What is Hypogonadism
Hypogonadism is a clinical condition characterized by both specific symptoms AND biochemically confirmed testosterone deficiency that impacts multiple organ systems and quality of life. 1
Core Definition
Hypogonadism requires two essential components for diagnosis:
- Persistent specific symptoms including diminished libido, erectile dysfunction, reduced muscle mass and strength, increased body fat, diminished bone density, decreased energy, increased fatigue, depressed mood, and impaired cognition 1
- Laboratory confirmation of decreased morning total testosterone levels measured on at least two separate days 2, 3
The condition represents a failure to produce physiological concentrations of testosterone, distinguishing it from normal age-related decline 4.
Classification by Anatomical Origin
Primary (Hypergonadotropic) Hypogonadism
- Caused by testicular failure resulting in low testosterone with elevated LH and FSH levels as the pituitary attempts to compensate 1, 5
- Congenital causes include Klinefelter's syndrome, cryptorchidism, bilateral torsion, vanishing testis syndrome, and chromosomal abnormalities 1, 3
- Acquired causes include orchitis, orchiectomy, testicular trauma, radiation damage, chemotherapy, and toxic damage from alcohol or heavy metals 1, 3
Secondary (Hypogonadotropic) Hypogonadism
- Results from hypothalamic-pituitary-gonadal (HPG) axis dysfunction with low testosterone and inappropriately low or normal LH/FSH levels 1, 5
- Congenital causes include idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, and LHRH deficiency 1, 3
- Acquired causes include pituitary tumors, traumatic brain injury, pituitary-hypothalamic injury from radiation, and drug-induced causes 1, 6
- Drug-induced forms result from opiate use, GnRH agonists/antagonists, glucocorticoids, estrogens, and anabolic steroids 1
Functional Hypogonadism
- Occurs when low testosterone develops without organic alterations in the HPG axis, typically as a consequence of comorbidities 1
- Commonly correlates with obesity and metabolic disorders including metabolic syndrome and diabetes 2, 7
- Distinguishing feature: addressing underlying conditions (weight loss, metabolic disease management) can normalize both testosterone and LH levels 5
Compensated Hypogonadism
- Characterized by normal testosterone levels with elevated LH production, indicating the pituitary is working harder to maintain normal testosterone 1
Critical Diagnostic Distinction: The Role of LH
LH levels are the critical laboratory marker that distinguishes primary from secondary hypogonadism, and this distinction fundamentally determines treatment strategy—particularly whether fertility preservation is possible. 5
- Elevated LH/FSH = Primary hypogonadism → testosterone replacement is the only option; sperm banking should be offered before treatment if any residual spermatogenesis exists 5
- Low or inappropriately normal LH/FSH = Secondary hypogonadism → patients can potentially achieve both normal testosterone levels AND fertility with gonadotropin therapy (hCG and FSH) 5
- Low-normal LH with metabolic comorbidities = Functional hypogonadism → address underlying conditions first; weight loss can reverse the condition 5
Clinical Impact Beyond Sexual Function
Testosterone is not just a sex hormone—it has key actions on metabolism, vasculature, brain function, bone density, and body composition. 8
Hypogonadism can be present in up to 40% of men presenting with couple infertility, as testosterone is the major androgen regulating spermatogenesis. 9
The timing of onset (fetal, prepubertal, or postpubertal) significantly impacts fertility potential and treatment success rates. 9