What is hypogonadotropic hypogonadism (Low Luteinizing Hormone (LH) in males)?

Low LH in Males: Hypogonadotropic Hypogonadism

Low LH in males indicates secondary (hypogonadotropic) hypogonadism, a condition where the hypothalamic-pituitary axis fails to adequately stimulate the testes, resulting in low testosterone despite inappropriately low or normal gonadotropin levels—this distinction from primary hypogonadism is critical because it determines whether fertility can be restored. 1

Pathophysiology and Classification

Low LH represents dysfunction at the hypothalamic-pituitary level rather than testicular failure. 1, 2 The key diagnostic feature is that LH and FSH levels are either frankly low or inappropriately normal despite documented low testosterone—this paradoxical pattern indicates the pituitary is not responding appropriately to the low testosterone signal. 1, 3

The European Association of Urology emphasizes that LH levels are the critical laboratory marker distinguishing treatment pathways: patients with secondary hypogonadism can potentially achieve both normal testosterone AND fertility with appropriate gonadotropin therapy, unlike primary hypogonadism where only testosterone replacement is possible. 1

Types of Hypogonadotropic Hypogonadism

• Congenital forms include idiopathic hypogonadotropic hypogonadism, Kallmann syndrome (with anosmia), and GnRH/gonadotropin deficiency 2, 4, 5

• Acquired forms result from pituitary tumors (especially prolactinomas), sellar/hypothalamic lesions, pituitary surgery, head trauma, cranial radiation, infiltrative diseases, hemochromatosis, and drug-induced causes 2, 3, 5

• Functional hypogonadism occurs with low-normal LH levels secondary to obesity, metabolic syndrome, diabetes, chronic opioid use, glucocorticoids, or excessive exercise—this form is potentially reversible with treatment of underlying conditions 6, 2, 7

Diagnostic Algorithm

Step 1: Confirm Hypogonadism Biochemically

• Obtain two morning total testosterone measurements on separate days showing levels below normal range 1
• Testosterone testing must be avoided during acute illness as it can spuriously lower levels 6

Step 2: Assess for Specific Symptoms

The Endocrine Society requires presence of specific symptoms: 1

• Reduced libido
• Erectile dysfunction
• Decreased spontaneous erections
• Additional symptoms may include decreased energy, reduced muscle mass/strength, hot flushes, concentration difficulties, and sleep disturbances 6, 2

Step 3: Measure LH and FSH to Classify

• Low or inappropriately normal LH/FSH with low testosterone = Secondary (hypogonadotropic) hypogonadism 1, 3
• Elevated LH/FSH with low testosterone = Primary hypogonadism 1
• The term "inappropriately normal" is crucial—gonadotropins in the normal reference range are actually abnormal when testosterone is low, as the pituitary should be maximally stimulating the testes 3, 7

Step 4: Identify Underlying Cause

• Evaluate for pituitary disorders, surgical history, medications affecting the HPG axis (opiates, GnRH agonists/antagonists, glucocorticoids, anabolic steroids) 6, 2
• Assess for metabolic comorbidities: measure BMI, waist circumference, screen for obesity, metabolic syndrome, and diabetes 6
• Consider prolactin levels to exclude prolactinoma 3, 5
• Brain/pituitary MRI if structural lesion suspected 5

Treatment Strategy Based on Fertility Goals

If Fertility NOT Desired

Testosterone replacement therapy is the treatment of choice to restore sexual function, energy, muscle mass, and bone density. 4, 3

• FDA-approved indication: testosterone cypionate injection for hypogonadotropic hypogonadism (congenital or acquired) due to idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury 4
• Injectable testosterone esters are first-line treatment 3

Critical caveat: Testosterone therapy will suppress the HPG axis and eliminate any residual spermatogenesis, making this choice irreversible for fertility unless treatment is discontinued. 2

If Fertility IS Desired

Combined hCG and FSH therapy provides optimal outcomes for restoring both testosterone levels and spermatogenesis. 1, 8

• hCG stimulates testosterone production (mimicking LH action) 8
• FSH directly stimulates spermatogenesis 8
• Treatment duration typically 12-24 months promotes testicular growth in nearly all patients, spermatogenesis in approximately 80%, and pregnancy rates around 50% 8
• Success rates are higher in post-pubertal onset HH, larger baseline testicular volume, higher baseline inhibin B levels, and absence of cryptorchidism history 8

The pituitary-testicular axis maintains physiological negative feedback even in hypogonadotropic hypogonadism—higher residual FSH or LH levels during testosterone replacement significantly decrease the chance of achieving normal testosterone levels, indicating inadequate replacement. 9

For Functional Hypogonadism with Low-Normal LH

Address underlying conditions FIRST before considering testosterone therapy: weight loss, metabolic disease management, discontinuation of offending medications, and treatment of sleep apnea can normalize both testosterone and LH levels. 1, 2

• This approach may restore the HPG axis without lifelong hormone replacement 7
• If symptoms persist despite optimization of comorbidities, consider combining lifestyle interventions with testosterone therapy 1

Common Pitfalls

• Measuring testosterone during acute illness produces falsely low results and should be avoided 6
• Assuming normal-range LH is reassuring when testosterone is low—this represents inappropriate pituitary response 3, 7
• Starting testosterone without discussing fertility eliminates future reproductive options 2
• Failing to identify reversible causes in functional hypogonadism misses opportunity to restore natural HPG axis function 2, 7