What is the primary management approach for males with low testosterone (hypogonadism)?

Management of Low Testosterone in Males

The primary management approach for males with confirmed hypogonadism is testosterone replacement therapy (TRT) after proper diagnostic confirmation with two morning testosterone measurements below 300 ng/dL, presence of symptoms, and exclusion of contraindications. 1

Diagnostic Confirmation Before Treatment

Before initiating any therapy, you must establish the diagnosis properly:

• Obtain two separate morning (8:00-10:00 AM) total testosterone measurements on different days, both showing levels <300 ng/dL 1, 2
• Confirm presence of symptoms: reduced libido, erectile dysfunction, fatigue, decreased muscle mass, mood changes, or unexplained anemia 1, 3
• Measure serum LH to distinguish primary (elevated LH) from secondary (low/normal LH) hypogonadism, as this affects fertility counseling 1, 2

Critical pitfall: Never treat based on symptoms alone without laboratory confirmation, and avoid testing during acute illness as this artificially suppresses testosterone levels 2, 4

Pre-Treatment Evaluation

Before starting TRT, complete the following mandatory assessments:

• Measure baseline hemoglobin/hematocrit - withhold therapy if Hct >50% until etiology investigated 1, 4
• Assess cardiovascular risk factors including lipids, blood pressure, diabetes status, and smoking history 1
• Measure PSA and perform digital rectal exam in men over 40 years to exclude prostate cancer 1, 4
• Reproductive health evaluation in men interested in fertility: testicular exam, FSH measurement, and semen analysis if indicated 1, 2
• Measure serum prolactin if LH is low or low-normal to screen for prolactinoma 1
• Obtain pituitary MRI if testosterone <150 ng/dL with low/normal LH, regardless of prolactin level 1

Absolute Contraindications to TRT

Do not initiate testosterone therapy in men with: 5

• Breast or prostate cancer
• PSA >4 ng/dL (or >3 ng/dL in high-risk men without urological evaluation)
• Elevated hematocrit
• Untreated severe obstructive sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled heart failure
• Myocardial infarction or stroke within 6 months
• Men planning fertility in the near term (TRT suppresses spermatogenesis)

Testosterone Replacement Formulations

Multiple FDA-approved formulations are available: 6, 7

Topical testosterone gel (1.62%):

• Starting dose 40.5 mg daily applied to shoulders/upper arms
• Adjustable between 20.25-81 mg based on levels
• Major warning: Risk of secondary exposure to children - patients must wash hands immediately and cover application sites 7

Intramuscular testosterone cypionate:

• Indicated for both primary and secondary hypogonadism
• Produces greatest increases in hemoglobin/hematocrit requiring closer monitoring 1, 6

Target testosterone levels: Mid-to-upper normal range (avoid supraphysiologic levels) 4, 5

On-Treatment Monitoring Protocol

First follow-up at 1-2 months, then every 3-6 months for the first year, then annually: 4, 5

• Measure serum testosterone at 14 and 28 days after starting or dose adjustment to guide titration 7
• Monitor hematocrit - if >54%, reduce dose or temporarily discontinue 1
• Assess symptom response: sexual function, energy, mood, muscle strength 1, 5
• Monitor PSA and perform digital rectal exam 1, 4
• Evaluate for adverse effects: gynecomastia, sleep apnea symptoms, fluid retention, skin reactions 4

Critical monitoring point: Injectable testosterone carries highest risk of polycythemia and may require phlebotomy if hematocrit remains elevated despite dose reduction 1

Expected Benefits of TRT

Patients should be counseled that TRT may improve: 1, 5, 8

• Erectile function and libido
• Bone mineral density
• Lean body mass and muscle strength
• Anemia
• Depressive symptoms and quality of life
• Energy levels and fatigue

Alternative Management for Fertility Preservation

For men desiring fertility, TRT is contraindicated as it suppresses spermatogenesis: 1, 4

• Refer to reproductive endocrinology for gonadotropin therapy or selective estrogen receptor modulators (SERMs)
• These agents stimulate endogenous testosterone production while preserving fertility 1
• Measure FSH and consider semen analysis before any treatment 1, 2

Special Populations Requiring Endocrinology Referral

Refer to endocrinology if: 1

• Persistently elevated prolactin levels
• Elevated baseline estradiol
• Testosterone <150 ng/dL with low/normal LH
• Hypergonadotropic hypogonadism with severe oligospermia or azoospermia requiring genetic testing

Cardiovascular Safety Considerations

Current evidence does not support increased cardiovascular/cerebrovascular risk with TRT in the short-to-medium term: 8

• Meta-analysis of 13 studies showed no difference in cardiovascular events (odds ratio 1.07,95% CI 0.81-1.42) 8
• However, use caution in men with congestive heart failure or recent cardiovascular events due to potential fluid retention 4, 5
• Low testosterone itself is associated with increased all-cause and cardiovascular mortality, though causality remains uncertain 1

Common pitfall: Clinician concerns about cardiovascular risk often lead to undertreatment of appropriate candidates, despite lack of definitive evidence supporting this concern 1