How do I manage low testosterone levels?

Management of Low Testosterone Levels

Begin testosterone replacement therapy only if you have confirmed testosterone deficiency with two separate morning measurements below 300 ng/dL AND clinical symptoms—target mid-normal testosterone levels of 450-600 ng/dL during treatment. 1

Diagnostic Confirmation Required Before Treatment

You must establish the diagnosis with precision before initiating therapy:

• Obtain two separate morning testosterone measurements (8-10 AM) showing levels below 300 ng/dL, using the same laboratory and methodology if possible 1, 2
• Document clinical symptoms: reduced libido, erectile dysfunction, decreased energy/endurance, fatigue, loss of muscle mass, depression, poor concentration, or impaired memory 1, 2
• Measure serum LH and FSH to distinguish primary testicular failure (high LH/FSH) from secondary hypothalamic-pituitary dysfunction (low or normal LH/FSH) 2, 3
• Check serum prolactin if LH/FSH are low or low-normal to screen for hyperprolactinemia 2, 3

Critical pitfall to avoid: Never measure testosterone at random times—afternoon or evening measurements are physiologically lower and lead to false-positive diagnoses 2. The morning timing is non-negotiable due to diurnal variation.

Special Consideration for Obesity

If the patient is obese, the diagnostic approach changes:

• Measure free testosterone by equilibrium dialysis and SHBG in addition to total testosterone 2, 3
• Obesity-related low total testosterone may reflect low SHBG with normal free testosterone 2
• Only proceed with treatment if free testosterone is also low on at least two separate assessments 2

Baseline Testing Before Initiating Therapy

Before starting testosterone, obtain:

• Hemoglobin/hematocrit to establish baseline and monitor for polycythemia 4, 3
• PSA testing if patient is over 40 years old 4, 2
• Cardiovascular risk factor assessment 4

Absolute Contraindications to Testosterone Therapy

Do not initiate testosterone therapy in men with: 5, 6

• Breast cancer or prostate cancer
• PSA >3 ng/mL without urological evaluation 6
• Erythrocytosis (hematocrit >50%) 6
• Untreated obstructive sleep apnea 6
• Severe lower urinary tract symptoms (IPSS >19) 6
• Class III or IV heart failure 6
• Men currently trying to conceive—exogenous testosterone interrupts spermatogenesis 1

Treatment Selection and Dosing

Use transdermal testosterone preparations (gels or patches) as first-line therapy due to steady-state pharmacokinetics: 4

• Target testosterone levels in the mid-normal range (450-600 ng/dL) during treatment 1, 4, 3
• Apply gel to shoulders and upper arms only, areas that will be covered by a short-sleeve t-shirt 5
• Wash hands immediately with soap and water after application 5
• Cover application area with clothing after gel dries 5

Common pitfall: Skin reactions are more common with patches than gels 4. Cost varies widely among formulations and may limit use 7.

Mandatory Lifestyle Modifications

Counsel all men with testosterone deficiency on lifestyle modifications as a treatment strategy: 1

• Weight loss through low-calorie diets improves testosterone levels in obese patients with secondary hypogonadism 2, 3
• Regular physical activity provides similar benefits, though testosterone increases are typically modest (1-2 nmol/L) 2
• High BMI coupled with low testosterone increases cardiovascular event risk 1

Monitoring Protocol During Treatment

Schedule first follow-up at 1-2 months to assess efficacy and consider dose adjustments: 4

• Check testosterone levels at 2-3 months and after any dose change to ensure mid-normal range is achieved 4, 3
• Once stable levels confirmed, monitor every 6-12 months 4
• Monitor hemoglobin/hematocrit—polycythemia may require temporary discontinuation, dose reduction, or phlebotomy 4, 3
• Monitor PSA in men over 40 years 2, 3
• Measure serum estradiol if breast symptoms or gynecomastia develop 2

Cardiovascular and Prostate Cancer Counseling

Counsel patients that current evidence does not definitively demonstrate testosterone therapy increases cardiovascular risk: 1

• Untreated low testosterone is associated with increased risk of major adverse cardiovascular events (MACE) 1
• Studies measuring cardiovascular benefit or harm have returned inconsistent results 1
• Advise patients to report chest pain, shortness of breath, dizziness, or transient loss of consciousness during follow-up 1

Inform patients there is no evidence linking testosterone therapy to prostate cancer development: 1

• For men with history of prostate cancer, there is inadequate evidence to quantify the risk-benefit ratio 1
• The decision to commence therapy in men with in-situ prostate cancer on active surveillance or previously treated prostate cancer should be made with caution 1

When to Stop Testosterone Therapy

Discontinue testosterone if: 1

• Patients do not experience symptomatic relief after reaching target testosterone levels (450-600 ng/dL)
• Patients remain testosterone deficient in the setting of symptom/sign improvement
• Severe adverse effects develop (erythrocytosis, cardiovascular symptoms, prostate concerns)

Fertility Preservation Alternative

For men wishing to preserve fertility with low/normal LH levels, consider alternatives to testosterone: 2

• Selective estrogen receptor modulators instead of testosterone therapy 2
• Gonadotropin therapy (combination of hCG and FSH) 2