Leuprolide (Lupron)

Safety Summary

Most adverse effects result from suppression of sex hormones rather than direct drug toxicity. Hot flashes are the dominant class effect: 56.7-73.3% in Vabrinty prostate cancer trials (Table 4, Vabrinty label), 35-71% of men and approximately 80% of women with endometriosis in the 1994 review (Plosker & Brogden 1994, DOI 10.2165/00003495-199448060-00008). In the Lupron Depot endometriosis label, headache, vaginitis, depression/emotional lability, nausea/vomiting, dizziness, and weight change are listed as common events. In men, impotence and decreased libido occur in virtually all sexually active patients (expected pharmacological consequences noted in Vabrinty label). Testicular atrophy reported in 5.0-7.2% across Vabrinty trials (Vabrinty label Table 4). Disease flare (symptom exacerbation from initial testosterone surge) can be serious in prostate cancer patients with bone metastases or urinary obstruction; anti-androgen cover recommended. Leuprolide 3.75mg controlled bleeding in 89% of fibroid patients but caused moderate-to-severe hot flashes in 40% vs 10-11% with ulipristal PMID 22296076. Bone mineral density loss occurs with long-term use; partially reversible after shorter courses (6 months) but potentially sustained with longer administration. Add-back therapy with norethindrone helps preserve BMD (Plosker & Brogden 1994; Lupron Depot label). Injection-site reactions (sterile abscess in 1 child) are the most frequent pediatric tolerability issue PMID 1403402. FDA FAERS data shows hot flush (9,525 reports), fatigue (5,088), injection site pain (4,854), asthenia (2,382), arthralgia (1,952), headache (1,929), weight increased (1,797) as top reported events. Vabrinty postmarketing: rare pituitary apoplexy (usually within 2 weeks of first dose), convulsions, interstitial lung disease, SJS/TEN, erythema multiforme (Vabrinty label section 6.2). ADT may increase cardiovascular risk; hyperglycemia, diabetes, and QT prolongation are labeled warnings (Vabrinty label sections 5.2-5.4). A 2026 RCT (N=100+50) showed probiotic L. reuteri NCU-37 significantly reduced leuprolide-induced perimenopausal symptoms in IVF patients PMID 41399984.