Summary

Endocrine Society 2018 update to the 2010 guideline on testosterone therapy in men with hypogonadism. Diagnosis requires both symptoms/signs of testosterone deficiency AND unequivocally low, repeated morning fasting total testosterone; free testosterone is reserved for borderline values or altered SHBG. T therapy is indicated only for symptomatic hypogonadal men to restore secondary sex characteristics and correct symptoms, with specific contraindications and a structured monitoring plan targeting mid-normal serum T concentrations.

Key Recommendations

Diagnose hypogonadism only in men with symptoms/signs of T deficiency AND unequivocally and consistently low serum total or (when indicated) free testosterone.
Measure fasting morning total testosterone on two separate days using a CDC-certified accuracy-based assay to confirm diagnosis.
Measure free testosterone (by equilibrium dialysis or accurate calculation) when total T is near the lower limit of normal or SHBG is altered (obesity, T2DM, aging, HIV, hepatitis, hyperthyroidism, anticonvulsants).
Do not routinely screen the general male population for hypogonadism; reserve case detection for high-prevalence conditions (pituitary disease, HIV wasting, osteoporosis, opioid/glucocorticoid use, infertility).
Distinguish primary from secondary hypogonadism by measuring LH and FSH; in severe secondary hypogonadism (T<150 ng/dL), hyperprolactinemia, or panhypopituitarism, obtain pituitary MRI.
Obtain a karyotype in primary hypogonadism of unknown etiology, particularly when testicular volume <6 mL, to evaluate for Klinefelter syndrome.
Offer T therapy to symptomatic hypogonadal men to induce/maintain secondary sex characteristics and correct symptoms, choosing formulation by patient preference, pharmacokinetics, burden, and cost.
Do NOT start T therapy in men planning near-term fertility, breast/prostate cancer, palpable prostate nodule, PSA >4 ng/mL (or >3 ng/mL with high prostate cancer risk without urologic evaluation), elevated hematocrit, untreated severe OSA, severe LUTS, uncontrolled heart failure, MI/stroke within 6 months, or thrombophilia.
Do not routinely prescribe T to all men ≥65 with low T; offer individualized therapy only to those with consistent symptoms (e.g., low libido, unexplained anemia) and unequivocally low morning T.
Do not use T therapy to improve glycemic control in men with type 2 diabetes.
Consider short-term T therapy in HIV-infected men with low T and unexplained weight loss to promote weight/lean mass gain.
Aim for mid-normal serum T during treatment; monitor symptoms, T, hematocrit, and prostate at 3–12 months, at 1 year, then annually, and obtain urologic consult for PSA rise >1.4 ng/mL, confirmed PSA >4 ng/mL, or prostatic abnormality on DRE.

Thresholds & Doses

Lower limit of normal total testosterone (CDC-harmonized, healthy nonobese young men): 264 ng/dL (9.2 nmol/L).
Borderline total T zone requiring free T measurement: ~200–400 ng/dL.
Severe secondary hypogonadism warranting pituitary MRI: serum T <150 ng/dL (5.2 nmol/L).
Very small testes suggesting need for karyotype: <6 mL.
PSA contraindications to starting T: >4 ng/mL, or >3 ng/mL in men at high prostate cancer risk (without urologic evaluation).
Hematocrit threshold to stop T therapy: >54% (then evaluate for hypoxia/OSA, restart at reduced dose).
Baseline hematocrit relative contraindication: >48% (>50% at altitude).
Urologic referral triggers during first 12 months of T therapy: PSA increase >1.4 ng/mL above baseline, confirmed PSA >4.0 ng/mL, or prostatic abnormality on DRE.
T enanthate/cypionate: 150–200 mg IM every 2 weeks or 75–100 mg weekly.
T transdermal gel 1%: 50–100 mg daily; 1.62% gel: 20.25–81 mg daily; 2% gel: 40–70 mg daily.
Axillary T solution: 60 mg applied to axillae daily.
Buccal T tablets: 30 mg twice daily.
T pellets: 600–1200 mg SC, lasting 3–6 months.
Injectable T undecanoate (US): 750 mg IM at 0, 4 weeks, then every 10 weeks.
Nasal T gel: 11 mg two or three times daily.
Target mid-interval T on injectable enanthate/cypionate: 350–600 ng/dL (14.1–24.5 nmol/L); adjust dose if outside this range.
Hematocrit increase to ≥17.5 g/dL hemoglobin reported in some men on T therapy.
Prostate cancer screening start age in T-treated men: 55–69 yr generally; age 40 if increased risk (African American or first-degree relative with prostate cancer).
Acute illness/short-term opioid use suppresses T—delay testing until recovery.
Avoid T therapy in men with MI or stroke within the past 6 months.

Citations

Recommendation 1.1 — Diagnosis requires symptoms plus unequivocally low total/free T on repeat morning fasting measurements.
Recommendation 1.2 — Against routine population screening for hypogonadism.
Recommendation 1.3 — Use LH/FSH to distinguish primary from secondary hypogonadism.
Recommendation 2.1 and 2.2 — Indications and contraindications for T therapy; PSA, hematocrit, and cardiovascular cutoffs.
Recommendation 2.4 — Individualized T therapy for symptomatic men >65 years.
Recommendation 2.5 and 2.6 — Short-term T in HIV-associated weight loss; against T for glycemic control in T2DM.
Recommendations 3.1–3.2 and Table 9 — Monitoring plan, target mid-normal T, hematocrit and PSA thresholds for urological referral.
Tables 5–7 — T formulation pharmacology, doses, and conditions in which T is contraindicated.
Figure 1 — Diagnostic algorithm with TT lower limit 264 ng/dL and free T criteria.