Men's Health Knowledge: Analysis of Congenital Developmental Abnormalities of the Reproductive System and Intervention Methods

Congenital Malformations of the Reproductive System

Because early embryos have the potential to develop into either male or female, abnormalities in sex development can lead to various degrees and types of sex deformities. Embryonic sex differentiation depends on sex hormones, and the differentiation of embryonic gonads is controlled by sex chromosomes. However, only the genetic code entering the chromosomes can express itself normally. During early embryonic development, it may be affected and interfered with by various factors that lead to malformations, causing the embryo to develop in an abnormal direction. For example, some studies have exposed fish larvae to high concentrations of sex hormones, completely reversing the direction of the fish's sex genetic code. Exposing XY larvae to estrogen caused larvae destined to become male to become female, and surprisingly, this XY female fish was able to reproduce with XY male fish. The second-generation juvenile fish have a chromosome distribution of 25% XX (female), 50% XY (male), and 25% YY (male). Exposing the YY juveniles to estrogen will allow them to develop into YY females. The third generation may be bred using YY males and females, resulting in entirely YY fish. Without special treatment, these YY fish will all develop into males. Treating XX female juveniles with male hormones using the same experimental method can cultivate XX males. In human fetal development, a lack of male hormones will cause male fetuses to develop towards female external characteristics. Insufficient male hormone secretion will result in incomplete male fetal development, such as a short penis and incomplete testicular descent. Conversely, excessive male hormones can cause XX female fetuses to develop towards male external characteristics, resulting in sex deformities. Hermaphroditism is classified into true hermaphroditism and pseudohermaphroditism based on the histological structure of the gonads. True hermaphroditism involves the presence of both male and female gonads, meaning both testes and ovaries are present in a single individual. Pseudohermaphroditism involves only one gonad, either testes or ovaries.

(I) Male Pseudohermaphroditism

These patients have a 46XY karyotype and occur in approximately 1/20,000-64,000 of all newborn male infants. Their personality traits, breast development during puberty, genital appearance, and overall body fat distribution are all female-like. The external genitalia are often a blind-ended vagina. The testes are hidden in the abdominal cavity, groin, or labia majora. Sometimes, the patient's androgen levels may be normal, but normal male differentiation may not be observed. The main reasons for this condition are as follows: 1. During the embryonic reproductive organ development stage (10-12 weeks), insufficient androgen secretion causes the normal differentiation of male external genitalia to stop, and the genital tubercle fails to form a normal penis. At this time, under the influence of estrogen, differentiation begins to develop towards female characteristics, resulting in the appearance of female genitalia. Androgen deficiency is related to congenital gonadal dysgenesis, impaired testosterone synthesis, and insensitivity of testicular interstitial cells to gonadotropins.

(II) Female pseudohermaphroditism

Patients have normal ovaries and internal reproductive tracts, but their external genitalia exhibit hermaphroditism. The clitoris is enlarged, resembling a male penis, and the labia are merged, resembling a scrotum. After birth, they are often mistaken for boys. Their karyotype is 46XX. This abnormal developmental state is mainly caused by excessive androgen influence during the reproductive organ development stage. Congenital adrenal hyperplasia in the fetus, leading to excessive androgen production, or high levels of androgens in the mother during pregnancy, can both cause abnormal development of the reproductive organs. Maternal intake of exogenous testosterone and natural or synthetic progestins before 12 weeks of gestation can cause masculinization in female fetuses. Norethindrone, ethinylestradiol, and medroxyprogesterone acetate can also cause masculinization in female fetuses. In a few cases, ovarian or adrenal cortex tumors in pregnant women secrete excessive androgens, resulting in a relative deficiency of estrogen, which is also a factor in fetal masculinization.

(III) True Hermaphroditism

These patients possess both male and female gonads, namely the testes and ovaries. The differentiation of the internal and external genitalia is highly differentiated; the external genitalia may be male or female, but it is mostly hermaphroditism. Cryptorchidism and hypospadias are common, and all cases have a uterus. If left untreated before puberty, most patients will develop breasts, and about 50% will menstruate. Ovarian function is normal, but testicular development and function are often abnormal. The sex chromosome karyotype is 46,XX in 60% of cases, 46,XY in 20%, and mosaicism (XXY or XX,XY) in 20%. About one-third of patients have an ovary on one side and a testis on the other; 20% have a mixture of testicular and ovarian tissue on both sides, called an ovotestis. A common characteristic of these patients is the presence of both ovarian and testicular tissue within the same individual. The ovaries are generally in their normal position, while the testes can be located in the groin, scrotum, or abdominal cavity. Normally, these testicular tissues have atrophied, leaving only a transparent spermatic cord.

