Understanding Progesterone Side Effects

Progesterone is a naturally occurring hormone in the body, and when prescribed as a medication — whether as oral capsules (Prometrium), vaginal gel (Crinone), vaginal inserts (Endometrin), or injections — it can cause side effects. The good news is that most side effects are mild and manageable. But it's important to know which ones are normal and which ones need medical attention.

If you're new to Progesterone, this guide covers what the medication does, what to expect when you start taking it, and the warning signs you shouldn't ignore.

Common Side Effects of Progesterone

These side effects are reported by many patients and are generally not dangerous. They often improve after the first few weeks as your body adjusts:

• Dizziness and drowsiness: This is one of the most common side effects of oral Progesterone. It's the main reason doctors recommend taking the capsule at bedtime.
• Headache: Mild to moderate headaches may occur, especially during the first few days of treatment.
• Breast tenderness or pain: Swelling and soreness in the breasts is a hormonal response and usually eases with time.
• Nausea and vomiting: More common with oral forms. Taking Progesterone at bedtime on an empty stomach can help reduce nausea.
• Bloating: Fluid retention and bloating are common hormonal side effects.
• Mood swings and irritability: Progesterone affects brain chemistry, which can cause mood changes in some patients.
• Fatigue: Feeling more tired than usual is common, especially at higher doses.
• Joint or muscle pain: Some patients report body aches during treatment.
• Vaginal discharge: Particularly common with vaginal gel and insert forms (Crinone, Endometrin).
• Constipation or diarrhea: Digestive changes may occur as your body adjusts.

Side Effects by Formulation

Different forms of Progesterone have somewhat different side effect profiles. Knowing what to expect from your specific formulation can help you prepare.

Oral Capsules (Prometrium and Generics)

Oral Progesterone is absorbed through the digestive system, which means it's processed by the liver. This "first-pass" effect produces metabolites that cause sedation. Common side effects include:

• Drowsiness and dizziness (most pronounced with oral form)
• Nausea
• Headache
• Breast tenderness

Important note: Prometrium brand capsules contain peanut oil. If you have a peanut allergy, tell your doctor — they'll prescribe a different formulation. Learn more about Progesterone precautions and interactions.

Vaginal Gel (Crinone) and Vaginal Inserts (Endometrin)

Vaginal forms deliver Progesterone directly to the uterus with less systemic absorption, which generally means fewer whole-body side effects. Common side effects include:

• Vaginal discharge or irritation
• Pelvic cramping or discomfort
• Bloating
• Headache

Intramuscular Injection (Progesterone in Oil)

IM injections bypass the digestive system entirely but can cause significant injection-site reactions:

• Pain, swelling, or redness at the injection site
• Abscess formation (rare)
• Allergic reactions (the oil base varies — sesame, castor, or other oils)

Serious Side Effects: When to Call Your Doctor

While rare, Progesterone can cause serious side effects that require immediate medical attention. Progesterone carries an FDA boxed warning when used with estrogen in menopausal hormone therapy, noting increased risks of cardiovascular events and breast cancer.

Call your doctor immediately or go to the ER if you experience:

• Signs of blood clots: Sudden leg pain or swelling (especially in one leg), chest pain, shortness of breath, or coughing up blood. These could indicate deep vein thrombosis (DVT) or pulmonary embolism (PE).
• Signs of stroke: Sudden numbness or weakness on one side of the body, confusion, trouble speaking, severe headache, or vision problems.
• Signs of heart attack: Chest pain or pressure, pain spreading to the arm or jaw, shortness of breath, cold sweats.
• Severe allergic reaction: Hives, swelling of the face, lips, tongue, or throat, difficulty breathing.
• Seizures: New or worsening seizure activity.
• Severe depression: Marked mood changes, suicidal thoughts, or inability to function.
• Vision changes: Sudden vision loss, double vision, or bulging eyes.
• Unexplained vaginal bleeding: Any unusual or heavy bleeding that isn't expected as part of your treatment plan.

Managing Common Side Effects

Here are practical strategies to reduce discomfort while taking Progesterone:

For Drowsiness and Dizziness

• Take oral Progesterone at bedtime — this turns the sedative effect into a sleep aid
• Avoid driving or operating machinery until you know how it affects you
• Don't drink alcohol while taking Progesterone, as it increases drowsiness

For Nausea

• Take the capsule on an empty stomach at bedtime
• If nausea persists, ask your doctor about switching to a vaginal formulation
• Eat small, frequent meals during the day

For Breast Tenderness

• Wear a supportive bra
• Apply warm or cool compresses
• This usually improves within 2-4 weeks

For Bloating

• Reduce sodium intake
• Stay hydrated
• Light exercise can help with fluid retention

For Mood Swings

• Maintain regular sleep schedules
• Exercise regularly
• Talk to your doctor if mood changes are severe — dose adjustment may help

How Long Do Side Effects Last?

Most common side effects of Progesterone improve within the first 2-4 weeks of starting treatment. Your body needs time to adjust to the hormonal changes. If side effects persist beyond a month or are significantly affecting your quality of life, talk to your doctor about:

• Adjusting your dose
• Switching to a different formulation (e.g., vaginal instead of oral)
• Trying a different treatment approach, such as alternative medications

Who Is at Higher Risk for Side Effects?

Certain groups should be especially vigilant about Progesterone side effects:

• Women over 65: Increased risk of dementia with combined estrogen/progestin therapy
• Patients with a history of blood clots: Higher risk of DVT, PE, and stroke
• Patients with liver disease: Progesterone is metabolized by the liver, so liver impairment can increase drug levels and side effects
• Patients with depression: Progesterone may worsen depressive symptoms in some individuals
• Patients with peanut allergies: Prometrium capsules contain peanut oil — this is a contraindication, not just a side effect risk

Progesterone Side Effects vs. Pregnancy Symptoms

If you're taking Progesterone as part of fertility treatment or IVF, it can be especially confusing because many Progesterone side effects mimic early pregnancy symptoms:

• Breast tenderness
• Nausea
• Fatigue
• Bloating
• Mood changes

This overlap makes it impossible to determine pregnancy based on symptoms alone during the two-week wait. Your doctor will use a blood test (beta-hCG) to confirm pregnancy — don't stop taking Progesterone based on how you feel.

The Bottom Line

Most Progesterone side effects are mild and temporary. Drowsiness, headache, breast tenderness, and nausea are the most common and usually improve within a few weeks. Serious side effects like blood clots, stroke, or severe allergic reactions are rare but require immediate medical attention.

The key is knowing what's normal and what's not. If you're concerned about side effects, talk to your doctor — and if you're having trouble finding Progesterone at your pharmacy due to the current shortage, use MedFinder to check availability near you.