10 Lupron Depot Side Effects You Should Know About

Lupron Depot (leuprolide) is an injectable medication that’s part of a group of medications known as gonadotropin releasing hormone (GnRH) agonists. GnRH agonists lower levels of certain sex hormones in the body. This includes estrogen and testosterone. Lupron Depot specifically is used to treat a number of conditions, including endometriosis and prostate cancer.

And although Lupron Depot is an effective choice for these conditions, it also carries the risk of many side effects. Some of these side effects are common and can be managed at home. But others are more serious and deserve a discussion with your healthcare provider. But what exactly should you look out for? 

What is Lupron Depot approved to treat?

Before we get to its side effects, we should discuss what conditions Lupron Depot is used to treat. As detailed in the table below, it has a number of FDA-approved uses and comes in many doses.

Regardless of what you’re taking Lupron Depot for, side effects are possible. Below, we’ll discuss 10 side effects of Lupron Depot and how to manage them.

1. Hot flashes and sweating

When estrogen levels fall, hot flashes and sweating can happen. In fact, it’s the most common side effect for all forms of Lupron Depot. It’s most common in people using it for endometriosis or fibroids. 

Non-medication strategies for managing hot flashes include regular exercise and quitting smoking.

But if natural remedies don’t work, your healthcare provider may recommend a prescription medication. They may suggest a non-hormonal option like venlafaxine (Effexor) or clonidine (Catapres) to manage hot flashes. But this would be an off-label use. 

2. Headaches and general pain

Headaches are a common side effect of Lupron Depot doses used for endometriosis and fibroids. They can occur in up to one-third of people using these forms of Lupron Depot. Headaches may occur because Lupron Depot lowers estrogen levels.

General pain is also a common side effect of all forms of Lupron Depot. But it may be most common if you're using doses used for prostate cancer. 

There are many strategies you can try at home to treat headaches and general pain. Simple tricks like staying hydrated and limiting substances that can worsen headaches (like caffeine) can help. You can also talk to your healthcare provider about trying over-the-counter (OTC) pain relievers, like acetaminophen (Tylenol) or ibuprofen (Mortin, Advil), for pain. But these aren’t the best option for everyone, so make sure to talk to your provider first.

3. Injection site reactions

Injection site reactions can happen with Lupron Depot. It’s most likely with doses used for management of prostate cancer. Injection site reactions may cause redness, swelling, or warmth. It can also cause pain or itching. You can help prevent injection site reactions by changing where you inject Lupron Depot with each dose. You can inject it in the buttock, outer thigh, or upper arm. 

To help reduce symptoms, an ice pack can relieve redness, warmth or swelling. OTC pain relievers, like acetaminophen and ibuprofen, can also help with mild pain. To relieve itching, try an OTC anti-itch medication, like diphenhydramine (Benadryl).

Injection site reactions can last 1 to 2 days after your injection. If you have a reaction that lasts longer, contact your healthcare provider. And if you have serious symptoms after an injection, like trouble breathing or swelling of the face and lips, seek emergency care.

4. Vaginal irritation

Vaginitis is an infection or inflammation of the vagina. It’s been reported in up to one-third of people using Lupron Depot for endometriosis and fibroids. 

Symptoms of vaginitis may include a change in vaginal discharge appearance and smell. You also may experience vaginal itching, burning, and rash. Contact your healthcare provider if you experience any of these symptoms. 

Vaginitis from Lupron Depot is due to “vaginal atrophy.” This occurs when you have low levels of estrogen in the body, and it can’t be treated with antibiotics or antifungal medications. So to treat vaginitis due to vaginal atrophy, your provider may recommend non-hormonal remedies, like lubricants, moisturizers, and routine sexual activity. Hormonal treatments may also be an option. These include low-dose vaginal estrogen products like tablets, creams, and rings. 

5. Mood changes

Lupron Depot may cause changes in your mood. New or worsening depression and mood swings can occur. If you have a history of depression or any mental health conditions, let your healthcare provider know. They can talk to you about the pros and cons of starting Lupron Depot. 

If you’re taking Lupron Depot and you experience new or worsening depression symptoms, contact your healthcare provider right away. Rarely, people may experience suicidal behaviors or thoughts after starting Lupron Depot.

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line. 

6. Urinary and genital problems

Urinary and genital problems are possible with Lupron Depot. They’re more common with doses used for prostate cancer. These can include:

• Erectile dysfunction

• Difficulty urinating

• Urinary tract infections

• Decrease in size of testicles

Many of these side effects occur because Lupron Depot lowers testosterone levels. Low libido (sexual desire) can also happen, but it’s more common with Lupron Depot doses used for endometriosis. And all forms of Lupron Depot can lower fertility while you’re taking it. But this may be reversible when you stop the medication.

7. Gastrointestinal problems

Gastrointestinal (GI) problems are possible with Lupron Depot. Most commonly, nausea and vomiting can occur in people using Lupron Depot for endometriosis. If you experience nausea, try eating smaller (but more frequent) meals. OTC and prescription nausea medications may also help. Talk to your healthcare provider to see which option may be best for you.

More serious GI problems can also occur. These are more likely with Lupron Depot doses used to treat prostate cancer. Examples include anorexia, trouble swallowing, or GI ulcers.

Contact your healthcare provider if you experience GI problems. If you experience serious symptoms, like extreme weight loss or blood in your stool, make sure to contact your provider right away. This can be a sign of a more serious problem, like an ulcer.

8. Initial worsening of symptoms

Lupron Depot can increase estrogen and testosterone levels when you first start using it. This can worsen your symptoms of endometriosis, fibroids, or prostate cancer initially. You might experience worsening bone pain, nerve pain, or blood in your urine over the first few weeks.

This initial worsening of symptoms can happen with all formulations of Lupron Depot. But after the first few weeks, Lupron Depot should start to improve your symptoms. If your symptoms don’t improve, talk to your healthcare provider.

9. Heart problems

There’s increased risk of heart problems in men using Lupron Depot for prostate cancer. This includes a heart attack, or cardiac arrest (your heart stopping). Having a stroke is also more likely. 

Lupron Depot can also cause an abnormal heart rhythm (arrhythmia). It can do this by lengthening what’s known as the “QT interval.” The QT interval refers to the “rest period” of your heartbeat. And it’s more likely if you also take other medications that lengthen the QT interval.

Though the risk of heart problems is rare, your healthcare provider will check whether you’re at increased risk before starting Lupron Depot. If you experience chest pain, a drooping face, or sudden difficulty speaking, seek emergency care. These may be signs of a heart attack or stroke.

10. Bone problems

Lupron Depot may affect your bones. Because Lupron Depot lowers estrogen levels, it can make your bones weaker. And this may not be reversible once you stop the medication. For this reason, Lupron Depot for endometriosis or fibroids should be used for no more than 12 months.

If you need Lupron Depot for endometriosis for more than 6 months, your healthcare provider will likely add another medication called norethindrone acetate (Aygestin) to your regimen. Norethindrone can help prevent bone loss. 

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Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She was a full-time clinical professor in the pharmacy practice department at D’Youville School of Pharmacy before subsequently joining the faculty of the pharmacy practice department at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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