(IV) Cryptorchidism

Cryptorchidism refers to testes not located in the normal scrotum, including incomplete testicular descent and ectopic testes. The former refers to the testis remaining at any point along its descent path, such as in the inguinal canal, internal inguinal ring, below the external inguinal ring, or within the abdominal cavity. The latter refers to the testis being located anywhere outside the descent pathway, such as subcutaneous inguinal region or perineum.

1. Causes and Adverse Consequences of Cryptorchidism

In early embryonic development, the testis is located in the retroperitoneal space below the diaphragm and gradually descends as the embryo develops. By 4-6 months of embryonic development, the testis is close to the internal inguinal ring, and by 7-9 months, it descends into the scrotum. Some testes are not yet in the scrotum at birth but descend spontaneously several months later. Due to slow testicular descent and restricted closure of the processus vaginalis, indirect inguinal hernia is easily formed. Therefore, incomplete testicular descent is often accompanied by indirect inguinal hernia. Testicular descent is accomplished by the action of gonadotropins and the traction of the gubernaculum testis. Therefore, insufficient gonadotropin secretion or underdeveloped testicular tissue is insensitive to sex hormones, which is the endocrine cause of cryptorchidism. Cryptorchidism caused by this factor is mostly bilateral. Abnormalities in the anatomical tissues during testicular descent or abnormal termination of the gubernaculum testis can also lead to cryptorchidism. For example, underdeveloped inguinal canal or a short spermatic cord can cause unilateral incomplete testicular descent, and abnormal termination of the gubernaculum testis can often result in ectopic testes. Some statistics show that cryptorchidism accounts for 9.2%–30% in immature infants and 4.5%–5.8% in mature infants. In a statistical study of 88,562 patients, cryptorchidism occurred in 1.82% of children over 1 year old; in another group of 3,612 children, 28 cases (0.8%) had cryptorchidism over 1 year old. Both groups of patients with cryptorchidism showed no significant change by puberty, indicating that the chance of spontaneous testicular descent after 1 year of age is low. The adverse consequences of cryptorchidism on the human body mainly include the following:

① Testicular atrophy and loss of spermatogenesis. This is due to the long-term high temperature in and around the abdominal cavity. The optimal temperature for testicular tissue survival is slightly lower than the normal abdominal temperature; above this range, the survival of testicular tissue cells is affected.

② Malignant transformation. This is because testicular tissue cells, exposed to a high-temperature environment for a long time, are prone to malignant transformation and tumor formation. The incidence of tumors in cryptorchidism is dozens of times higher than in normal individuals.

③ Susceptibility to compression and injury.

④ Increased risk of psychological distress.

2. Clinical Treatment of Cryptorchidism

① Endocrine therapy: Generally, gonadotropin therapy is recommended before the age of 6.

② Surgical repositioning: If endocrine therapy is ineffective, surgical repositioning should be performed promptly.

③ For some post-pubertal or adult patients with cryptorchidism, the abnormally positioned testicular tissue should be removed promptly to prevent malignant transformation.

(V) Hypospadias

Hypospadias is the most common type of urethral malformation. It mainly results from the incomplete fusion of the urethral folds on both sides of the urethral groove during the embryonic period, causing a defect in the distal urethra. This defect is often replaced by connective tissue or fibrous strands. Besides urethral defects, this pathological change can also cause penile deformities, such as dorsal penile curvature that cannot be straightened, or excessive foreskin accumulation on the dorsal side forming an eagle-cap deformity. Hypospadias is classified into glans type, frenulum type, penile type, scrotal type, and perineal type, etc. Severe hypospadias patients are unable to urinate upright.

This congenital malformation generally has no impact on the child except for their parents. Although the urethral opening is abnormal, it is rarely narrowed, therefore it does not affect urine output. However, by the time they reach kindergarten age, they are often teased by their peers for not being able to urinate upright, leading to feelings of inferiority and abnormal psychological states. Even after marriage, the inability to achieve normal penile erection can affect sexual life and, of course, fertility.

Patients with hypospadias should seek medical treatment before school age. The goal of treatment is clear: to reconstruct and repair the damaged urethra and correct penile lateral flexion deformity, restoring penile erection and normal upright urination and sexual function.