Hypogonadism is a condition where the testicles do not function properly, which can affect sperm production and/or testosterone synthesis. Symptoms vary depending on the amount of missing testosterone and whether the condition develops before or after puberty.

Epidemiology and Causes

Male hypogonadism can be divided into three main categories:

● Primary Hypogonadism (Hypergonadotropic): Caused by a problem in the testicles.
● Secondary Hypogonadism (Hypogonadotropic): Caused by insufficient production of hormones that stimulate the testicles.
● Androgen Insensitivity: The body’s tissues do not respond to male hormones.

Here are some common conditions associated with these categories:

Primary Hypogonadism (Hypergonadotropic):
● Absence of testicles
● Undescended testicles
● Klinefelter Syndrome
● Genetic abnormalities
● Trauma, testicular torsion, infections
● Side effects of medical treatments (surgery, medications, radiotherapy)
● Exposure to toxins, heat, or occupational hazards
● Systemic diseases (liver cirrhosis, kidney failure)
● Testicular cancer
● Varicocele
● Unknown causes (e.g., late-onset hypogonadism)

Secondary Hypogonadism (Hypogonadotropic):
● Congenital

○ Idiopathic Hypogonadotropic Hypogonadism

○ Kallmann Syndrome

● Acquired (brain tumors)

○ Diencephalon, hypothalamus, pituitary

○ Empty Sella Syndrome

○ Granulomatous diseases

○ Brain injuries

○ Hyperprolactinemia

○ Medications / anabolic steroids, radiotherapy

Androgen Insensitivity:

● Testicular feminization
● Reifenstein Syndrome

In summary, hypogonadism is a complex issue with many potential causes, but the result is always a reduced production of hormones or sperm that can profoundly affect a person’s life.

Idiopathic Hypogonadotropic Hypogonadism: Etiology, Diagnosis, and Treatment
Idiopathic hypogonadotropic hypogonadism is a condition characterized by low levels of gonadotropins and sex steroids without anatomical or functional abnormalities of the hypothalamic-pituitary-gonadal axis. This type of hypogonadism can be isolated or associated with anosmia/Hyposmia (Kallmann Syndrome). Genetic factors affecting gonadotropin production can act at the hypothalamic or pituitary level, with specific mutations found in about 30% of congenital cases. These should be examined before considering assisted reproduction. Acquired hypogonadism can be caused by medications, anabolic steroids, or tumors.
To diagnose a possible tumor, CT or MRI of the sellar region and a complete endocrine screening are used. Androgen replacement therapy can help develop secondary sexual characteristics in patients who had hypogonadism before puberty. However, to stimulate spermatogenesis, treatments with human chorionic gonadotropin (hCG) along with recombinant FSH, highly purified urinary FSH, or menotropins (HMG) are required. If the hypogonadism is of hypothalamic origin, pulsatile GnRH therapy can be used. For patients who were not treated before puberty, one or two years of therapy may be needed to achieve sperm production.

Hypergonadotropic Hypogonadism: Etiology, Diagnosis, and Treatment
Hypergonadotropic hypogonadism occurs when the testicles are not functioning properly and can lead to high levels of FSH and/or LH. These conditions often affect only reproductive function, but in some cases, such as Klinefelter Syndrome, they can also affect testosterone production with aging. After extensive testicular biopsies, testosterone levels may decrease, requiring long-term endocrine follow-up.
The diagnosis of hypergonadotropic hypogonadism is based on high levels of FSH, low serum testosterone levels, and high LH levels. It is important to evaluate total testosterone considering the concentration of sex hormone-binding globulin (SHBG). Blood samples for testosterone should be collected before 10:00 a.m. due to diurnal variations.
Androgen replacement therapy is generally not recommended for men considering parenthood or in cases of male infertility, as testosterone can suppress the production of LH and FSH. In obese men, low testosterone levels may be due to conversion to estradiol by the enzyme aromatase. In these cases, anti-estrogens and aromatase inhibitors may help increase FSH and LH levels, improving sperm quality along with weight loss.