an ovotestis containing both types of tissue. Although it is similar in some ways to mixed gonadal dysgenesis, the conditions can be distinguished histologically.

Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.

<span class="mw-page-title-main">Partial androgen insensitivity syndrome</span> Medical condition

Partial androgen insensitivity syndrome (PAIS) is a condition that results in the partial inability of the cell to respond to androgens. It is an X linked recessive condition. The partial unresponsiveness of the cell to the presence of androgenic hormones impairs the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is clinically significant only when it occurs in individuals with a Y chromosome. Clinical features include ambiguous genitalia at birth and primary amenhorrhoea with clitoromegaly with inguinal masses. Müllerian structures are not present in the individual.

<span class="mw-page-title-main">Sexual differentiation in humans</span> Process of development of sex differences in humans

Sexual differentiation in humans is the process of development of sex differences in humans. It is defined as the development of phenotypic structures consequent to the action of hormones produced following gonadal determination. Sexual differentiation includes development of different genitalia and the internal genital tracts and body hair plays a role in sex identification.

Pseudohermaphroditism is an outdated term for when an individual's gonads were mismatched with their internal reproductive system and/or external genitalia. The term was contrasted with "true hermaphroditism", a condition describing an individual with both female and male reproductive gonadal tissues. Associated conditions includes Persistent Müllerian duct syndrome and forms of androgen insensitivity syndrome.

<span class="mw-page-title-main">Complete androgen insensitivity syndrome</span> Medical condition

Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. As such, the insensitivity to androgens is only clinically significant when it occurs in individuals who are exposed to significant amounts of testosterone at some point in their lives. The unresponsiveness of the cell to the presence of androgenic hormones prevents the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does allow, without significant impairment, female genital and sexual development in those with the condition.

<span class="mw-page-title-main">Intersex</span> Atypical congenital variations of sex characteristics

Intersex people are individuals born with any of several sex characteristics, including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical binary notions of male or female bodies".

Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism or primary gonadal failure, is a condition which is characterized by hypogonadism which is due to an impaired response of the gonads to the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and in turn a lack of sex steroid production. As compensation and the lack of negative feedback, gonadotropin levels are elevated. Individuals with HH have an intact and functioning hypothalamus and pituitary glands so they are still able to produce FSH and LH. HH may present as either congenital or acquired, but the majority of cases are of the former nature. HH can be treated with hormone replacement therapy.

<span class="mw-page-title-main">Leydig cell hypoplasia</span> Medical condition

Leydig cell hypoplasia (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 individuals with XY chromosomes. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism, hypergonadotropic hypogonadism, reduced or absent puberty, and infertility.

<span class="mw-page-title-main">Eric Vilain</span> French-American physician-scientist

Eric Vilain is a physician-scientist and professor in the fields of differences of sex development (DSDs) and precision medicine. He is the Associate Vice Chancellor for Scientific Affairs at the University of California, Irvine Health Affairs and also the director of the UCI Institute for Clinical and Translational Science. He previously was the director of the Center for Genetic Medicine Research at Children's National Medical Center and the chair of the Department of Genomics and Precision Medicine at the George Washington University School of Medicine & Health Sciences in Washington, D.C. Vilain is a fellow of the American College of Medical Genetics, serves on the International Olympic Committee's Medical Commission, and sits on the Board of Scientific Counselors for the National Institute of Child Health and Human Development (NICHD).

Sexual anomalies, also known as sexual abnormalities, are a set of clinical conditions due to chromosomal, gonadal and/or genitalia variation. Individuals with congenital (inborn) discrepancy between sex chromosome, gonadal, and their internal and external genitalia are categorised as individuals with a disorder of sex development (DSD). Afterwards, if the family or individual wishes, they can partake in different management and treatment options for their conditions.

<span class="mw-page-title-main">Definitions of intersex</span>

Various criteria have been offered for the definition of intersex, including ambiguous genitalia, atypical genitalia, and differential sexual development. Ambiguous genitalia occurs in roughly 0.05% of all births, usually caused by masculinization or feminization during pregnancy, these conditions range from full androgen insensitivity syndrome to ovotesticular syndrome.

<span class="mw-page-title-main">Intersex healthcare</span> Healthcare for intersex people throughout their lives

Intersex healthcare differs from the healthcare of endosex people due to stigma and potential complications arising from their bodily variations. Intersex healthcare is impacted by a history of concealing information from patients and medically unnecessary surgeries that continue to be performed. 1.7% of the general population is estimated to be intersex. Healthcare for intersex people can include treatments for one's mental, cognitive, physical, and sexual health. The needs of intersex people vary depending on what intersex variation they have.

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