Female pseudohermaphroditism is a congenital anomaly of the reproductive system, in which the sex glands are formed according to the female type, and external signs to a lesser or greater extent – according to the male. Disease is characterized by the structure of the external genitals of the heterosexual type, delayed female puberty, virilization. It is diagnosed during the examination of the genitals, cytogenetic and hormonal studies, ultrasound. Treatment includes steroid HRT, reconstructive intimate plastic surgery.
The sex of a person is differentiated by sex chromosomes and sex chromatin, sex glands, external genitals, secondary sexual characteristics and form of behavior. The combination of signs of both sexes in humans indicates hermaphroditism; in the case of pseudohermaphroditism (“pseudo” – false), heterosexuality concerns only the external genitalia. In this case, gender is determined by the structure and function of the sex glands (testicles – male, ovaries – female), and cases are many times less common than male.
Patients with female pseudohermaphroditism have a female set of chromosomes (46XX), vagina, ovaries, uterus, fallopian tubes; however, the external genitals are of an intermediate type and secondary sexual characteristics more characteristic of the male body (physique, hairline, voice timbre). Disorders of the development of external genitalia can be combined with abnormalities of the urethra and rectum.
Establishing gender identity can be difficult due to the uncertainty of the manifestations of the disease. Early differential diagnosis is important for the correct determination of gender, the effectiveness of further treatment, and the psychosocial adaptation of the child.
In the early stages of development, the embryo has indifferent rudiments of the genital glands, male and female genital ducts. Only at 8-10 weeks of embryogenesis, under the influence of genetic and epigenetic factors, sexual differentiation of the reproductive system occurs, with the distortion of which female pseudohermaphroditism can develop.
The causes are genetic anomalies or the effect of damaging factors on the embryo (endocrine diseases of the mother, the mother’s intake of androgens, synthetic progesterones in the first trimester of pregnancy, alcohol, narcotic, chemical intoxication, radiation). Genetic anomalies leading to the development of female pseudohermaphroditism are manifested by adrenogenital syndrome, which disrupts the process of maturation of the reproductive system.
Most often, female pseudohermaphroditism reveals a lack of the enzyme 21-hydroxylase, which is necessary for the production of the most important adrenal hormones – aldosterone and cortisol. Their deficiency during embryogenesis leads to a compensatory increase in ACTH secretion, the development of hyperplasia of the adrenal cortex and increased synthesis of male sex hormones – androgens that cause virilization in girls. Severe forms of adrenogenital syndrome in female pseudohermaphroditism can lead to the development of acute adrenal insufficiency and death.
Less often, female pseudohermaphroditism of extrarenal genesis is observed: when a pregnant woman receives androgens and progestins with a side androgenic effect; if the mother has an androgen-secreting tumor – adrenoblastoma or luteoma.
The distortion of the differentiation of the genitals in female pseudohermaphroditism leads to the birth of a child with an indeterminate gender and to errors in the identification of the sex of the newborn. In most girls, female pseudohermaphroditism is immediately manifested by the heterosexual structure of the external genitals, similar to hypospadias and bilateral cryptorchidism. Female pseudohermaphroditism is characterized by hypertrophy of the clitoris (enlargement and similarity to the penis); closure of the vaginal opening, fusion of the labia majora (from partial to complete – in the form of a scrotum); signs of urethral virilization of varying severity (displacement of the external opening of the urethra to the clitoris, urogenital sinus).
The presence of adrenogenital syndrome and female pseudohermaphroditism may indicate the appearance of symptoms of hypertension or dehydration during the newborn period. Without treatment of this disease, during the first years of life, the progression of virilization, rapid somatic maturation with premature overgrowth of epiphyseal slits and the development of stunting is observed in sick girls. During puberty, there is a delay in sexual development according to the female type, the absence of a menstrual cycle, a decrease in the timbre of the voice, the appearance of acne, excessive hair growth (hirsutism), an increase in muscle mass.
If an anomaly of the genitals is detected in a newborn in order to confirm or exclude the diagnosis of female pseudohermaphroditism, a general examination of the child by a pediatric endocrinologist, gynecologist and urologist should be carried out as early as possible. During examination, the genitals are evaluated – their size, position, structure and degree of development; the location of the opening of the urethra; the presence of a visible opening of the vagina, palpable testicles; the degree of fusion of labioscrotal folds. When diagnosing female pseudohermaphroditism, it is important not to miss the signs of congenital adrenal hyperplasia (the presence of areolar or genital hyperpigmentation, arterial hypertension or dehydration).
Until the end of diagnostic measures, the assignment of gender and name to the child is postponed, since the erroneous attribution of girls with female pseudohermaphroditism to the male sex can have very serious consequences. To detect female pseudohermaphroditism, a thorough study of the family history and the course of pregnancy, laboratory and instrumental diagnostics (repeated – up to 2 years of age) is carried out. If female pseudohermaphroditism is suspected, a cytogenetic study is performed (determination of the karyotype of leukocytes), determination of the level of electrolytes, pituitary hormones, adrenal glands and sex glands (LH, FSH, 17-ketosteroids, 17-hydroxyprogesterone, testosterone) in urine and blood serum.
Gynecology uses instrumental methods – pelvic ultrasound and X-ray contrast examination of the internal genitalia to visualize the vagina, cervix and uterine body. Histological examination of the tissue of the genital glands in the diagnosis is possible only in passing during the revision of the pelvic organs during any operation. When confirming the diagnosis of female pseudohermaphroditism, virilized girls are assigned female sex according to chromosomal and gonadal sex.
When diagnosing female pseudohermaphroditism with adrenogenital syndrome from the first day, it is necessary to monitor the water-electrolyte balance in order to prevent the possible development of a salt loss crisis. In the treatment of female pseudohermaphroditism, hormone replacement therapy with glucocorticoids and mineralocorticoids is prescribed as early as possible. Taking steroid hormones throughout the life of a patient with female pseudohermaphroditism prevents further virilization and promotes the proper development of the female body.
A child with female pseudohermaphroditism is performed intimate plastic surgery – reconstructive operations to restore the normal appearance of the genitals: at the age of 2 years – reduction clitoroplasty, in prepubertal – vaginoplasty. An important component of the treatment of female pseudohermaphroditism is psychological assistance to the child and his parents. Sometimes, with female pseudohermaphroditism, starting from puberty, additional intake of female sex hormones is necessary.
Adequate treatment of female pseudohermaphroditism contributes to the timely formation of menstrual function and the development of secondary sexual characteristics of the female type. In the future, girls born with a diagnosis of female pseudohermaphroditism, having normal ovaries, uterus and fallopian tubes, are capable of normal sexual function and pregnancy.
The prognosis depends on the severity of the disease, the timeliness and adequacy of treatment. The lack of treatment for female pseudohermaphroditism leads to the progression of virilization, the exclusion of the possibility of adequate puberty according to the female type, the course of normal menstrual function and childbirth. The severity of the symptoms of female pseudohermaphroditism, especially during puberty, can severely injure the psyche of a child.
With early and properly conducted treatment of female pseudohermaphroditism, cosmetic restoration of external genitalia, virilized girls can have full reproductive capabilities. Otherwise, women with pseudohermaphroditism may resort to assisted reproductive technologies: stimulation of superovulation, artificial insemination using the IMSI or ICSI method, IVF with a donor egg or a donor embryo, IVF under the surrogacy program.