True hermaphroditism is a congenital disorder of sexual differentiation characterized by the presence of two types of gonads in an individual (ovary and testicle) or gonads of mixed structure (ovotestis). Clinical manifestations can be different and depend on the predominance of the functional activity of the male or female gonad. Patients with this disease may have a violation of the structure of the external genitalia (small penis, hypospadias, cryptorchidism, hypertrophy of the clitoris), gynecomastia, bisexual figure type; menstruation, ovulation and spermatogenesis are possible. The diagnosis is established on the basis of examination of the genitals, ultrasound of the gonads, examination of the level of sex hormones, clarification of the karyotype and biopsy of the gonads. Therapeutic tactics are determined by the psychosexual orientation of patients and consist in the removal of gonads of the opposite sex, hormone therapy.
Meaning
True hermaphroditism (intersexism, bisexual gonad syndrome) is a genetically determined disorder of sexual development in which the sex glands are represented by functioning elements of the ovaries and testicles. With true hermaphroditism, the ovaries and testicles can be located separately or be combined into a mixed sex gland – ovotestis. Pathology is an extremely rare phenomenon; in total, about 200 such cases have been described in the world medical literature. Much more common in gynecology and andrology is false hermaphroditism (male and female pseudohermaphroditism), characterized by the presence of an individual’s external genitalia of the same sex, and the sex glands of the opposite sex.
Classification
Among the cases of true hermaphroditism, there are variants when an individual has an ovary on one side and a testicle on the other; ovotestis is determined on both sides – a mixed gland with testicular and ovarian tissue; there is a unilateral ovotestis with a testicle or ovary on the other side. Sometimes, in the presence of ovotestis on one side, gonadal tissue on the opposite side is absent.
True hermaphroditism can be combined with abnormalities of the external genitalia or occur with normally formed external genitalia. Possible morphological forms of true hermaphroditism without anomalies of the external genitalia include:
- with a predominance of male secondary sexual characteristics
- with a predominance of female secondary sexual characteristics
- with equally pronounced secondary sexual characteristics of both sexes
- with genitals of the same sex and gonads of the opposite sex, contributing to manifestations of transsexualism.
True hermaphroditism with abnormalities of the external genitalia occurs in the following variants:
- with a full set of genitalia of one sex and the presence of one or more organs of the other sex
- with an incomplete set of genitalia of both sexes
- with a full set of genitalia of the male and female sexes.
Causes
The factors contributing to the emergence of true hermaphroditism have not been fully disclosed. The identification of family cases of violation indicates a possible hereditary conditionality of true hermaphroditism.
Approximately in 60% of cases of true hermaphroditism in patients, the female karyotype 46,XX is determined, in 10% of cases – the male karyotype 46,XY, in the rest there is a different kind of chromosomal mosaicism (46XX/46XY, 46XX/47XXY, etc.). It is assumed that cases of true hermaphroditism may be associated with translocation, non-divergence or mutation of chromosomes, as well as chimerism – double fertilization of the same egg, leading to the formation of bisexual gonads. The influence of extra-gonadal damaging factors causing simultaneous differentiation of the elements of the ovary and testicles is not excluded.
Symptoms
Clinical manifestations of true hermaphroditism are extremely diverse and can be detected in various variants and combinations. At birth, in 90% of children with true hermaphroditism, the external genitals have an intersex (mixed) structure and only 10% have definitely male or female signs. Among the anomalies of the external genitalia in persons with a male phenotype with true hermaphroditism, there are usually a micropenis, cryptorchidism, hypospadias; in persons with a female phenotype, clitoral hypertrophy, urogenital sinus.
The testicle may be located in the scrotum, labial fold, inguinal canal, abdominal cavity; the seminal tubules are atrophied in most cases, in rare cases there is preserved spermatogenesis. In the absence of gonads, the labial folds resemble large labia. Anomalies in the development of other organs are usually not characteristic of true hermaphroditism; sometimes pathology is combined with inguinal hernia.
On the side of the testicle, an appendage and a vas deferens are usually formed; on the opposite side, a one-horned uterus and a fallopian tube develop. The vagina can be well developed and open in the perineum, along the midline of the scrotum or into the posterior urethra. As a rule, the ovaries are located correctly; ovulation occurs in 25% of patients with true hermaphroditism.
During puberty, signs of virilization or feminization may be noted; secondary sexual characteristics of both sexes are often present (bisexual figure type, gynecomastia, low voice timbre, male-type hair loss). Half of the patients have menstruation; with the male phenotype, monthly bleeding is manifested by cyclic hematuria. Patients with true hermaphroditism may have problems with sexual identity and social adaptation; a tendency to bisexuality, homosexuality, transsexuality, transvestism.
Diagnostics
In order to confirm or exclude the diagnosis of true hermaphroditism, patients should be consulted by an endocrinologist, urologist, gynecologist, geneticist. Physical examination evaluates the development of external genitalia, the severity of secondary sexual characteristics. Palpation of the scrotum area, vaginal or rectal examination, ultrasound of the pelvic organs and adrenal glands are performed.
True hermaphroditism must be differentiated from false hermaphroditism, gonadal dysgenesis (Klinefelter syndrome, Shereshevsky-Turner syndrome). For this purpose, the determination of sexual chromatin, karyotyping, the study of the level of hormones (testosterone, estrogen, FSH, 17-ketosteroids in daily urine), other tests and samples are performed. The final diagnosis of true hermaphroditism can be established only after diagnostic laparotomy, gonad biopsy and histological confirmation of the presence of both ovarian and testicular tissue.
Treatment
The issue of assigning a passport gender and the nature of gender education of persons with true hermaphroditism is complex; it requires taking into account the karyotype, hormonal status, psychosexual orientation of the patient’s personality and is solved with the involvement of medical specialists. In most cases, newborns with true hermaphroditism are classified as female and brought up as girls, since the activity of the ovarian part of the gonad usually prevails over the testicular.
In the future, taking into account anatomical, psychological and functional aspects, surgical correction of true hermaphroditism is carried out, providing for gonadectomy and plastic surgery on the external genitalia. In persons with a female passport, the removal of all testicular tissue or ovotesis, resection of the clitoris, vaginal plastic surgery is performed. The problem of excessive hair loss is solved with the help of epilation methods. In the future, throughout the reproductive age, cyclic administration of estrogen-progestogenic drugs is prescribed. When choosing a male passport sex, patients with true hermaphroditism are completely removed from ovarian tissue and female genitalia, gynecomastia is corrected, scrotum formation, penile plastic surgery is performed. From puberty, replacement (supportive, stimulating) therapy with androgens is carried out.
Forecast
The normal psychosexual development and adaptation of patients with true hermaphroditism in society depends on the correctness of the choice of gender, the correspondence of the phenotype of the chosen gender and self-identification. Usually, patients with true hermaphroditism are infertile, however, individual cases have been described when individuals with a female and male phenotype, after removing the ovotestis or gonads of the opposite sex, were able to procreate.
Patients with true hermaphroditism, even after gonadectomy, should remain under the close supervision of an endocrinologist to monitor the correctness of hormone therapy. In some cases, such patients need the help of a psychologist, psychotherapist, sexologist.