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Lupron Depot side effects

Lupron Depot side effects include hot flashes, sweats, and headaches
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By | Feb. 8, 2024 Medically reviewed by Josephine Bawab, Pharm.D.
A syringe with a pink background: Lupron Depot side effects

Key takeaways

  • Lupron Depot is used to suppress estrogen or testosterone for treating conditions like prostate cancer, endometriosis, uterine fibroids, and precocious puberty, but it can cause a range of side effects from mild to severe.

  • Common side effects of Lupron Depot include hot flashes, sweats, headaches, injection site reactions, and mood changes, with some side effects potentially becoming serious, such as bone density loss or heart issues.

  • Side effects can start within 7 to 14 days of beginning treatment, with some lasting for the duration of therapy or potentially longer, affecting patients’ quality of life and requiring close monitoring and management.

  • To minimize and manage side effects, patients should report all medications and health conditions to their doctor, attend regular checkups, maintain a healthy lifestyle, and consider add-back therapy to mitigate symptoms.

In this article:

Lupron Depot (leuprolide acetate) is a gonadotropin-releasing hormone (GnRH) agonist that can help suppress the body’s production of estrogen or testosterone if they’re causing certain issues. By reducing these hormones, injections of leuprolide can slow the growth of prostate cancer in men, treat endometriosis and uterine fibroids in women, and prevent central precocious puberty in children. 

However, altering hormone levels can affect the body and mind, so this prescription medication comes with an array of possible side effects, ranging from mild to severe. While they’re not guaranteed, it’s good to understand the potential outcomes before diving into treatment. 

Common side effects of Lupron Depot

According to clinical trials, Lupron Depot’s most common side effects are hot flashes and sweats. It may also cause the following adverse reactions:

  • Injection site reactions or pain
  • Headaches
  • General pain
  • Fatigue
  • Swelling
  • Difficulty urinating
  • Weight changes
  • Testicular shrinkage (in men)
  • Vaginal dryness, discharge, and irritation (in women)
  • Pelvic pain
  • Decreased libido
  • Nausea and vomiting
  • Dizziness
  • Acne
  • Hair loss
  • Muscle weakness
  • Breast tenderness

Lupron Headaches

Headaches are among the most common side effects of Lupron Depot. In fact, in Food and Drug Administration (FDA) trials, 32% of women who took the drug for endometriosis reported experiencing headaches. Although headaches have many causes, the study notes that those headaches might be an effect of decreased estrogen. 

RELATED: What causes headaches every day? Related conditions and treatments

Most often, headaches from Lupron aren’t a cause for concern, and you can treat them with NSAIDs or other over-the-counter (OTC) pain relievers. However, if they occur simultaneously with any of the serious side effects listed below, seek immediate medical attention. 

Serious side effects of Lupron Depot

Few people who use Lupron Depot and similar drugs experience serious health problems, but they may still occur. The following are serious side effects of Lupron Depot:

  • Allergic reaction
  • Difficulty breathing
  • Loss of bone density
  • Increased blood sugar
  • Depression and mood or behavior changes
  • Increased risk of heart attack and stroke
  • Fast, pounding, or uneven heartbeat
  • Seizures
  • Pituitary apoplexy

How soon do Lupron Depot side effects start?

Greg Marchand, MD, an OB-GYN and founder of The Marchand Institute for Minimally Invasive Surgery, says, “I have used monthly and 90-day preparations of Lupron, and I find the side effects start more quickly with the 30-day dose than the 90-day dose. With either dosage, you can expect side effects as soon as seven days after starting, but I find it is closer to the 14-day mark.”

According to the drug information published on the drug manufacturer’s website, Lupron Depot causes a temporary increase of testosterone and estrogen during the first week of treatment, which could exacerbate existing symptoms.  

How long do Lupron Depot side effects last?

Common side effects, such as hot flashes, night sweats, and breast pain, may resolve during treatment, but Dr. Marchland says, “Some patients will continue to have these symptoms the entire time they are on leuprolide therapy. Leuprolide therapy is not usually used indefinitely because of concerns about bone loss, but if it was, these symptoms would most likely completely resolve after four or five years, as they do with natural menopause.”

What are the long-term side effects of Lupron Depot?

