Should a 36-year-old male with multiple sclerosis (MS), fatigue, obesity, and low energy, with a low free testosterone level and normal total bioavailable testosterone, be started on testosterone therapy?

Testosterone Therapy for a 36-Year-Old Male with MS, Fatigue, and Low Free Testosterone

Testosterone therapy is indicated for this 36-year-old male with multiple sclerosis who has a low free testosterone level (46.8) along with symptoms of testosterone deficiency including fatigue and low energy. 1

Diagnostic Confirmation

Before initiating treatment, it's important to verify the diagnosis of testosterone deficiency:

• The patient already has a documented low free testosterone level (46.8)
• Normal sex hormone binding globulin (SHBG) with normal total bioavailable testosterone suggests a specific pattern of hypogonadism
• The symptoms of fatigue and low energy in combination with obesity are consistent with testosterone deficiency
• Multiple sclerosis may contribute to fatigue, but testosterone deficiency can exacerbate this symptom

Pre-Treatment Evaluation

Prior to starting testosterone therapy, the following assessments should be completed:

• Hemoglobin/hematocrit (withhold therapy if hematocrit >50%) 1
• Assessment of cardiovascular risk factors 1
• PSA measurement (if patient is over 40) 1
• Fertility discussion if relevant 1
• Serum estradiol if gynecomastia or breast symptoms are present 1

Treatment Recommendation

1. Starting dose: 40.5 mg of testosterone gel 1.62% applied topically once daily in the morning to the shoulders and upper arms 2
2. Apply after showering or bathing 2
3. Titrate dose based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment 2

Dose Adjustment Algorithm

• If total testosterone >750 ng/dL: Decrease daily dose by 20.25 mg
• If total testosterone 350-750 ng/dL: No change, continue current dose
• If total testosterone <350 ng/dL: Increase daily dose by 20.25 mg 2

Target Testosterone Level

• Aim for testosterone levels in the middle tertile of the normal physiologic range (450-600 ng/dL) 1
• Use minimal dosing necessary to achieve this range 1

Expected Benefits

The patient may experience improvements in:

• Fatigue and energy levels
• Lean body mass (helpful for obesity)
• Mood and well-being
• Sexual function 1

Lifestyle Modifications

Concurrent lifestyle modifications are strongly recommended:

• Weight loss program (particularly important given the patient's obesity)
• Increased physical activity
• These interventions can potentially increase endogenous testosterone levels and enhance treatment effectiveness 1

Monitoring

1. Check testosterone levels at 14 and 28 days, then periodically thereafter 2
2. Monitor for symptomatic improvement
3. Monitor hemoglobin/hematocrit (polycythemia risk)
4. Monitor for cardiovascular symptoms
5. If no symptomatic relief after reaching target testosterone levels, consider discontinuing therapy 1

Important Precautions

• Wait 3-6 months before starting therapy if the patient has a recent history of cardiovascular events 1
• Counsel the patient that the relationship between testosterone therapy and cardiovascular events remains unclear 1
• Avoid alkylated oral testosterone formulations 1
• Testosterone gel can transfer to others through skin contact; instruct on proper application and precautions 2

Special Considerations for MS

While specific evidence for testosterone therapy in MS patients with hypogonadism is limited, low DHEA levels (a precursor to testosterone) have been associated with fatigue in progressive MS 3. Addressing testosterone deficiency may therefore provide additional benefit for MS-related fatigue beyond the standard benefits of testosterone replacement.