Updated October 2025

Andrology | Endocrinology

Male Hypogonadism: Diagnostic Criteria and Evidence for Testosterone Therapy

Diagnose hypogonadism only when consistent symptoms/signs coexist with repeatedly low morning testosterone. Confirm etiology (primary vs secondary) and address reversible causes. Testosterone therapy improves anemia and modestly improves sexual function/energy in symptomatic men; cardiovascular risk appears neutral in contemporary trials. Monitor hematocrit, PSA/prostate risk, fertility, and symptom response with a structured plan.

Clinical question

How should clinicians diagnose male hypogonadism and when does testosterone therapy provide meaningful benefit and acceptable risk?

HypogonadismTestosteroneAnemiaErectile DysfunctionEndocrinologyMen's Health

Key points

Anchor diagnosis to symptoms + biochemistry

Only diagnose hypogonadism with consistent symptoms/signs and repeatedly low morning total testosterone, adjusting for SHBG if needed. Distinguish primary vs secondary with LH/FSH to guide workup and treatment ^[4], ^[5].

Therapeutic efficacy: focused gains

TRT corrects anemia in a meaningful minority and modestly improves sexual function and energy; cognitive outcomes generally unchanged in trials of older men ^[1], ^[2], ^[3].

Safety signal is acceptable with monitoring

Contemporary evidence suggests no significant increase in cardiovascular risk overall with TRT in appropriately selected men; still monitor hematocrit, prostate, edema, and fertility implications ^[1], ^[6].

Standardize thresholds and re-testing

Use early morning sampling on two occasions; T <8 nmol/L (~231 ng/dL) strongly supports deficiency, >12 nmol/L (~346 ng/dL) usually normal; in-between values need repeat testing and clinical correlation ^[7], ^[4].

Guideline heterogeneity—be explicit

Specialty society criteria vary; document symptom profile, assay timing/conditions, and confirmatory labs to ensure reproducibility and defensibility of the diagnosis ^[8], ^[9], ^[4].

Evidence highlights

≈10–15% absolute increase vs placebo in hypogonadal men with anemia ^[1], ^[2]

Anemia correction with TRT

≈2–3% absolute reduction vs placebo ^[1], ^[2]

Prevention of incident anemia

Small but statistically significant improvement ^[3]

Sexual function

Symptoms + 2 low morning T values (preferably with LH/FSH) ^[4], ^[5]

Diagnostic rule

Diagnostic Workflow

From Suspicion to Diagnosis

A concise, stepwise approach that aligns clinical features with reproducible biochemical evidence and etiologic classification.

Identify compatible symptoms and signs

Common features: low libido, erectile dysfunction, decreased morning erections, fatigue, depressed mood, decreased muscle mass/strength, low bone density, anemia. In postpubertal men, symptom specificity varies; sexual symptoms are more predictive of low T ^[5], ^[4].

Obtain two early morning total testosterone values

Draw between 7–10 AM on separate days, fasting when feasible, and avoid acute illness. Low T must be reproducible to support diagnosis ^[4], ^[5].

Interpret thresholds with context

<8 nmol/L (~231 ng/dL) strongly supports hypogonadism; >12 nmol/L (~346 ng/dL) usually excludes it; borderline values warrant repeat testing and assessment of SHBG/free T if discordant with symptoms ^[7], ^[4].

Determine etiology with gonadotropins

Primary hypogonadism: low T with high LH/FSH. Secondary hypogonadism: low T with low/normal LH/FSH. Etiology guides further workup (prolactin, iron studies, pituitary imaging when indicated) and management ^[5], ^[4].

Address reversible contributors

Obesity, systemic illness, OSA, hyperprolactinemia, opioids/glucocorticoids, alcohol, and acute stress can suppress T; optimize these factors before or alongside therapy ^[4].

Therapeutic Evidence and Practice

Testosterone Therapy: Who Benefits and How to Monitor

Evidence-based indications, expected benefits, and a structured monitoring plan for safe prescribing.

Candidates for TRT

Men with symptoms/signs consistent with T deficiency and two low morning T results ^[4].

Primary or secondary hypogonadism after addressing reversible causes ^[4], ^[5].

Discuss fertility: TRT suppresses spermatogenesis; avoid if near-term fertility desired ^[4].

Efficacy: What to expect

Anemia: TRT corrected anemia in ≈10–15% more men than placebo and prevented incident anemia by ≈2–3% in hypogonadal men; small energy gains; no cognitive benefit in TRAVERSE substudies ^[1], ^[2].

Sexual function: statistically significant, clinically modest improvement in erectile function/libido vs placebo ^[3].

Body composition and bone: modest increases over time; symptomatic impact varies (guideline-based synthesis) ^[4].

Safety and cardiovascular risk

Contemporary evidence shows no significant increase in cardiovascular risk overall with TRT in hypogonadal men when appropriately selected and monitored ^[6], ^[1].

Monitor for erythrocytosis, edema, acne, gynecomastia, infertility; prostate-related monitoring per age/risk ^[4].

Baseline before starting

Confirm: 2 morning total T; consider free T if SHBG abnormal ^[4].

LH, FSH to classify primary vs secondary; prolactin if secondary; consider iron studies and pituitary evaluation as indicated ^[5], ^[4].

Hematocrit/hemoglobin, PSA and DRE per risk, CMP, lipid panel; consider sleep apnea screening and CV risk assessment ^[4].

Monitoring after initiation

Hematocrit: at 3–6 months, then 6–12 months; hold or reduce dose if Hct >54% ^[4].

Testosterone trough/peak depending on formulation to target mid-normal physiologic range ^[4].

PSA/prostate assessment per guidelines and shared decision-making; evaluate LUTS progression ^[4].

Track symptoms, BP/edema, acne, mood/energy, and adherence; reassess benefit–risk periodically ^[4], ^[10].

When NOT to start TRT

Desire for fertility in near term; consider alternatives (e.g., hCG, SERMs).

Untreated severe OSA, Hct >50–52%, uncontrolled heart failure, active prostate or breast cancer, recent major CV event until stabilized (contextual and guideline-based) ^[4].

Special Topics

Navigating Guideline Variability and Borderline Cases

Standardize your internal approach amid heterogeneous criteria.

Acknowledge heterogeneity

Society guidelines differ in thresholds and testing algorithms; document timing, assays, and symptom profiles to enhance reproducibility and medico-legal clarity ^[8], ^[9].

Borderline testosterone

For 8–12 nmol/L (~231–346 ng/dL), repeat morning T, evaluate SHBG and calculate free T, and weigh symptom specificity (sexual symptoms carry more diagnostic weight) before labeling deficiency ^[7], ^[4], ^[5].

Older men with comorbidity

In men with multimorbidity, prioritize anemia correction and symptomatic sexual benefits, while closely monitoring hematocrit and cardiovascular status; cognitive gains are unlikely ^[1], ^[2], ^[3].

References

Source material

Primary literature that informs this article.