Classification of Hypogonadism
Hypogonadism is further classified into two main types based on the underlying cause:
Primary (Hypergonadotropic) Hypogonadism
- Primary hypogonadism refers to testicular failure where the testes cannot produce adequate testosterone despite maximal pituitary stimulation, resulting in elevated LH and FSH levels together with low testosterone. 2
- Common causes include prior chemotherapy, pelvic radiation, cryptorchidism, Klinefelter syndrome (47,XXY), testicular torsion, bilateral orchitis, and Y-chromosome microdeletions. 2
Secondary (Hypogonadotropic) Hypogonadism
- Secondary hypogonadism results from hypothalamic or pituitary dysfunction, characterized by low testosterone with inappropriately low or normal LH and FSH levels. 2, 3
- The most common causes in adults are functional: obesity (which increases aromatization of testosterone to estradiol), type 2 diabetes, metabolic syndrome, chronic opioid use, glucocorticoid excess, and chronic systemic illnesses. 2
- Structural causes include pituitary adenomas, traumatic brain injury, pituitary surgery or radiation, and congenital conditions like Kallmann syndrome. 2
Diagnostic Criteria
Biochemical hypogonadism is diagnosed when both of two separate morning total testosterone measurements (8–10 AM) are <300 ng/dL (10.5 nmol/L) AND the patient has characteristic symptoms such as reduced libido or erectile dysfunction. 1, 2, 3
- The distinction between primary and secondary hypogonadism is made by measuring serum LH and FSH after confirming low testosterone on two occasions. 2, 3
- Elevated LH/FSH indicates primary (testicular) hypogonadism, while low or normal LH/FSH indicates secondary (hypothalamic-pituitary) hypogonadism. 2
Alternative Terms
- Testosterone deficiency syndrome and androgen deficiency are also used interchangeably with hypogonadism. 4
- Late-onset hypogonadism (LOH) or symptomatic LOH (SLOH) specifically refers to age-related testosterone decline that causes detrimental physiological and mental effects. 5
- Andropause is sometimes used to describe age-associated hypogonadism, though this may present a mixed picture with low testosterone and low-to-normal gonadotropin levels. 3