Lupron Side Effects: What's Normal and What's Not

Lupron (Leuprolide Acetate) is a powerful hormone therapy used for prostate cancer, endometriosis, uterine fibroids, and central precocious puberty. It works by dramatically lowering sex hormones in your body — and that comes with side effects.

Most side effects are manageable and expected. But some require immediate medical attention. This guide covers both so you know exactly what to watch for.

If you're still learning about this medication, check out our guide on what Lupron is and how it's used.

What Is Lupron? (Quick Overview)

Lupron is a GnRH agonist — a medication that initially stimulates and then shuts down your body's production of sex hormones (testosterone in men, estrogen in women). It's given as an injection, either monthly, every three months, or up to every six months depending on the formulation. For a deeper explanation, see our article on how Lupron works.

Common Side Effects

These side effects happen in a significant percentage of patients and are usually related to hormone suppression:

In Both Men and Women

• Hot flashes — The most commonly reported side effect. Affects up to 80% of patients. These can range from mild warmth to drenching sweats.
• Headache — Reported in roughly 25-30% of patients.
• Injection site reactions — Pain, redness, or bruising at the injection site is common with Lupron Depot.
• Fatigue — Feeling unusually tired or lacking energy.
• Mood changes — Depression, anxiety, irritability, and emotional swings.
• Joint and muscle pain — Achiness is common, especially in the first few weeks.
• Nausea — Usually mild and may decrease over time.
• Weight gain — Modest weight gain of 5-10 pounds is common during treatment.
• Insomnia — Difficulty sleeping, often related to hot flashes.

In Men (Prostate Cancer)

• Decreased libido and erectile dysfunction — Expected consequences of testosterone suppression.
• Bone pain — Can occur in the first 1-2 weeks due to "tumor flare" (a temporary spike in testosterone before levels drop).
• Gynecomastia — Breast tissue enlargement or tenderness.

In Women (Endometriosis/Fibroids)

• Vaginal dryness — Due to estrogen suppression.
• Decreased libido
• Spotting or changes in menstrual bleeding — Periods typically stop after 1-2 months of treatment.
• Bone density loss — Estrogen suppression accelerates bone loss. This is why Lupron for endometriosis is usually limited to six months (or used with "add-back" therapy).

Serious Side Effects — When to Call Your Doctor

These are less common but require prompt medical attention:

• Cardiovascular events — Lupron increases the risk of heart attack, stroke, and sudden cardiac death, particularly in men. Seek emergency care for chest pain, sudden weakness on one side, difficulty speaking, or severe shortness of breath.
• Tumor flare — In the first 1-2 weeks of treatment (especially for prostate cancer), Lupron temporarily raises testosterone before suppressing it. This can worsen bone pain, cause urinary obstruction, or compress the spinal cord. Your doctor may prescribe an antiandrogen (like Bicalutamide) to manage this.
• QT prolongation — Lupron can affect heart rhythm. Tell your doctor if you feel palpitations, dizziness, or fainting. This risk increases if you take other QT-prolonging medications.
• Seizures — Rare but reported. Seek immediate care if you experience a seizure.
• Severe allergic reactions — Hives, swelling of the face or throat, difficulty breathing. Call 911.
• Pituitary apoplexy — Extremely rare. Symptoms include sudden severe headache, vision changes, and vomiting. Requires emergency care.
• Hyperglycemia — Lupron can raise blood sugar. Diabetic patients should monitor glucose more frequently.

Side Effects in Specific Populations

Children (Central Precocious Puberty)

Children on Lupron Depot-PED may experience injection site reactions, headaches, and mood changes. Some emotional sensitivity is expected as hormone levels adjust. Rare but serious: seizures have been reported in pediatric patients. Regular monitoring by a pediatric endocrinologist is essential.

Pregnant or Breastfeeding Women

Lupron is Category X — it must not be used during pregnancy. It can cause fetal harm or miscarriage. Women of childbearing age should use non-hormonal contraception during treatment. Lupron is also not recommended while breastfeeding.

Older Adults

Men over 65 on Lupron for prostate cancer face higher cardiovascular risks. Bone density monitoring is also important, as both age and hormone suppression contribute to osteoporosis risk.

How to Manage Common Side Effects

You don't have to just suffer through side effects. Here are practical tips:

• Hot flashes: Dress in layers, keep your bedroom cool, avoid caffeine and alcohol. Some doctors prescribe low-dose Venlafaxine or Gabapentin for severe hot flashes.
• Bone density loss: Weight-bearing exercise, calcium (1,200 mg/day), and vitamin D (800-1,000 IU/day). Your doctor may order a DEXA scan to monitor bone density.
• Mood changes: Stay physically active, maintain social connections, and talk to your doctor if depression becomes severe. Therapy or medication adjustments may help.
• Weight gain: Regular exercise and a balanced diet. Focus on protein and fiber to stay fuller longer.
• Injection site pain: Apply ice before and after the injection. Rotate injection sites if receiving monthly doses.
• Fatigue: Light daily exercise (even walking) can actually improve energy levels over time.

If side effects become unmanageable, talk to your doctor about alternative treatments like Zoladex, Trelstar, or the oral option Orgovyx.

Final Thoughts

Lupron is an effective treatment, but it's not without tradeoffs. Most patients experience at least some side effects — hot flashes and fatigue are nearly universal. The good news is that most side effects are reversible once treatment stops.

Keep a symptom diary and bring it to your appointments. Your doctor can adjust your treatment plan, add supportive medications, or switch to an alternative therapy if needed.

If you're having trouble finding Lupron in stock, visit MedFinder to check pharmacy availability near you.