Side Effects of Lupron (Leuprolide)
Lupron (leuprolide) causes numerous significant side effects including initial testosterone surge with potential symptom worsening, hot flashes, bone pain, sexual dysfunction, and risk of cardiovascular complications. 1
Initial Hormone Effects and Flare Phenomenon
- Initial hormone surge: Leuprolide initially causes increases in testosterone levels before suppression occurs 1
- Symptom flare: 4-29% of patients experience temporary worsening of symptoms during the first few weeks of treatment 2
- May include bone pain that requires symptomatic management
- Can cause ureteral obstruction or spinal cord compression in rare cases, potentially leading to paralysis with risk of fatal complications 1
Common Side Effects
Vasomotor Symptoms
- Hot flashes and sweating (very common) 3
- Can be severe enough to be "unbearable" for some patients
Musculoskeletal Effects
- Bone pain (especially during initial treatment)
- Risk of decreased bone mineral density with long-term use
- Joint stiffness and joint swelling
Sexual and Reproductive Effects
- Impotence/erectile dysfunction (occurs in most recipients) 2
- Decreased libido
- Testicular atrophy in males
- Amenorrhea in females
- Infertility (reversible after discontinuation in most cases) 4
Neuropsychiatric Effects
- Sleep disorders 3
- Headache
- Mood changes including depression
- Rare cases of pseudotumor cerebri with visual disturbances 3
Serious Adverse Effects
Cardiovascular Effects
- Increased risk of cardiovascular events (less significant than with estrogen therapy but still present) 2
- Potential for QT prolongation
Hypersensitivity Reactions
- Rare cases of hypersensitivity vasculitis/serum sickness 5
- Urticaria and angioedema
- Anaphylactoid reactions (rare but potentially severe)
Neurological Complications
- Rare reports of pseudotumor cerebri with papilledema and visual disturbances 3
- Can lead to temporary or permanent visual impairment if not recognized
Monitoring Recommendations
- Periodic monitoring of testosterone and PSA levels in prostate cancer patients 1
- Regular assessment of bone mineral density with long-term use
- Careful monitoring of cardiovascular risk factors
- Ophthalmologic evaluation if visual symptoms develop during treatment 3
Special Populations
Pregnancy and Fertility
- Contraindicated in pregnancy - may cause fetal harm 1
- Effects on fertility are generally reversible after discontinuation 4
- Return to pubertal gonadotropin responses within 2-6 months after stopping treatment
- Menarche typically occurs within the first year after discontinuation if bone age is appropriate
Practical Considerations
- The depot formulation (3.75 or 7.5 mg subcutaneous or intramuscular) releases drug over 28 days and may be preferred over daily injections 2
- Consider concomitant medications to manage side effects, particularly for vasomotor symptoms
- Patients should be counseled about the potential for initial symptom flare and the importance of reporting worsening symptoms
When prescribing Lupron, it's critical to weigh these potential adverse effects against the therapeutic benefits for the specific condition being treated, and to implement appropriate monitoring strategies to detect and manage complications early.