Overview.
Male hypogonadism is defined by persistently low serum testosterone combined with symptoms of androgen deficiency. It affects approximately 2-4% of men overall, rising to 20-40% in men over 60. Distinguishing primary (testicular) from secondary (pituitary-hypothalamic) causes is critical as it determines both workup and treatment.
Testosterone is produced primarily by Leydig cells in the testes, regulated by the hypothalamic-pituitary-gonadal axis. LH from the pituitary drives testosterone production; FSH drives spermatogenesis. Primary hypogonadism is testicular failure (high LH/FSH, low testosterone). Secondary hypogonadism is pituitary or hypothalamic dysfunction (low/normal LH/FSH, low testosterone). Diagnosis requires two fasting morning measurements on separate occasions.
Prevalence: Estimated prevalence of 2-4% in adult men overall. Rises to 20-40% in men over 60. Higher in men with obesity, type 2 diabetes, or chronic illness. Significantly underdiagnosed.
Medical name: Male Hypogonadism (Testosterone Deficiency)
Symptoms.
Early warnings
- Reduced morning erections
- Decreased libido
- Low energy and fatigue
- Mild depression or irritability
- Reduced shaving frequency
- Decline in athletic or gym performance
Classic symptoms
- Erectile dysfunction
- Loss of libido
- Hot flushes (in severe/secondary cases)
- Loss of body and facial hair
- Reduced testicular size
- Gynecomastia
- Reduced muscle mass, increased body fat
- Decreased bone density (osteopenia/osteoporosis)
- Impaired concentration and memory
- Depression and mood changes
- Infertility (azoospermia or oligospermia)
Progression
Untreated hypogonadism leads to progressive muscle loss, visceral adiposity, bone loss, worsening metabolic syndrome, and declining quality of life. Secondary hypogonadism from a pituitary tumor requires urgent imaging.
Risk factors.
- Obesity (BMI >30 markedly suppresses testosterone)
- Type 2 diabetes and metabolic syndrome
- Age >45
- Chronic opioid or glucocorticoid use
- Klinefelter syndrome (XXY) — most common genetic cause
- Prior chemotherapy or pelvic radiation
- Cryptorchidism (undescended testes)
- Obstructive sleep apnea
- Hemochromatosis
- Chronic kidney or liver disease
Lab interpretation.
Key biomarkers
- Total Testosterone — Low: <300 ng/dL per AUA, <350 ng/dL per EAU/Endocrine Society; measured fasting 07:00-11:00 on two separate occasions (primary)
- Free Testosterone — Low; measured by equilibrium dialysis or calculated from total T + SHBG + albumin; critical when SHBG is altered (primary)
- LH (Luteinizing Hormone) — Elevated in primary hypogonadism (testicular failure); low or inappropriately normal in secondary (pituitary/hypothalamic) (primary)
- FSH (Follicle-Stimulating Hormone) — Elevated in primary hypogonadism; low/normal in secondary; markedly elevated FSH with azoospermia suggests irreversible spermatogenic failure (primary)
- SHBG — Elevated in aging/liver disease (lowers free T); low in obesity/diabetes (raises free T bioavailability); context determines free T interpretation (secondary)
- Prolactin — Should be measured in all secondary hypogonadism; >25 ng/mL requires pituitary MRI to exclude prolactinoma (secondary)
- Estradiol — Elevated in obesity-related hypogonadism (aromatization); also elevated in feminizing tumors (secondary)
Diagnostic criteria
- Symptoms AND signs of testosterone deficiency must be present (not lab values alone)
- Two fasting morning total testosterone measurements on separate days
- AUA threshold: total T <300 ng/dL (PMID: 29601923)
- Endocrine Society threshold: <350 ng/dL (PMID: 29562364)
- Primary: elevated LH + elevated FSH + low T (testicular failure)
- Secondary: low/normal LH + low/normal FSH + low T (pituitary/hypothalamic failure)
Recommended panels
When & next steps.
When to test
- Symptoms of low testosterone: reduced libido, erectile dysfunction, fatigue, mood changes
- Unexplained infertility in a male partner
- Osteoporosis or fragility fracture in a man under 70
- Gynecomastia without another explanation
- Chronic opioid or glucocorticoid use
- Obesity, type 2 diabetes, or metabolic syndrome with fatigue or sexual symptoms
- Klinefelter syndrome or other known gonadal abnormality
If suspected
- Order two fasting morning (07:00-11:00) total testosterone measurements on separate days
- Add: LH, FSH, prolactin, SHBG on the same draw
- Review all medications: opioids, glucocorticoids, anabolic steroids cause iatrogenic suppression
- Calculate free testosterone if total T borderline (280-400 ng/dL range)
- If secondary pattern (low LH/FSH): measure remaining pituitary hormones and consider MRI
If confirmed
- Treat underlying cause first if reversible (weight loss for obesity, dopamine agonist for prolactinoma)
- Testosterone replacement therapy (TRT): topical, injectable, or implant formulations
- Use hCG (not TRT) if fertility preservation is desired
- Monitor: testosterone levels, hematocrit, PSA, mood and symptoms at 3 months then annually
- Never initiate TRT without confirmatory diagnosis on two separate fasting morning occasions
FAQs.
Can I have hypogonadism if my testosterone is within the lab reference range?
Not by clinical guidelines. The diagnosis requires both low testosterone (below guideline thresholds, not just lab range) AND symptoms. Free testosterone and SHBG context can clarify borderline total T results.
Does testosterone therapy affect fertility?
Yes — exogenous testosterone suppresses LH and FSH, stopping sperm production. Men who want fertility should use hCG or clomiphene rather than testosterone. Discuss this before starting TRT.
Is low T the same as andropause?
Andropause is an informal term for age-related testosterone decline. While testosterone does decline ~1% per year after age 30, clinical hypogonadism requires both symptomatic and confirmed biochemical diagnosis. Most age-related decline does not meet criteria for treatment.