Lupron Depot is AbbVie's brand of leuprolide acetate, a synthetic nine-amino-acid analogue of gonadotropin-releasing hormone (GnRH), in a slow-release injection. Given once, it stimulates the pituitary; given continuously, it shuts the pituitary's signal down, and the ovaries or testes stop making most of their hormone. Every side effect below follows from one of those two phases. Peptide Lexicon explains the molecule in its leuprolide entry.
The US labels split by indication, and so does this page, because the side effects of the same molecule look very different in a 70-year-old man with prostate cancer, a 30-year-old woman with endometriosis and a 7-year-old with early puberty. Other uses are off-label; this page reports only what the labels record. Nothing here is a recommendation; any change on treatment is a question for the treating specialist.
The labels this page reads
| Label | Indication | Doses | Effective date |
|---|---|---|---|
| Lupron Depot (NDA 019732/020517) | Advanced prostate cancer | 7.5 mg monthly, 22.5 mg 3-monthly, 30 mg 4-monthly, 45 mg 6-monthly | 15 March 2026 |
| Lupron Depot 3.75 mg (NDA 020011) | Endometriosis; fibroids with anaemia before surgery | 3.75 mg monthly | 18 September 2025 |
| Lupron Depot-PED (NDA 020263) | Central precocious puberty | 1-, 3- and 6-month doses | 14 November 2025 |
Prostate cancer: the men's tables
The adverse-reaction tables come from small open-label trials. The figures are the share of men reporting each reaction during treatment.
| Reaction | 7.5 mg monthly (n = 56) | 22.5 mg 3-monthly (n = 94) | 45 mg 6-monthly (n = 151) |
|---|---|---|---|
| Hot flashes / sweats | 57.1% | 58.5% | 58.9% |
| General pain | 23.2% | 26.6% | — |
| Injection-site reaction or pain | under 5% | 13.8% | 19.2% |
| Testicular atrophy | 5.4% | 20.2% | — |
| Urinary disorders | 12.5% | 14.9% | — |
| Gastrointestinal disorders | 14.3% | 16.0% | — |
| Oedema | 14.3% | — | 5.3% (peripheral) |
| Fatigue / lethargy | — | — | 13.2% |
| Joint disorders / arthralgia | — | 11.7% | 9.3% |
| Decreased libido, impotence | 5.4% each | under 5% | — |
A dash means the label's table for that dose does not list the reaction at 5% or more. The 45 mg trial ran 48 weeks and reported both all events and those the investigator judged treatment-related; for hot flashes those were 58.9% and 58.3%, for injection-site pain 19.2% and 10.6%. Several entries — hot flashes, lost libido, impotence, testicular atrophy — the label marks as the expected effect of low testosterone rather than an unexpected reaction.
Tumour flare. Testosterone rises to roughly 50% above baseline in the first weeks before falling to castrate levels (under 50 ng/dL), in most men within four weeks. During the rise, the label warns of worsening bone pain, neuropathy, blood in the urine, bladder outlet obstruction and spinal cord compression that "may contribute to paralysis with or without fatal complications."
Endometriosis and fibroids: the women's tables
Against danazol and placebo (Table 2, two studies)
| Reaction | Lupron Depot 3.75 mg (n = 166) | Danazol (n = 136) | Placebo (n = 31) |
|---|---|---|---|
| Hot flashes / sweats | 84% | 57% | 29% |
| Headache | 32% | 22% | 6% |
| Vaginitis | 28% | 17% | 0% |
| Depression / emotional lability | 22% | 20% | 3% |
| General pain | 19% | 16% | 3% |
| Weight gain or loss | 13% | 26% | 0% |
| Nausea / vomiting | 13% | 13% | 3% |
| Decreased libido | 11% | 4% | 0% |
| Dizziness | 11% | 3% | 0% |
| Acne | 10% | 20% | 0% |
With and without add-back (Table 4, first six months). In the controlled study, 51 women took Lupron alone and 55 took it with norethindrone acetate 5 mg daily; an open-label study added 136 on the combination.
| Reaction | Lupron alone (n = 51) | Lupron + norethindrone (n = 55) | Open-label combination (n = 136) |
|---|---|---|---|
| Hot flashes / sweats | 98% | 87% | 57% |
| Headache / migraine | 65% | 51% | 46% |
| Depression / emotional lability | 31% | 27% | 34% |
| Insomnia / sleep disorder | 31% | 13% | 15% |
| Nausea / vomiting | 25% | 29% | 13% |
| Memory disorder | 6% | 2% | 4% |
At week 24, 32 of 37 women still on Lupron alone (86%) reported hot flashes in the past month, on a mean of 19 days, against 22 of 38 (58%) on the combination.
