15th April 2024

Male hypogonadism

Hypogonadism can be broadly classified into two types; pathological hypogonadism and late-onset hypogonadism.

Primary hypogonadism

There are various causes of primary hypogonadism, the clinical presentation of primary hypogonadism is dependent on when the insulting stimulus occurs.

Congenital causes:

• Klinefelters syndrome
• Cryptorchidism
• Myotonic dystrophy
• LH receptor mutations

Acquired causes:

• Orchitis (mumps, chlamydia)
• Testicular torsion/trauma
• Chemotherapy
• Iatrogenic/Drug induced (Spironolactone, Alcohol, anabolic steroid use, ketoconazole)
• Bilateral orchiectomy

Prenatal hypogonadism

Prenatal hypogonadism occurs due to insufficient testosterone levels during the first three months of foetal development. In a foetus with a normal karyotype, this is associated with disorders of sexual differentiation with the severity dependent on the level of testosterone reduction, ranging from a complete lack of male genital organs to scrotal abnormalities and under masculinisation (ectopic urethral meatus/micropenis).

Prepubertal hypogonadism

If the insult occurs before puberty, the patient will present with characteristic phenotypical features, including a high-pitched voice, ‘eunuchoid proportions’, gynecomastia, increased fat deposition and decreased muscle mass. These patients may also have reduced libido, erections and an inability to ejaculate.

Post pubertal hypogonadism

If the insult occurs after puberty, the clinical presentation depends on the severity and duration of low testosterone levels. These patients may present with a wide range of symptoms, including decreased lean body mass, increased fat deposition, hot flushes, insomnia, low energy levels and decreased bone mineral mass. As puberty has already occurred, the patient’s primary and secondary sexual features do not significantly change.

Central hypogonadism

There are various causes of central hypogonadism. Central hypogonadism can occur secondary to a disease process affecting the hypothalamus or pituitary gland or it may be inherited due to a mutation in particular genes such as those controlling the GnRH pathway (isolated hypogonadotropic hypogonadism /IIH) or genes related to migration of olfactory/GnRH secreting neurones during embryonic development (associated with Kallmann syndrome).

Central hypogonadism can occur in patients with damage to gonadotrophic cells due to compression (pituitary tumours, meningioma, craniopharyngioma), infiltrative disease (sarcoidosis, lymphoma) infections (Tuberculosis, syphilis) or infarction. Furthermore, the use of exogenous androgenous steroids leads to suppression of GnRH cell activity leading to central hypogonadism.