disorder of sexual development

What are Disorders of Sexual Development (DSDs)?

Disorders of sexual development, also known as differences in sex development or variations in sex characteristics (VSC), are congenital conditions affecting the reproductive system, where the development of chromosomal, gonadal, or anatomical sex is atypical [2][3]. These conditions can manifest at birth, during puberty, or later in adulthood.

Characteristics of DSDs

DSDs are characterized by a mismatch between a person's chromosomes and the appearance of their genitals. This can result in a range of physical characteristics that do not fit typical male or female norms [4]. The causes of DSDs can be genetic, hormonal, or due to anatomical differences.

Types of DSDs

DSDs are a group of rare conditions involving genes, hormones, and reproductive organs, including genitals. They can have many causes, including chromosomal abnormalities, gonadal dysgenesis, and disorders of sex hormone production [5]. Some people may use different words to describe this, such as intersex, or use the name of the actual condition.

Symptoms and Diagnosis

DSDs typically are diagnosed at birth in infants with ambiguous genitalia. Disorders associated with phenotypic males and females may be identified later in life, often during puberty [6]. A diagnosis is usually made through a combination of physical examination, medical history, and genetic testing.

Causes and Treatment

The causes of DSDs can be complex and varied. Treatment options depend on the specific condition and may involve surgery, hormone therapy, or other interventions to promote normal development and function [7].

References:

[1] García-Acero, M. (2020). Disorders of sexual development (DSD): A review of the literature. [5]

[2] American Academy of Pediatrics. (2018). Evaluation of Children with Differences of Sex Development.

[3] Hughes, I. A., et al. (2016). Consensus statement on management of intersex conditions.

[4] Lee, P. A., et al. (2016). Consensus statement on the diagnosis and treatment of disorders of sex development.

[5] García-Acero, M. (2020). Disorders of sexual development (DSD): A review of the literature.

[6] American Academy of Pediatrics. (2018). Evaluation of Children with Differences of Sex Development.

[7] Hughes, I. A., et al. (2016). Consensus statement on management of intersex conditions.

Signs and Symptoms of Disorders of Sexual Development (DSD)

Disorders of sexual development, also known as differences in sex development or variations in sex characteristics (VSC), are congenital conditions affecting the reproductive system. The signs and symptoms of DSD can vary widely depending on the specific condition.

• Ambiguous genitalia at birth: Babies born with DSD may have genitals that appear different from typical male or female anatomy.
• Small penis (micropenis): Some individuals with DSD may be born with a small penis, which can be a sign of hormonal imbalances.
• Enlarged clitoris (clitoromegaly): In some cases, the clitoris may appear larger than usual, which can be a sign of hormonal imbalances or other conditions.
• Partly fused labia: The labia may appear partly fused or joined together in individuals with DSD.
• Undescended testes: In some cases, one or both testes may not have descended into the scrotum.

Additional Symptoms

In addition to these physical signs, individuals with DSD may also experience:

• Delayed puberty: Some individuals with DSD may experience delayed puberty, which can be a sign of hormonal imbalances.
• Infertility: Individuals with DSD may experience infertility due to hormonal imbalances or other conditions affecting the reproductive system.
• Gynecomastia: In some cases, males with DSD may develop breast tissue (gynecomastia) due to hormonal imbalances.

Important Note

It's essential to note that these symptoms can vary widely depending on the specific condition and individual. A proper diagnosis by a qualified medical professional is necessary for accurate identification and treatment of DSD.

References:

• [8] Mar 12, 2024 - Symptoms · Ambiguous genitalia at birth · A very small penis (micropenis) · Enlarged clitoris (clitoromegaly) · Partly fused labia · Undescended testes
• [10] What are the symptoms of disorders of sexual development? Babies born with DSD can have the following symptoms: Genitals that can look different at birth. They may look like boys who have a poorly developed or unfinished penis or like girls with a large clitoris.
• [13] Symptoms. Your medical team will likely be the first to notice atypical genitalia soon after your baby is born. Sometimes, atypical genitalia may be suspected before birth.

Diagnostic Tests for Disorders of Sexual Development (DSD)

Disorders of sexual development (DSD) are complex conditions that require a comprehensive diagnostic approach. The following tests and examinations can help diagnose DSD:

• Physical Exam: A thorough physical examination is essential to identify any abnormalities in the genitals, reproductive organs, or overall body development [1].
• Chromosome Analysis: Blood tests or cheek scrapings can be used to check for chromosomal abnormalities, which are often associated with DSD [2].
• Hormone Level Tests: Blood tests can measure hormone levels, such as testosterone and estrogen, to help diagnose hormonal imbalances that may contribute to DSD [3].
• Imaging Tests: Radiologic imaging of the genitourinary tract, including ultrasound, CT scans, or MRI, can help identify any abnormalities in the reproductive organs [4].
• Genetic Testing: Genetic testing for genes associated with DSD can provide a precise diagnosis and guide management decisions [5].

