What is the treatment for low testosterone levels?

Treatment for Low Testosterone Levels

For men with confirmed low testosterone and sexual dysfunction who desire improvement, initiate testosterone replacement therapy after discussing benefits and risks, but do not treat for non-sexual symptoms like fatigue, cognitive issues, or physical function alone. 1

Diagnostic Confirmation Required Before Treatment

Before initiating any treatment, confirm the diagnosis with proper testing:

• Measure morning total testosterone (between 8-10 AM) on at least two separate occasions to confirm persistently low levels 1, 2
• Measure serum luteinizing hormone (LH) in all patients with low testosterone to determine if hypogonadism is primary (testicular) or secondary (hypothalamic-pituitary) 1
• Measure serum prolactin if LH is low or low-normal, as elevated prolactin may indicate pituitary pathology requiring endocrine referral 1
• In obese men, measure free testosterone by equilibrium dialysis in addition to total testosterone, as obesity can lower sex hormone-binding globulin and falsely reduce total testosterone while free testosterone remains normal 1
• Order pituitary MRI if total testosterone is <150 ng/dL with low/low-normal LH, regardless of prolactin levels, to rule out non-secreting pituitary adenomas 1

When to Treat: Evidence-Based Indications

The 2020 American College of Physicians guideline provides the most recent high-quality recommendations:

• Treat only for sexual dysfunction improvement in men with confirmed low testosterone who specifically desire better sexual function 1
• Do NOT initiate testosterone for energy, vitality, physical function, or cognition, as evidence does not support benefit for these symptoms 1, 3
• Consider fertility preservation evaluation before starting treatment in men interested in maintaining fertility, as testosterone therapy suppresses spermatogenesis 1, 4

Absolute Contraindications to Treatment

Do not start testosterone therapy in men with: 1, 5, 2, 6

• Breast or prostate cancer
• Prostate-specific antigen (PSA) >3 ng/mL without urological evaluation (>4 ng/mL in general population)
• Palpable prostate nodule or induration
• Hematocrit >50% (or >54% per some guidelines)
• Untreated severe obstructive sleep apnea
• Severe lower urinary tract symptoms (International Prostate Symptom Score >19)
• Class III or IV heart failure

Treatment Selection: Formulation Choice

Choose intramuscular testosterone over transdermal formulations as first-line therapy due to significantly lower cost with equivalent clinical effectiveness and safety profiles 1, 7

Alternative formulations when intramuscular is not suitable: 1, 8

• Transdermal gel: Provides stable daily testosterone levels but costs more, has variable absorption, and carries risk of transfer to others (particularly children and women who must avoid contact with application sites)
• Transdermal patches: Minimize transfer risk compared to gels but may cause skin irritation and adherence problems
• Implantable pellets: Offer long-term delivery but require procedural implantation

Treatment Goals and Monitoring

Target mid-normal range testosterone levels during treatment rather than supraphysiologic levels 1, 5, 2

Initial Monitoring Schedule:

• Reassess symptoms at 12 months after treatment initiation 1, 7
• Measure testosterone levels at 2-3 months after starting therapy to ensure therapeutic range is achieved 1
• Check hematocrit, PSA, and perform digital rectal examination at baseline, 3 months, 6 months, and 12 months 6
• Monitor for cardiovascular events throughout treatment 7

Treatment Discontinuation:

Stop testosterone therapy if no improvement in sexual function occurs within 12 months, as continued treatment is unlikely to provide benefit 1, 7

Special Populations

Young Men Desiring Fertility:

For young men with hypogonadism who want to preserve fertility, avoid traditional testosterone replacement as it suppresses spermatogenesis through negative feedback 4

Consider alternative agents: 4

• Selective estrogen receptor modulators (can be used in men with low/low-normal LH)
• Human chorionic gonadotropin
• Aromatase inhibitors
• Intranasal testosterone (less suppressive)

Obese Men:

Measure free testosterone by equilibrium dialysis to distinguish true hypogonadism from low total testosterone due to reduced sex hormone-binding globulin 1

Initiate testosterone replacement only when free testosterone is frankly low on two separate assessments after completing hypogonadism workup 1

Testosterone replacement in obese hypogonadal men has demonstrated improvements in weight, fasting glucose, insulin resistance, triglycerides, HDL cholesterol, lean body mass, and waist circumference 1

Critical Safety Considerations

Transfer Risk with Topical Formulations:

The FDA requires warnings that topical testosterone can transfer to others through skin contact, causing virilization in children (enlarged genitals, early pubic hair, aggressive behavior) and women (hirsutism, acne) 8

Prevention measures: 8

• Apply only to shoulders and upper arms that will be covered by clothing
• Wash hands immediately with soap and water after application
• Cover application area with clothing after gel dries
• Wash application area before anticipated skin-to-skin contact
• If contact occurs, the exposed person should wash the area immediately with soap and water

Age-Related Considerations:

FDA labeling restricts testosterone products to men with low testosterone due to known medical causes, not age-related decline alone 1, 3

The evidence for long-term safety in men over 75 years is limited 3

Common Pitfalls to Avoid

• Do not use screening questionnaires as substitutes for laboratory testosterone measurement or as sole basis for treatment decisions 1
• Do not treat based on symptoms alone without confirmed biochemical hypogonadism on repeated testing 1, 5, 2
• Do not overlook underlying causes such as medications (chronic opioids, corticosteroids), obesity, diabetes, HIV, or pituitary disorders that may require specific management 1
• Do not forget to optimize sleep before considering testosterone replacement, as poor sleep contributes to low testosterone 7