What to Know About Endometrin Side Effects Before You Start

If you've been prescribed Endometrin (Progesterone vaginal insert) as part of your fertility treatment, you probably want to know what side effects to expect. That's completely normal — and smart. Understanding what's typical and what's a red flag can help you feel more in control during an already stressful process.

This guide covers the most common Endometrin side effects, the rare but serious ones to watch for, and when you should contact your doctor.

What Is Endometrin?

Endometrin is a vaginal insert containing 100 mg of micronized Progesterone, a hormone your body naturally produces. It's manufactured by Ferring Pharmaceuticals and is FDA-approved for progesterone supplementation as part of assisted reproductive technology (ART) treatment, such as IVF.

You typically insert it vaginally two to three times daily, starting the day after egg retrieval and continuing for up to 10 weeks. For a deeper look at what Endometrin is and how it's used, see our full guide: What Is Endometrin?

Common Side Effects

Most Endometrin side effects are mild and related to the Progesterone hormone or the vaginal route of delivery. In clinical trials, the following were reported most frequently:

• Abdominal pain — Reported in about 20% of patients. This can feel like mild cramping or general discomfort in the lower abdomen.
• Abdominal bloating — Reported in about 12% of patients. Bloating is common during ART treatment in general.
• Nausea — A frequent side effect that may overlap with early pregnancy symptoms.
• Headache — Mild to moderate headaches are common with progesterone supplementation.
• Uterine cramping — Light cramping is normal and usually not a sign of a problem.
• Constipation — Progesterone slows down the digestive system, which can lead to constipation.
• Vomiting — Less common than nausea, but it can happen.
• Tiredness and fatigue — Progesterone has a natural sedating effect. Feeling more tired than usual is expected.
• Vaginal bleeding or spotting — Light spotting can occur and is often not a cause for alarm, but always report it to your doctor.
• Urinary tract infections — Using vaginal inserts may slightly increase UTI risk.
• Vaginal discharge — A white or off-white residue from the dissolved insert is completely normal.
• Vaginal irritation — Some patients experience mild itching or irritation at the insertion site.

These side effects are generally manageable and tend to improve as your body adjusts to the medication.

Serious Side Effects

While rare, some side effects require immediate medical attention. Contact your doctor right away if you experience any of the following:

• Ovarian hyperstimulation syndrome (OHSS) — Symptoms include severe abdominal pain, swelling, rapid weight gain, difficulty breathing, and decreased urination. OHSS is related to the overall ART process rather than Endometrin alone, but Progesterone can contribute.
• Signs of a blood clot (thromboembolism) — Watch for sudden leg pain or swelling, chest pain, shortness of breath, or severe headache with vision changes. Progesterone may increase the risk of blood clots.
• Allergic reactions — Seek emergency help if you experience hives, difficulty breathing, or swelling of the face, lips, tongue, or throat.
• Severe depression or mood changes — While mild mood swings are common, significant depression, anxiety, or thoughts of self-harm should be reported immediately.
• Signs of liver problems — Yellowing of the skin or eyes (jaundice), dark urine, or persistent upper-right abdominal pain.

In rare postmarketing reports, acute pancreatitis and swallowing difficulties (dysphagia) have also been reported. These are uncommon but should be taken seriously.

Specific Populations

Age Considerations

Endometrin has not been studied in women under 18 years of age. Safety and effectiveness in this age group have not been established.

Patients With a History of Depression

If you have a history of depression, let your doctor know before starting Endometrin. Progesterone can affect mood, and your doctor may want to monitor you more closely during treatment.

Breastfeeding

Progesterone passes into breast milk. If you are breastfeeding, discuss the risks and benefits with your doctor before using Endometrin.

How to Manage Common Side Effects

Here are some practical tips for dealing with the most common Endometrin side effects:

• For bloating and constipation: Drink plenty of water, eat fiber-rich foods, and stay physically active. A mild stool softener may help — ask your doctor first.
• For nausea: Take it easy on large meals. Eating smaller, more frequent meals and avoiding strong smells can help.
• For fatigue: Progesterone naturally makes you sleepy. If possible, insert your evening dose closer to bedtime. Allow yourself extra rest during treatment.
• For vaginal discharge: The chalky residue from the dissolved insert is normal. Wearing a panty liner can help with comfort. Do not use tampons.
• For vaginal irritation: Make sure you're inserting the suppository gently using the provided applicator. If irritation persists, let your clinic know.
• For headache: Over-the-counter Acetaminophen (Tylenol) is generally considered safe during fertility treatment. Avoid NSAIDs like Ibuprofen unless your doctor says otherwise.

If any side effect becomes severe or interferes with your daily life, don't tough it out — call your fertility clinic. There may be adjustments they can make to your protocol.

Final Thoughts

Most Endometrin side effects are mild and expected during fertility treatment. Abdominal bloating, fatigue, and vaginal discharge are par for the course. Serious side effects like blood clots or severe allergic reactions are rare, but knowing the warning signs can make all the difference.

Always keep your fertility clinic informed about how you're feeling. They prescribe Endometrin regularly and can help you manage side effects or adjust your treatment if needed.

If you're having trouble finding Endometrin at your pharmacy, Medfinder can help you locate it in stock near you. And if cost is a concern, check out our guide to Endometrin savings programs and coupons.