Hypogonadism: Causes, Symptoms, Diagnosis, and Treatment Methods

Hypogonadism is a pathological condition caused by a deficiency of male sex hormones, characterized by underdevelopment of sexual organs and secondary sexual characteristics.

Causes of Hypogonadism

Primary congenital hypogonadism typically results from a genetic defect of hereditary nature or arising during embryonic development:

•   Inheritance of 3 or more chromosomes instead of a pair (Klinefelter syndrome);
•   Inheritance of only one X chromosome instead of a pair (Turner syndrome);
•   Formation of testicular epithelium atrophy (Del Castillo syndrome).

Hypogonadism is frequently detected in patients with anorchism (absence of testicles), monorchism (absence of one testicle), cryptorchidism (undescended testicle/s), or abnormalities in the seminiferous tubules.

The fetal reproductive system may suffer due to adverse effects on the pregnant woman’s body (X-rays, radiation therapy, hormonal medications, pregnancy toxemia, toxic substances).
The risk of hypogonadism increases in patients who have previously had mumps, syphilis, orchitis, and some other infectious diseases.
Acquired primary hypogonadism may develop as a result of varicocele, early castration, testicular torsion, or tumors of the reproductive glands.
Secondary congenital hypogonadism may manifest in the context of Kallmann syndrome (hypothalamic deficiency) or Maddock syndrome (hypopituitarism).
Secondary acquired hypogonadism develops due to central nervous system disorders: pituitary adenomas, pituitary surgeries, pituitary tumors leading to excess prolactin production, encephalitis, meningitis, excessive iron accumulation in tissues, as well as opioid and corticosteroid use.

Disease Classification

According to the etiological principle, hypogonadism is classified as:

•   Primary (hypergonadotropic),
•   Secondary (hypogonadotropic),
•   Mixed,
•   Caused by disruption of the negative feedback loop "hypothalamus-pituitary-gonads."

The course of hypogonadism is determined by several factors:

•   The source of the pathology;
•   Which glands are involved in the process;
•   At what stage of development the disease manifested.

By age, prepubertal (before 12 years old) and postpubertal forms of hypogonadism are distinguished.

Based on the frequency of symptom manifestation, hypogonadism can be chronic or transient.

Symptoms of Hypogonadism

The symptoms of hypogonadism vary significantly depending on the factors that contributed to the development of the pathology, which glands are involved in the pathological process, at what stage of organism development the first signs of the disease were detected, and the degree of their expression.

Congenital primary hypogonadism manifests most prominently.
Disorders occurring before the 20th week of embryonic development lead to underdevelopment of sexual organs, hermaphroditism, cryptorchidism, complex growth and developmental defects.

With secondary hypogonadism, disturbances in the function of organs and systems related to the pituitary gland are observed: endocrine, nervous, and reproductive. As a result, hypogonadism can manifest as abnormally high growth, excessive weight, infertility, hexadactyly, delayed physical development, laryngeal hypoplasia, facial and body asymmetry, decreased or complete absence of smell, adrenal insufficiency, decreased mental abilities.

Hypogonadism acquired in adulthood does not affect physical development but has a number of characteristic signs associated with metabolic, psychological, and reproductive disorders. Patients with this form of the disease typically exhibit paleness and thinning of the skin, episodes of insomnia, rapid fatigue, memory impairment, depressive states, breast enlargement, decreased bone mass, fluctuations in blood pressure, reduced size of the prostate gland and sexual organs, formation of fat deposits in a female pattern, and erectile dysfunction.

Diagnosis of Hypogonadism

Male hypogonadism can often be diagnosed during a medical examination. According to the diagnostic protocol, the doctor measures the patient’s height, body proportions (limb length, upper segment, arm span), assesses the degree of development of subcutaneous adipose tissue and muscle mass, and observes the distribution of fat tissue.

Pubertal development in boys is assessed using the Tanner scale.
Physical examination also includes an examination of the patient’s external genitalia for any abnormal penile structure, evaluation of the state, size, and position of the testicles relative to the scrotum: testicular volume is measured using a Prader orchidometer.

Laboratory tests are prescribed to determine the current condition of the patient:

•   Testosterone level;
•   Luteinizing hormone level;
•   Follicle-stimulating hormone level;
•   Prolactin level;
•   Estradiol level;
•   Thyrotropin level;
•   Sex hormone-binding globulin level;
•   Adrenal androgen activity test;
•   X-ray for determining bone age;
•   Ultrasound of the prostate gland and scrotum;
•   CT or MRI of the brain (for secondary form of the pathology).
•   Semen analysis - to determine the quantity and quality of ejaculate.
Treatment of Hypogonadism

Only after establishing an accurate picture of the disease and identifying the cause that contributed to the development of the pathology, individual treatment is prescribed.
In cases of male sex hormone deficiency, testosterone levels are normalized using hormone therapy. Treatment typically consists of two stages: hormonal replacement therapy with testosterone-containing medications and stimulating therapy aimed at activating the production of endogenous testosterone.
The decision on the application of a particular methodology, duration of the course, and dosages is made by the attending physician, taking into account the specific characteristics of the patient’s disease progression.
Secondary hypogonadism in men is treated by addressing the underlying condition that led to the pathology. Such patients do not require additional administration of sex hormones.

Without treatment, hypogonadism can lead to infertility, psychological problems, endocrine disorders, osteoporosis, and bone fragility. Visible complications may include disproportionate body shape, gynecomastia, and atrophy of the sexual organs.

Prevention of Hypogonadism

If there is a history of hypogonadism in the family, it is advisable to consult a geneticist when planning pregnancy.

During pregnancy, women should avoid taking nonsteroidal anti-inflammatory drugs (it has been shown that they increase the risk of giving birth to a child with cryptorchidism).

Boys should be vaccinated against mumps in a timely manner, considering the complications that this disease can cause.