Bone: the one side effect the label measures before and after
| Lumbar-spine bone density, mean change from baseline | Lupron alone | Lupron + norethindrone (controlled) | Lupron + norethindrone (open-label) |
|---|---|---|---|
| On treatment, week 24 | −3.2% | −0.3% | −0.2% |
| On treatment, week 52 | −6.3% | −1.0% | −1.1% |
| 8 months after stopping | −3.3% | −0.9% | −0.6% |
| 12 months after stopping | −2.2% | −0.7% | +0.1% |
Source: Lupron Depot 3.75 mg label, Tables 9 and 10. Follow-up numbers are small (16 women in the Lupron-only arm at 12 months). The label's response is structural: total treatment with add-back "should not exceed 12 months," retreatment is not to happen without add-back, bone density is to be assessed before retreatment, and the label states that some loss "may not be reversible." It names alcohol, smoking, a family history of osteoporosis and long-term anticonvulsant or corticosteroid use as additional risks.
Central precocious puberty: the children's table
The Lupron Depot-PED label pools 421 children on the 1-month dose. Reactions in at least 2%: injection-site reactions including abscess 9% (mostly mild or moderate), emotional lability 5%, headache 3%, general pain 3%, acne or seborrhoea 3%, rash including erythema multiforme 3%, vaginitis or vaginal bleeding or discharge 3%, and vasodilation 2%. The label also warns that signs of puberty, including vaginal bleeding, can briefly increase in the first weeks, from the same initial surge that causes tumour flare in men.
The class warnings on the current labels
| Warning | Where it appears | What the label says |
|---|---|---|
| High blood sugar, diabetes, raised lipids, fatty liver | Prostate label | GnRH agonists "may lead to" these; monitor glucose or HbA1c and lipids |
| Heart attack, sudden cardiac death, stroke | Prostate label | Increased risk reported in men; "appears low based on the reported odds ratios" |
| QT prolongation | Prostate label | Androgen deprivation may prolong QT; consider ECG and electrolyte monitoring |
| Convulsions | Prostate and PED labels | Post-marketing reports, with and without prior risk factors, including with bupropion and SSRIs |
| Severe skin reactions (SJS/TEN, DRESS, AGEP) | All three labels | Interrupt if suspected; stop permanently if confirmed |
| Depression | 3.75 mg label | May occur or worsen; refer new or worsening depression |
| Psychiatric events (crying, irritability, anger, aggression) | PED label | Monitor for new or worsening symptoms |
| Pseudotumor cerebri | PED label | Raised intracranial pressure reported in children on GnRH agonists; headache, papilloedema, blurred vision |
| Embryo-fetal toxicity | Prostate and 3.75 mg labels | May cause fetal harm; the 3.75 mg label requires non-hormonal contraception |
The prostate label's post-marketing list adds mood swings, depression, rare suicidal ideation and attempts, rare pituitary apoplexy and rare serious drug-induced liver injury.
What FDA's reports show
openFDA's adverse event data (FAERS, updated 28 October 2026) returns 79,720 reports naming leuprolide in any brand, including Eligard and generics. The leading terms are hot flush (9,645), an intercepted product-preparation error (9,496), death (8,766), syringe issues (7,916) and device leakage (6,393). Two cautions: reports have no denominator and are not confirmed effects, and in a population treated for advanced cancer, "death" mostly records the disease. The large device and preparation counts reflect the mixing step that depot injections require.
What the labels do not answer
- Recovery beyond bone. The labels give no timeline for hot flashes, mood or libido after stopping.
- Long-term outcomes in the children's label beyond what its trials measured.
- Any off-label use. No figure on this page describes a population outside the three labels above.
Lupron is on our FDA-approved peptides census; local reactions across injectables are on peptide injection-site reactions, and the class-wide picture is on peptide side effects.
Sources
- Lupron Depot 7.5/22.5/30/45 mg prescribing information, AbbVie, effective 15 March 2026 (DailyMed setid cbc8f94e-7330-4465-05ad-16d64493a5dd); Tables 2, 3 and 5, sections 5 and 6.5.
- Lupron Depot 3.75 mg prescribing information, effective 18 September 2025 (DailyMed setid 00c486b0-bd7b-4898-834d-8c656e5e73cb); sections 1, 5, Tables 2, 4, 5, 9, 10.
- Lupron Depot-PED prescribing information, effective 14 November 2025 (DailyMed setid e99f47d2-da10-3127-ecb3-e5d942ae6e81); sections 5, 6.1, Table 2.
- All three read via the openFDA label API on 3 November 2026; application numbers from Drugs@FDA via openFDA, data updated 30 October 2026.
- FDA Adverse Event Reporting System via openFDA, query
patient.drug.openfda.generic_name:leuprolide, data updated 28 October 2026, read 3 November 2026.