While many side effects are short-lived, some are persistent. In one clinical trial published in 2018, 80% of patients ages 15 to 25 who received a 12-month Lupron Depot treatment, plus add-back therapy (norethindrone alone or with estrogen), reported at least one side effect that lasted longer than six months. The most common of these long-term side effects were migraines (35%), hot flashes (30%), joint pain (30%), and decreased libido (30%). 

According to the drug information published on the drug manufacturer’s website, “Thinning of the bones may occur during therapy with Lupron Depot, which may not be completely reversible in some patients.” They also note that the drug may cause or worsen depression. 

Lupron Depot interactions

Use of certain medications may alter how leuprolide works, including:

  • Antipsychotics: Combining leuprolide with drugs like mesoridazine or pimozide can increase the risk of developing a severely irregular heartbeat. This interaction is relatively rare, but a pre-existing heart disease can increase the risk.
  • Antiarrhythmics: When taken with leuprolide, drugs designed to treat heart rhythm problems, such as amiodarone, can interfere with the cardiac electrical system, increasing the risk of QT prolongation, a heart rhythm disorder that can potentially cause rapid, chaotic heartbeats. 
  • Tricyclic antidepressants: Medications like amitriptyline and clomipramine may decrease the effects of leuprolide and increase the risk of QT prolongation. 
  • Certain antifungals: The “azole” antifungals, such as ketoconazole and itraconazole, can also increase the risk of an irregular heartbeat when combined with leuprolide. 
  • Diabetes medications: Leuprolide can decrease the efficacy of certain diabetes medicines, such as canagliflozin, glyburide, and linagliptin, when taken with them.
  • Seizure medications: Leuprolide may slow down the excretion rate of drugs like clobazam and Valium, increasing their levels retained in the body. 
  • Oral steroids: When taken with Lupron Depot, certain corticosteroids, such as dexamethasone and methylprednisolone, can increase the risk of myopathy, rhabdomyolysis, and myoglobinuria.

Lupron Depot may interact with a wide range of drugs, so this isn’t a comprehensive list. Anyone considering Lupron Depot should report any medications they’re taking, both prescription and OTC, to a healthcare professional before beginning treatment. 

Safety measures while using Lupron Depot

Considering all of the side effects and drug interactions associated with Lupron Depot, safety should be a priority for anyone considering the medication. There’s no evidence that it can be habit-forming, but it’s important to discuss medical history, lifestyle, and potential risk factors with a doctor before taking it. 

Age restrictions

Since Lupron Depot-PED has proven to be effective in treating early onset puberty, it’s approved for use in children, but only as a puberty blocker. For endometriosis or advanced prostate cancer treatment, patients should be at least 18 years old. 

Pregnancy

since it can harm the fetus and cause congenital disabilities. “While premenopausal women are on GnRH agonists, the treatment usually stops ovulation and menstruation; however, pregnancies have occurred in patients on GnRH therapy, including the Depot version,” says Alexander Juusela, MD, a maternal-fetal medicine fellow at Wayne State University. “This is why a pregnancy test is mandatory prior to starting GnRH treatment in premenopausal patients.”

Nursing mothers

There’s little data on whether Lupron Depot gets excreted during breastfeeding and if it can harm an infant. Since human milk often contains medications from the mother and there’s a potential for serious adverse effects, Lupron’s manufacturer updated its prescribing information in 2018 to warn against using it in nursing mothers. 

Allergies

Anyone who is allergic or hypersensitive to GnRH agonists should not take Lupron since it may cause an anaphylactic reaction. Women with a history of asthma, sinusitis, and environmental or drug allergies have also developed asthma while taking leuprolide. Patients should seek medical attention if they experience any signs of an allergic reaction, such as a rash, itching, hives, trouble breathing, or swelling of the face, lips, or hands. 

Pseudotumor cerebri

In 2022, the FDA issued a warning for pediatric patients taking Lupron Depot PED, addressing the potential risk of pseudotumor cerebri. Literally meaning “false brain tumor,” it’s an intracranial pressure that occurs without the presence of a mass. The FDA recommends that the child’s doctor monitor closely for headaches, optic disc swelling, blurred or double vision, pain behind the eye, tinnitus, dizziness, and nausea.

Pre-existing heart conditions

Because Lupron Depot can affect the cardiac electrical system, particularly in men taking the drug for advanced prostate cancer, people with pre-existing heart problems should take caution. The drug can cause arrhythmias by prolonging the heart’s QT interval—the period when it relaxes between beats—potentially causing serious complications. Studies show that this kind of hormone therapy can increase the risk of cardiac complications in any patient, especially men with existing cardiovascular conditions.

