Can Lupron (leuprolide) cause leg weakness?

Lupron (Leuprolide) and Leg Weakness

Yes, Lupron (leuprolide) can cause leg weakness as a side effect, particularly when it contributes to temporary bone pain or potentially as part of a neurological adverse reaction.

Mechanism and Evidence

The FDA drug label for leuprolide explicitly states that patients may experience a temporary increase in bone pain during the first few weeks of treatment 1. This bone pain can manifest as leg weakness in some patients. More concerning, the label mentions that "isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications" 1.

While leg weakness is not specifically listed as a common side effect, it can occur through several mechanisms:

1. Initial testosterone surge effect: Leuprolide initially causes increases in serum testosterone levels before suppression occurs, which can temporarily worsen symptoms 1

2. Neurological complications: In rare cases, spinal cord compression can occur, which may directly cause leg weakness 1

3. Musculoskeletal effects: Prolonged use may contribute to bone mineral density loss, potentially leading to weakness

Clinical Approach to Leg Weakness in Patients on Lupron

Assessment Algorithm:

1. Determine onset and progression:

   • Acute onset (days to weeks after initiation): Likely related to initial hormone surge
   • Gradual onset (months to years): Consider bone density loss or other mechanisms

2. Evaluate severity:

   • Mild weakness: Can often continue medication with monitoring
   • Moderate to severe weakness: Consider temporary hold and investigation

3. Rule out serious complications:

   • Spinal cord compression: Requires immediate MRI if suspected
   • Ureteral obstruction: Consider urological evaluation

Management Recommendations:

For mild to moderate leg weakness:

• Symptomatic management with analgesics for associated pain
• Monitor for progression
• Consider calcium and vitamin D supplementation if on long-term therapy

For severe or progressive leg weakness:

• Temporarily discontinue leuprolide
• Urgent neurological evaluation
• MRI of spine to rule out compression
• Consider alternative hormonal therapies if weakness persists

Special Considerations

• Patients with pre-existing neurological conditions: Higher risk of developing or worsening leg weakness
• Long-term therapy: Monitor for osteoporosis which can contribute to weakness
• Elderly patients: May have less physiological reserve and experience more pronounced weakness

Prevention Strategies

• Baseline strength assessment before initiating therapy
• Periodic monitoring of bone mineral density for patients on long-term therapy
• Early intervention for any symptoms of weakness

Patients experiencing leg weakness while on Lupron should report this symptom promptly to their healthcare provider, as it may require adjustment of therapy or further investigation to rule out serious complications.