Lupron for Endometriosis: Side Effects and Add-Back Therapy

Lupron Depot (leuprolide acetate) is a shot for endometriosis pain and lesions. It is a GnRH agonist, and it switches off the hormone signal to your ovaries, so your estrogen drops to a very low level. Endometriosis tissue depends on estrogen, so with less estrogen it becomes inactive and the pain usually goes down.

Your doctor may add a daily hormone tablet, called add-back therapy, to protect your bones and ease hot flashes. This guide covers the flare in the first weeks, the side effects, add-back therapy, the 12-month limit, and what to write down each week. It is general information and not medical advice. Your own doctor decides what is right for you.

For a comparison of all the main treatments, see our guide to endometriosis treatment options. This page is only about Lupron Depot for endometriosis.

What Lupron is and how it works

GnRH is the hormone from your brain that starts the chain that ends with your ovaries making estrogen. Leuprolide acts like GnRH, but it acts all the time. A monthly shot causes a short burst of hormones at first, then a long shutdown of the signal to the ovaries. The effect wears off after you stop.

A doctor or nurse gives the shot into a muscle. There are two forms for endometriosis: 3.75 mg once a month, and 11.25 mg once every 3 months. The two release the medicine in different ways, so one cannot replace the other. If you miss an appointment, call your clinic right away to book a new one.

Because of the side effects, GnRH agonists are a second-line choice. Doctors usually offer them after hormonal birth control or progestogens have not helped. Doctors can start it before a diagnosis by surgery. In a 3-month trial in 100 people with pelvic pain and suspected endometriosis, pain went down more on leuprolide than on a dummy shot (placebo).

The flare in the first weeks

Your symptoms can get worse before they get better. After the first shot, sex hormones rise above your usual level for a short time, and pain can increase in the first days. This flare should settle as treatment goes on. Hormone levels can stay raised for the first few weeks, so your doctor may want to hear about any new or worse symptoms in that time.

You may still bleed in the first month. In the trials, 74% had no periods after the first month and 98% after the second. Most of the others had only light bleeding or spotting.

How long before it helps

Plan on about 2 months. In a 1-year study of 201 people, pelvic pain scores were clearly lower by week 8 in every group, with or without add-back.

Period pain improves the most, because periods mostly stop. In the two add-back studies, 99% to 100% had period pain at the start and 4% to 9% at the end of treatment. Pelvic pain between periods improved less: 56% to 66% still had some at the end, though it was milder. Pain during sex followed the same pattern.

Common side effects

Most of the common side effects come from low estrogen. The rates below come from the FDA label. They are from two trials in 166 people with endometriosis on Lupron alone for 6 months, and 31 on placebo:

Sleep problems are common too. In one add-back trial, 31% on Lupron alone had trouble sleeping, against 13% who also took add-back. Hair thinning is on the label as a less common effect, in fewer than 5% on Lupron alone.

Depression can start or get worse on GnRH agonists, and the risk is higher if you have had depression before. Tell your doctor before you start if you have had depression, and tell them at once if your mood drops.

Lupron is not birth control. Your doctor may check that you are not pregnant before you start, because the medicine may harm a baby. Use a non-hormonal method such as condoms, and keep using it even when your periods stop.

Add-back therapy

Add-back therapy is a small daily dose of hormone that you take with Lupron. With Lupron it is norethindrone acetate 5 mg, a progestin tablet taken once a day, and it cuts bone loss and hot flashes while Lupron keeps working on the pain. Some doctors use a combined estrogen and progestin add-back instead.

The difference in hot flashes is large. After about 6 months (week 24) of a 1-year trial, 86% on Lupron alone still had hot flashes, against 58% on add-back. The worst day averaged about 6 hot flashes on Lupron alone and about 2 on add-back.

Bone density and the 12-month limit

Low estrogen thins your bones. Some of this bone loss may not come back after you stop, and this is why treatment has a time limit. Here is the average change in spine bone density in the add-back trials:

A year after stopping, the Lupron-alone group was still about 2.2% below where it started. The add-back groups were close to their starting level. Everyone in these trials also took a daily calcium supplement. Ask your doctor whether you should take calcium too.

The label sets these limits:

• First course. Up to 6 months, with or without add-back.
• Second course. If symptoms come back, up to 6 more months, only with add-back. Your doctor checks your bone density with a scan before a second course.
• Total. No more than 12 months in all.

The risk is higher if you drink more than 3 units of alcohol a day, smoke, have a strong family history of osteoporosis, or take long-term steroids or seizure medicines. Tell your doctor about any of these before you start.

What to track week by week

A short daily note helps you and your doctor answer one question: is the pain relief worth the side effects? Write down one week of your usual symptoms before the first shot if you can. It gives you something to compare with. For help with pain scores, see how to describe period pain.

• Weeks 1 and 2. Pain from 0 to 10 each day, and any bleeding. This is the flare window, so pain can go up for a few days. Note anything that feels unusual.
• Weeks 3 to 8. Hot flashes per day, sleep, headaches and mood. Keep scoring your pain and note what it stopped you doing.
• Each month. The date of your shot, your worst pain on the days you would have had a period and on other days, pain during sex, and how often you took pain relief. Less rescue medicine is a sign the treatment helps.
• Every day on add-back. Whether you took the tablet.
• Near month 6. Ask about a bone scan if a second course is possible, and bring your notes to that visit.

Endolog is a pain and symptom diary for endometriosis. You log pain, bleeding, other symptoms and notes on the days they happen, so you have a record for each review. A paper notebook works too.

When to call your doctor

Get emergency help now if you have:

• Thoughts of harming yourself. In the US, call or text 988.
• A sudden, severe headache with vomiting, vision changes or confusion, mostly in the first 2 weeks after the first shot. This can be a rare loss of blood supply to the pituitary gland.
• Swelling of your face, lips or throat, or trouble breathing.
• A seizure.
• Chest pain, weakness on one side, or slow or difficult speech.

Call your doctor soon if:

• Your mood gets low, or anxiety or mood swings get worse
• You have a rash with fever, blisters, peeling skin or mouth sores. This can be a severe skin reaction.
• You could be pregnant
• You have bone pain, or a broken bone after a small fall
• Hot flashes or poor sleep make daily life hard

Talk to your doctor at your review if:

• Your pain has not gone down after 2 to 3 months
• The side effects outweigh the relief
• You are near the 6-month mark and want to plan what comes next

For other medicines that lower estrogen or calm endometriosis, see our guides to Orilissa (elagolix) and dienogest (Visanne).

Frequently asked questions

What is Lupron used for in endometriosis?

It is used for endometriosis pain and to shrink endometriosis lesions. The same medicine is also used for prostate cancer, fibroids and early puberty, at different doses and schedules.

How long can I be on Lupron for endometriosis?

Up to 6 months for a first course, and up to 12 months in total with add-back, because of bone loss.

Does Lupron make endometriosis go away?

It treats the symptoms while you take it. Symptoms can come back after you stop, and this is why the label allows a second course with add-back.

Does Lupron cause hair loss?

It can, but it is not common. Hair loss is listed in fewer than 5% of people on Lupron alone.

When will my period come back after Lupron?

After 6 months of monthly shots, normal cycles came back in 7% after 1 month, 71% after 2 months and 95% after 3 months.

Does Lupron affect fertility later?

Fertility is lower while you are on it. After people stop, there is no evidence that their pregnancy rates are affected. If you plan a pregnancy, ask your doctor.

This article is for general information. It is not medical advice and does not replace advice from your own doctor, who decides what treatment is right for you. If you think you have an emergency, call 911.