Disorders of Sexual Development: An Overview of Information

Sex is a complex concept, consisting of several interrelated links in the reproductive system: the genetic structure of the sex cell (genetic floor), gonadal morphology (gonadal sex), the balance of sex hormones (hormonal sex), sex organs and secondary sexual characteristics (somatic sex), psychosocial and psychosexual self-determination (mental sex), a certain role in the family and society (social sex). In the end, sex is a biologically and socially conditioned role of the subject in the family and society.

The formation of a person's sex takes place in ontogenesis in several stages.

• I stage. The sex of the future organism is predetermined at the time of fertilization and depends on the combination in the zygote of the sex chromosomes: the XX set corresponds to the female, the XY corresponds to the male sex. The activity of the activator gene of HY genes, which determine the development of the primary gonad in the male direction, is associated with the Y-chromosome. They trigger the synthesis of HY-antigen and protein-receptors to it, the genes of which are localized in other chromosomes. Another system of Y chromosome genes provides development of the epididymis, seminal vesicles, the vas deferens, the prostate gland, the external genitalia in the male direction, and the involution of the Müller derivatives.
• In the germ cells of the primary gonad (with both XY and XX chromosome sets), there are receptors to the HY antigen, while in somatic cells they are present only in the XY-set, the structure of somatic receptors for HY antigen includes a special type of beta- microglobulin, whereas the receptors of germ cells to the HY antigen (and XY, and XX) are not associated with this specific protein. This probably explains the bipotentiality of the primary gonad.
• II stage. Between the 7th and 10th week of intrauterine development, the sex glands are formed in accordance with the set of sex chromosomes.
• Stage III. Between the 10th and 12th week of embryogenesis, internal genitalia are formed. Functionally high-grade testicles during this period secrete a special peptide hormone, which causes resorption of Muller's derivatives. In the absence of testicles or in their pathology, the internal female genital organs (uterus, tubes, vagina) develop even in the embryo with the genetic male sex (46.XY), in violation of the production of anti-Muller hormone.
• IV stage. Between the 12th and 20th week of embryogenesis, external genitalia form. The determining role in men's development at this stage is played by androgens (regardless of their source) - testicular, adrenal, coming from the mother's body (if the mother has androgen-producing tumors or in connection with taking androgenic drugs). In the absence of androgens and in violation of the receptor sensitivity to them, external genitalia are formed according to the female ("neutral") type even in the presence of 46, XY karyotype and normal function of embryonic testicles. It is also possible to develop intermediate variants (incomplete masculinization).
• V stage. Lowering testicles into the scrotum. It occurs between the 20th and the 30th week of embryogenesis. The mechanism that causes or disrupts the progress of the testicles is not fully understood. However, there is no doubt that both testosterone and gonadotropins are involved in this process.
• The sixth stage of sexual differentiation occurs already at the age of puberty, when the connections in the hypothalamus-pituitary-gonad system are finally formed, the hormonal and generative function of the gonads is activated and the social-sexual identity determining the role of the subject in the family and society is consolidated.

Causes and pathogenesis of sexual development disorders. According to etiology and pathogenesis, congenital forms of sexual development disorders can be divided into gonadal, extragonadal and extraphetal; among the first two, a large proportion accounted for genetic pathology. The main genetic factors of the etiology of the forms of the congenital pathology of sexual development are the absence of sex chromosomes, an excess of their number or their morphological defects that can arise as a result of meiotic division of chromosomes (oogenesis and spermiogenesis) in the parents' body or in the defect of dividing the fertilized ovum (zygote) stages of crushing. In the latter case, there are "mosaic" variants of chromosomal pathology. In some patients, genetic defects manifest themselves as autosomal gene mutations and are not recognized by light microscopy of chromosomes. With gonadal forms, the morphogenesis of the gonad is impaired, which is accompanied by both the pathology of the antimulylerovoy activity of the testicles, and the hormonal (androgenic or estrogenic) function of the gonad.

Causes and pathogenesis of sexual dysfunction

Clinical characteristics of the main forms of congenital pathology of sexual development

In distinguishing the clinical form as a specific nosological unit, it should always be borne in mind that between the types of pathology closely located on the scale of stages of embryogenesis, intermediate types can exist, in separate features bearing the signs of neighboring forms.

Main clinical signs of congenital pathology.

1. Pathology of gonad formation: complete or unilateral absence, violation of their differentiation, the presence of one individual gonadal structures of both sexes, degenerative changes in gonads, non-admission testicles.
2. Pathology of the formation of internal genitalia: the simultaneous presence of derivatives of Muller and volphic passages, the absence of internal genitalia, inconsistency of the gonad floor with the structure of internal genitalia.
3. Pathology of the formation of external genitalia: a mismatch of their structure with the genetic and gonadal sex, sexually defined structure or underdevelopment of the external genitalia.
4. Violation of the development of secondary sexual characteristics: the development of secondary sexual characteristics that do not correspond to the genetic, gonadal or civil sex, absence, insufficiency or premature development of secondary sexual characteristics, absence or delay of menarche.

Symptoms of sexual dysfunction

Diagnosis of various forms of congenital pathology of sexual development

The main principle of diagnostic research in the congenital pathology of sexual development is to elucidate the anatomical and functional state of all links that make up the concept of sex.

Inspection of the genitals. When a child is born in the definition of sex, the doctor is guided by the structure of the external genitalia ("obstetric floor"). With gonad agenesis and the full form of testicular feminization, the structure of the external genitalia is always feminine, so the issue of electing a female civic gender is decided unequivocally, despite the genetic and gonadal sex, which in the latter case will be masculine. In the syndrome of testicular feminization, the diagnosis in a number of cases can be established at the age of adulthood in the presence of testicles in "large lips" or inguinal hernias. Palpation of extra-abdominal testicles allows to determine their size, consistency, and suggest the possibility of tumor changes.

With abdominal cryptorchidism in boys and severe forms of congenital dysfunction of the adrenal cortex in children with a female genetic and gonadal sex, the structure of the penis may be normal, which often leads to an erroneous evaluation of the newborn girl as a boy with cryptorchidism. With Klinefelter's syndrome, the structure of the external genitalia at birth is normal male, which does not allow diagnosis on the basis of a routine examination.

Diagnosis of sexual dysfunction

Treatment of the congenital pathology of sexual development consists of several aspects. The main issue is the establishment of the patient's gender, adequate to his biological and functional data, taking into account the prognosis of the possibility of sexual activity.

If the corresponding sex of the underdeveloped genitalia, the absence or surgical removal of the gonads, as well as in case of growth disorders, hormonal correction of development is necessary, forming a phenotype approaching the norm and providing a normal level of sex hormones.

Surgical correction of the floor involves the formation of external genitalia depending on the sex chosen (feminizing or masculinizing reconstruction), as well as addressing the fate of gonads (their removal, removal from the abdominal cavity, or the descent of testicles into the scrotum). When choosing a male patient with dysgenesis of testicles, removal of the rudimentary uterus is not necessary from our point of view, since in the future its presence does not give any complications. Some patients with the syndrome of incomplete masculinization and testicular feminization need to create an artificial vagina.

Treatment of sexual dysfunction