Also Known As
Testosterone deficiency, Androgen deficiency, Male gonadal insufficiency, Testicular failure (primarily for primary hypogonadism), Hypoandrogenism, Low T.
Definition
Male hypogonadism is a clinical condition characterized by the failure of the testes to produce adequate levels of the male sex hormone, testosterone, and/or to produce normal numbers of sperm.¹ It results from a disruption at any level of the hypothalamic-pituitary-gonadal (HPG) axis, which regulates testicular function.² The hypothalamus produces gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH, in turn, stimulates the Leydig cells in the testes to produce testosterone, while FSH is crucial for spermatogenesis (sperm production).³
Male hypogonadism can be classified into two main types:⁴
- Primary hypogonadism (hypergonadotropic hypogonadism): This type originates from a problem within the testes themselves (testicular failure). The testes do not respond adequately to stimulation from the pituitary gland, leading to low testosterone and/or impaired sperm production, often accompanied by elevated levels of LH and FSH as the pituitary tries to compensate. Causes include genetic conditions like Klinefelter syndrome, undescended testicles (cryptorchidism), mumps orchitis (inflammation of the testicles due to mumps), hemochromatosis (iron overload), direct injury to the testicles, and side effects of cancer treatments like chemotherapy or radiation.⁴˒⁵
- Secondary hypogonadism (hypogonadotropic hypogonadism): This type results from dysfunction of the hypothalamus or the pituitary gland. These parts of the brain fail to produce sufficient GnRH, LH, or FSH, leading to inadequate stimulation of otherwise normal testes. Consequently, testosterone production and spermatogenesis are reduced, and LH and FSH levels are typically low or inappropriately normal. Causes include Kallmann syndrome (a genetic disorder affecting GnRH production and sense of smell), pituitary tumors or disorders, inflammatory diseases affecting the hypothalamus or pituitary (e.g., sarcoidosis), HIV/AIDS, certain medications (e.g., opioids, glucocorticoids), obesity, and aging.⁴˒⁵
The primary purpose of diagnosing and managing male hypogonadism is to alleviate symptoms, restore normal testosterone levels where appropriate, improve quality of life, and address potential long-term complications such as osteoporosis, changes in body composition, mood disturbances, and infertility.⁶ Treatment strategies vary depending on the cause, the patient’s age, symptoms, and fertility desires, and may include testosterone replacement therapy (TRT), lifestyle modifications, or treatments aimed at restoring fertility.²
Clinical Context
Male hypogonadism is a condition encountered in various clinical settings, presenting differently based on the age of onset and severity. Its clinical significance lies in its impact on sexual development, reproductive function, bone health, muscle mass, mood, and overall quality of life.1˒2
When it is used clinically/Relevant Medical Conditions: The diagnosis of male hypogonadism is considered when a male presents with symptoms suggestive of testosterone deficiency and/or infertility, supported by biochemical evidence of low testosterone levels.1 Symptoms vary by age:
- Fetal Development: Insufficient testosterone can lead to impaired growth of external sex organs, resulting in ambiguous genitalia or underdeveloped male genitals.2
- Puberty: Hypogonadism can cause delayed puberty, lack of normal development of secondary sexual characteristics (e.g., voice deepening, muscle mass development, growth of body/facial hair, penile/testicular growth), gynecomastia (breast tissue development), and disproportionately long limbs.2
- Adulthood: Symptoms can include decreased libido, erectile dysfunction, reduced energy levels, depression, infertility, loss of muscle mass and strength, decreased bone mineral density (osteoporosis), loss of body hair, gynecomastia, hot flashes, and difficulty concentrating.2˒6
Relevant medical conditions associated with or predisposing to hypogonadism include Klinefelter syndrome, Kallmann syndrome, pituitary tumors, testicular trauma or infection (e.g., mumps orchitis), hemochromatosis, chronic illnesses (e.g., HIV/AIDS, end-stage renal disease, severe COPD), type 2 diabetes, obesity, and use of certain medications like opioids or chronic glucocorticoids.1˒4
Patient Selection Criteria for Treatment: Treatment is generally recommended for men with symptomatic hypogonadism and unequivocally low testosterone levels, confirmed on at least two separate early morning measurements.1˒3 Asymptomatic men with only biochemical evidence of low testosterone may not always require treatment, and the decision is individualized.2 The goals of treatment are to alleviate symptoms, improve sexual function, bone density, muscle mass, and mood.3
Patient selection also considers fertility desires. Testosterone replacement therapy (TRT) suppresses spermatogenesis, so men desiring fertility may require alternative treatments like clomiphene citrate or gonadotropin therapy to stimulate endogenous testosterone production and sperm development.1˒3
Surgical Procedures (if applicable): Surgical procedures are not typically a primary treatment for hypogonadism itself, but may be relevant in specific contexts:
- Undescended Testicles (Cryptorchidism): Orchiopexy, a surgical procedure to bring the testicle(s) into the scrotum, is performed in childhood to reduce risks of infertility and testicular cancer, which can be associated with primary hypogonadism.2
- Pituitary Tumors: Surgical removal of a pituitary tumor causing secondary hypogonadism may sometimes restore normal pituitary function, although hormone replacement may still be necessary.4
Expected Outcomes: With appropriate treatment, many symptoms of hypogonadism can be improved or reversed. TRT can lead to significant improvements in libido, erectile function (in some cases), energy levels, mood, muscle mass, and bone mineral density.1˒3˒6 Effects on cognitive function and cardiovascular health are areas of ongoing research.3
For men with secondary hypogonadism due to reversible causes (e.g., medication-induced, obesity-related), addressing the underlying cause can sometimes restore normal testicular function. For those with primary hypogonadism or irreversible secondary hypogonadism, TRT is often a lifelong therapy. Outcomes regarding fertility depend on the specific cause and treatment approach; TRT impairs fertility, while other treatments may restore it in selected cases.1