Male pseudohermaphroditism is a violation of the phenotypic sex, in which in persons with a normal male karyotype and testicles, the external genitals are formed according to the female type. Depending on the form of male pseudohermaphroditism, the external genitalia may have a female or intersex structure; the testicles remain underdeveloped to varying degrees; during puberty, male or female secondary sexual characteristics may develop to a greater extent. Examination of patients with male pseudohermaphroditism includes determination of karyotype, sexual chromatin, ultrasound, diagnostic laparoscopy, determination of hormone levels (testosterone, estradiol, LH, FSH, prolactin). Taking into account sexual orientation in male pseudohermaphroditism, appropriate correction of external genitalia, hormonal treatment, gonadectomy is carried out.
General information
Male pseudohermaphroditism (false male hermaphroditism) is a mismatch of the genital and gonadal sex in persons who are genetically male (karyotype 46, XY). Thus, in male pseudohermaphroditism, there is a violation of the differentiation of the external genitalia, while the sex glands of the individual correspond to the male sex. The prevalence of male pseudohermaphroditism is unknown, since the diagnosis of incomplete forms of the anomaly is difficult. The problems associated with true hermaphroditism, as well as male and female pseudohermaphroditism, are interdisciplinary, requiring a joint approach to their solution from andrology, gynecology, endocrinology, genetics.
Causes
The origin of male pseudohermaphroditism may be associated either with defects in the synthesis and metabolism of androgens, or with a violation of their action on target tissues. All these factors act even in embryogenesis, during sexual differentiation. Defects in androgen biosynthesis can occur with insufficiency of enzyme systems that provide a complex multi-stage process of testosterone formation from cholesterol. Enzyme deficiency leading to steroidogenesis disorder may be associated with a deficiency of cholesterol-desmolase, Pp-hydroxysteroid dehydrogenase, 17a-hydroxylase, 17-oxidoreductase, 17a-ketosteroid reductase, 17,20-desmolase. In addition to the biochemical pathway, a violation of androgen synthesis can be caused by aplasia of Leydig cells caused by genetic mutations of luteinizing hormone or LH receptors. Androgen synthesis defects are inherited by autosomal recessive type.
Some forms of male pseudohermaphroditism are caused by a violation of the action of androgens and a change in the sensitivity of tissues to testosterone. In this case, the synthesis of testosterone is not changed, but the target cells turn out to be resistant to its action, which is accompanied by a violation of the development of the individual according to the male type to one degree or another. The basis of the violation of the action of androgens may be insufficiency of 5a-reductase (autosomal recessive type of male pseudohermaphroditism) or pathology of androgen receptors (X-linked recessive type of male pseudohermaphroditism). A rare variant of male pseudohermaphroditism is the Muller duct persistence syndrome. It is assumed that this form is due to violations of the synthesis or action of the anti-Muller hormone at the stage of sexual differentiation of the fetus. In general, much remains unclear about the etiology and pathogenesis of male pseudohermaphroditism.
Symptoms
The variety of causes of male pseudohermaphroditism determines the polymorphism of the clinical picture. So, with the insufficiency of the enzyme systems involved in the synthesis of testosterone, hypospadias, micropenis, underdevelopment of the scrotum may occur. Testicles can be located both in the scrotum and outside it; incomplete masculinization takes place. In extreme forms of enzyme deficiency, the external genitalia of a boy can be fully formed according to the female type.
Male pseudohermaphroditism caused by 5a-reductase deficiency is characterized by perineal-scrotal hypospadias and the presence of a blindly ending vagina. At the same time, patients have well-developed testicles, appendages, vas deferens and seminal vesicles. Gynecomastia does not develop, axillary and pubic hair loss occurs according to the male type. The level of testosterone in the blood plasma is normal.