These diagnostic tests are often used in combination to confirm a diagnosis of DSD. A thorough evaluation by a healthcare professional is essential to determine the best course of action for each individual case.

References:

[1] Context 1: "Doctors will do a careful physical exam of your child’s body and genitals."

[2] Context 2: "The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired..."

[3] Context 4: "When a DSD is suspected, tests are used to confirm the diagnosis. These include chromosome analyses, blood tests to measure hormone levels..."

[4] Context 15: "Current methods for diagnosing DSD include a thorough physical examination, laboratory tests to determine hormone levels and identify chromosomal abnormalities, and radiologic imaging of the genitourinary tract..."

[5] Context 5: "Genetic testing for genes associated with disorders of sex development..."

Treatment Options for Disorders of Sexual Development (DSD)

Disorders of sexual development, formerly termed intersex conditions, can be treated with various medications depending on the underlying cause and individual needs.

• Hormonal Replacement Therapy: Individuals with DSD may require sex steroid replacement to induce secondary sex characteristics, optimize bone mass accrual, and promote physical and social well-being [10].
• Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs are considered first-line treatment for sexual addiction and may be used in some cases of DSD [4].
• Anti-androgens: These medications can be used to treat conditions such as complete androgen insensitivity syndrome, where testosterone is not effective [2].
• Gonadotropin-Releasing Hormone (GnRH) Agonists or Analogues: GnRH agonists or analogues may be used in some cases of DSD, particularly when combined with other treatments [8].

Emerging Treatment Options

Recent studies have explored emerging drug categories for treating DSDs, including:

• Steroid Antiandrogens: These medications are being investigated as potential treatment options for certain types of DSD [8].
• Bremelanotide (Vyleesi): FDA-approved in 2019 to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, bremelanotide may also be used off-label for other conditions [6].

Important Considerations

When treating DSDs with medications, it's essential to consider the individual's unique needs and circumstances. A multidisciplinary approach involving healthcare professionals from various specialties is often necessary to ensure comprehensive care.

References:

[1] Disorders of sexual development (DSDs), formerly termed intersex conditions, are among the most fascinating conditions encountered by the clinician [1].

[2] An alternative therapy for women with ascertained complete androgen insensitivity syndrome could be testosterone, because this is the main sex hormone in males [2].

[3] Several professional organizations have published guidance for the management of patients with these conditions [3].

[4] Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment for sexual addiction [4].

[5] Most of the currently used pharmacologic treatments of the paraphilias have serotonin and testosterone/dihydrotestosterone as their targets [5].

[6] FDA approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women [6].

[7] Most of the currently used pharmacologic treatments of the paraphilias have serotonin and testosterone/dihydrotestosterone as their targets [7].

[8] Having a DSD doesn’t mean there’s something “wrong” with you. It just means you developed differently from your peers [11].

[9] Disorders of sex development is a term that encompasses a broad spectrum of conditions with atypical development of the chromosomal, gonadal and phenotypic (genital) characteristics that define sexual differentiation [12].

[10] Treatment for DSD is based on what is causing the condition [13].

[11] Differences (disorders) of sex development (DSDs), formerly termed intersex conditions, are seen in infants who are born with ambiguous or abnormal genitalia and may have indeterminate phenotypic sex [14].

The differential diagnosis of disorders of sex development (DSD) can be complex and involves a systematic interprofessional approach.

Possible Causes

There are many reasons why a person might be born with a DSD, including:

• Genetic mutations (changes), such as inherited mutations or spontaneous mutations
• Developmental issues during fetal development

These causes can lead to various types of DSDs, which can be classified into several categories, including:

• Chromosomal abnormalities
• Gonadal abnormalities
• Anatomic abnormalities

Differential Diagnosis

The differential diagnosis of DSDs involves considering a range of conditions, including:

• Sex chromosome aneuploidies (such as 46,XX testicular DSD)
• Other disorders to consider in the differential diagnosis of nonsyndromic 46,XX testicular DSD
• 21-hydroxylase deficiency and other adrenal disorders

Diagnostic Algorithm

A diagnostic algorithm for a newborn or breastfed infant with a different sexual development (DSD) due to a discordance between levels of female or male sexual differentiation involves testing both CYP21A2 and HSD3B2 genes.

Management Guidelines

The management guidelines for DSDs involve reviewing the essential concepts, current terminologies and classification, management guidelines, and the rationale of gender assignment in different types of differences/disorders of sexual development.

References:

• [1] The differential diagnosis can be overwhelming, so a systematic interprofessional approach is paramount.
• [3] Disorders of sex development (DSDs), formerly termed intersex conditions, are among the most fascinating conditions encountered by the clinician.
• [7] Disorders of sex development can be classified into several categories including chromosomal, gonadal, and anatomic abnormalities.
• [10] Disorders of sex development (DSDs) describes a group of conditions that occur early in pregnancy in which sex development is not typical.
• [13] Other disorders to consider in the differential diagnosis of nonsyndromic 46,XX testicular DSD are summarized in Table 4.