Ovarian Development Disorders
Simple 46,XX Gonadal Dysgenesis
Pubertal abnormalities become apparent due to impaired feminization.
46,XX Ovotesticular DSD and 46,XX Testicular DSD
In extremely rare cases, ovarian tissue in 46,XX individuals may contain testicular elements (46,XX ovotesticular DSD), or the gonads may develop functional testicular tissue (46,XX testicular DSD).
Androgen Excess
If hyperandrogenemia occurs before 12 weeks of gestation, clitoromegaly resembling a micropenis and partial or near-complete fusion of the labia are observed. When it occurs after 12 weeks of gestation, only clitoromegaly is typically seen. This condition includes the following causes:
21-Hydroxylase Deficiency
Three clinical subtypes exist. The salt-wasting type is the most common, with affected infants exhibiting severe feeding difficulties, vomiting, diarrhea, dehydration, hyponatremia, hyperkalemia, and metabolic acidosis within days of birth. Patients with this subtype also often exhibit more severe virilization of the external genitalia. The second most common presentation is the simple virilizing type. The non-classical CYP21A2 deficiency type has a lower incidence.
11β-Hydroxylase Type 1 Deficiency
Clinical features include low-renin hypertension, with some patients presenting hypokalemia. Progressive virilization, clitoromegaly, and labial fusion may be observed.
3β-Hydroxysteroid Dehydrogenase Type II Deficiency
Affected female infants present with glucocorticoid deficiency and mild clitoromegaly at birth, with or without salt-wasting.
Aromatase Deficiency
Infants may present at birth with clitoromegaly, varying degrees of posterior labial fusion, labioscrotalization, or a single vaginal opening. Aromatase deficiency should be strongly considered in all 46,XX infants who exhibit masculinization at birth, particularly after excluding 21-hydroxylase deficiency.
Management of Disorders of Sex Development (DSD)
Treatment for patients with DSD addresses both secondary sexual development and reproductive health. Most individuals with DSD present abnormal external genitalia at birth, making the identification of gender a critical early decision. Appropriate gender assignment is ideally determined by a multidisciplinary team, including endocrinologists, surgeons, obstetricians, pediatricians, and psychologists. Following gender assignment, early genital reconstructive surgery is typically recommended to support normal psychosexual development.
Hormonal therapy constitutes the primary treatment during puberty and adulthood due to the common presence of sex hormone deficiencies in DSD patients. Gonadotropin replacement, such as human chorionic gonadotropin (HCG), may be used in male patients with gonadotropin deficiency. Female patients can undergo cyclic replacement therapy with estrogen and progestin to establish artificial menstrual cycles.
In patients with congenital adrenal hyperplasia, glucocorticoid replacement therapy can significantly alleviate masculinization in females.
Fertility is often significantly impaired among individuals with DSD, and assisted reproductive techniques may be required. In some cases, fertility is entirely lost.
Psychological support also plays a crucial role in the management of DSD patients, addressing both emotional well-being and quality of life.