In the pathology of androgen receptors, several different phenotypic variants of male pseudohermaphroditism can be formed. The most common diagnosis in this group is complete testicular feminization, occurring in 1:20000-1:64000 newborn boys. With this form of male pseudohermaphroditism, patients phenotypically look like women: the external genitals are formed according to the female type; there is a rudimentary or short, blindly ending vagina. The physique is peculiar to female persons; the mammary glands are sufficiently developed, however, there is an absence or weak severity of axillary and pubic hair. Usually, the diagnosis of male pseudohermaphroditism is established in connection with a visit to a doctor about an inguinal hernia, primary amenorrhea or infertility. This reveals the absence of female internal genitalia, the presence of testicles (in the abdominal cavity, inguinal canals or folds of the labia majora). Patients with complete testicular feminization psychosexually identify themselves as women.
A rarer form of male pseudohermaphroditism is incomplete testicular feminization, which occurs 10 times less often than the full form. In this case, there is virilization of the external genitals (hypertrophy of the clitoris, scrotum-like labia majora), the presence of hair on the upper lip, undeveloped mammary glands, etc. Patients have a blindly ending short vagina, testicles with underdeveloped appendages.
Reifenstein syndrome, as a form of male pseudohermaphroditism, can have various manifestations. Most often, patients are diagnosed with perineal-scrotal hypospadias, gynecomastia, cryptorchidism, testicular hypoplasia, azoospermia, male infertility. The degree of facial and chest hair is expressed minimally. In most cases, such patients feel like men, so they need surgical correction of hypospadias, testicular reduction, surgical elimination of gynecomastia.
One of the rarest forms of male pseudohermaphroditism is the Muller duct persistence syndrome (no more than 100 cases have been described). Clinical signs include the presence of a vaginal process, uterus and fallopian tubes in males. Patients have a normally developed penis and secondary male sexual characteristics, but they often encounter cryptorchidism, inguinal hernias, testicular tumors.
Diagnostics
If a patient has abnormalities of the external genitals, in order to exclude or confirm the diagnosis of male pseudohermaphroditism, he should be examined as early as possible by an endocrinologist, gynecologist, urologist, geneticist. During the general examination, the structure of the genitals is assessed: their size and degree of development, the location of the external opening of the urethra, the presence of palpable testicles and visible entrance to the vagina, etc.
With the help of ultrasound examination (ultrasound of the pelvic organs, abdominal cavity, inguinal canals), it is possible to detect the presence or absence of female genitals, as well as to detect testicles. Examination of patients with suspected male pseudohermaphroditism is supplemented by hormonal studies – determination of testosterone, estradiol, LH, FSH, prolactin levels. The dynamics of changes in the level of sex hormones is assessed using a functional test with HCG. To clarify the anatomical diagnosis, diagnostic laparoscopy or laparotomy with a biopsy of the genital glands is performed. All patients with suspected male hermaphroditism are examined for karyotype and determination of sexual chromatin.
In most cases, testicular feminization is detected during puberty and post-puberty, when phenotypic girls and women turn to a gynecologist with complaints about the absence of menstruation, the inability to lead a normal sexual life or infertility. In children, pathology can be diagnosed during herniation, in the case when a testicle is found in the inguinal canal.
Treatment
The main criteria determining the tactics of treatment of male pseudohermaphroditism and the choice of a civil gender are the sexual autoidentification of the patient and the clinical picture of pathology. Patients with false pseudohermaphroditism, having male external genitalia and psychosexual orientation, are prescribed testosterone treatment. If necessary, they perform the reduction of the testicle, elimination of gynecomastia surgically, correction of hypospadias, elongation of the penis.
Patients with testicular feminization syndrome are shown to have ectopic testicles removed (in full form – after puberty, with incomplete form – at prepubescent age). After surgery, estrogen replacement therapy is prescribed to maintain feminization. If the size of the vagina is insufficient, preventing the conduct of a normal sexual life, vaginoplasty or colpoelongation is performed. In the presence of clitoromegaly, the clitoris is corrected.
Social adaptation and rehabilitation of patients with male pseudohermaphroditism depends on the timing of pathology diagnosis, assignment of the most appropriate civil gender and appropriate correction of phenotypic signs, the correctness of upbringing in the family. With the successful solution of these tasks, patients are capable of leading a sexual life and creating a family. The fertility prognosis is doubtful in most cases.