Bone loss risk factors

According to a study published in 2015, vitamin D levels were “significantly lower in the patients using leuprolide acetate compared to the control group,” and the FDA drug label confirms that studies have demonstrated a risk of bone density loss in patients. 

In fact, the FDA concludes that someone with existing risk factors for decreased bone mineral content should not use Lupron Depot longer than three months for uterine fibroids or six months for endometriosis. These risk factors include long-term alcohol use, tobacco use, low physical activity, poor diet, certain medications, multiple myeloma, and a family history of osteoporosis. 

Depression

Because Lupron Depot may cause depression and mood changes, any patient with a history of mental health issues should discuss suspending treatment with their healthcare provider if they experience severe and persistent depression.

How to avoid Lupron Depot side effects

Sometimes, side effects might seem inevitable, and for some people, they might be. However, just like with many other medications, certain measures can help prevent side effects:

  • Report medical history, other medications, and habits to the prescribing doctor. Particular diseases, drugs, and habits can cause or worsen Lupron Depot’s side effects. Anyone with a personal or family history of cardiovascular conditions, osteoporosis, seizures, depression, or diabetes should tell their healthcare provider and seek medical advice before beginning treatment. They should also be honest about their sex life, alcohol consumption, and diet. 
  • Attend regular check-ups. Doctors know how to identify potential complications with leuprolide treatment that may cause side effects. By scheduling routine checkups, you’re giving them opportunities to find and address any issues that may arise. 
  • Exercise regularly. This is important for everyone, whether they’re taking Lupron Depot or not. However, certain studies—like this one from 2016 and this one from 2022—showed that regular aerobic and resistance exercise may ameliorate side effects and improve the quality of life in men receiving androgen deprivation therapy for prostate cancer.
  • Maintain a healthy diet. Staying hydrated and eating healthy foods can always help you feel your best. This is especially true for people who take medications that alter their hormones. The Lupron Depot for prostate cancer website recommends a plant-based diet that’s low in salt and fat. Increasing consumption of vitamin D might also help prevent bone loss.
  • Ask about add-back therapy. In women, Dr. Marchland says, “Leuprolide therapy works by bringing about an artificial menopausal state, so by adding back the hormones that are being suppressed, you can sometimes prevent menopausal symptoms without compromising the relief received,” However, he continues, “this is not always successful, and I have seen patients have endometriosis pain return or have their fibroids grow when adding estrogen or progesterone therapy to leuprolide.”

How to treat side effects of Lupron Depot

Some common Lupron Depot side effects may respond well to at-home treatments. For example, many people deal with hot flashes by exercising, wearing loose-fitting clothing, and avoiding triggers like hot showers, spicy food, alcohol, and caffeine. Headaches and general soreness may subside with OTC painkillers like ibuprofen and acetaminophen, while ice packs and anti-itch medications may work well for injection site redness, swelling, or irritation. 

However, not every leuprolide side effect is so simple. Certain serious symptoms require medical help, such as new or worsening bone pain, irregular heartbeat, depression, mood swings, difficulty breathing, blood in urine, extreme thirst, fainting, seizures, and signs of myocardial infarction (e.g., chest pain, shortness of breath, cold sweat, and fatigue) or stroke (e.g., sudden numbness, trouble speaking, dizziness, vision problems, and loss of coordination). 

Add-back therapy can also help relieve adverse effects after they begin, according to Dr. Juusela, adding that it can significantly decrease the unpleasant side effects of the drop in sex steroid hormones. She explains, “In my experience, add-back therapy with norethindrone acetate is the most effective method of managing side effects.” 

Dr. Marchand agrees. For his patients, he says, “I would begin by adding back some progesterone, and if that didn’t work, you could add some estrogen as well to reverse some of the side effects. Other medications that are nonhormonal and could also help these side effects include SSRIs, such as Lexapro (escitalopram oxalate) and Zoloft (sertraline), or the anti-seizure medication Neurontin (gabapentin).”

Bottom line: Is Lupron Depot safe?

Its side effects might seem intimidating, but Lupron Depot is typically safe when it’s prescribed by a doctor for endometriosis, symptoms of prostate cancer, or early puberty. That said, side effects can still occur in some instances, so anyone taking the medication should pay close attention to their body and be ready to contact their healthcare provider if necessary.