What You Should Know About Prempro 0.625/2.5 28 Day Side Effects

Every medication comes with potential side effects, and Prempro 0.625/2.5 28 Day is no exception. As a combination hormone replacement therapy (HRT), Prempro contains conjugated estrogens and medroxyprogesterone acetate — both of which can cause a range of effects in your body. The good news is that most side effects are mild and manageable. But some are serious and require immediate medical attention.

This guide covers what to expect when you start taking Prempro, which side effects are normal, which ones are warning signs, and how to manage the most common issues.

What Is Prempro 0.625/2.5 28 Day?

Prempro is a daily oral tablet used to treat moderate to severe hot flashes and night sweats caused by menopause. It's also approved to help prevent postmenopausal osteoporosis. The "0.625/2.5" refers to the dose: 0.625 mg of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate. It's designed for women who still have a uterus — the progestin component protects against endometrial overgrowth.

For a deeper look at how this medication works, see our guide: How Does Prempro 0.625/2.5 28 Day Work?

Common Side Effects

These side effects happen frequently and usually improve as your body adjusts to the medication over the first few weeks or months:

• Headache: One of the most reported side effects. Usually mild and responds to over-the-counter pain relievers.
• Breast pain or tenderness: Your breasts may feel swollen or sore, especially in the first few months. This typically decreases over time.
• Irregular vaginal bleeding or spotting: Very common when starting HRT. Breakthrough bleeding usually settles within 3-6 months. If it doesn't, tell your doctor.
• Abdominal pain or cramping: Mild stomach discomfort, bloating, or nausea can occur. Taking Prempro with food may help.
• Back pain: Some women report increased back or joint discomfort.
• Nausea: Usually mild and improves over time. Taking the tablet with a meal can reduce this.
• Bloating or fluid retention: You may notice puffiness in your hands, ankles, or feet. This is related to estrogen's effect on fluid balance.
• Mood changes: Some women experience mood swings, irritability, or feelings of depression. If mood changes are significant, talk to your doctor.
• Joint pain: Aches in the joints can occur but are generally mild.

Most of these side effects are temporary. If any of them become bothersome or don't improve after a few months, your doctor may adjust your dose or suggest an alternative medication.

Serious Side Effects — When to Call Your Doctor

Prempro carries a boxed warning (the most serious type of FDA warning) about several potentially life-threatening risks. Call your doctor immediately or go to the emergency room if you experience any of the following:

Blood Clots

Estrogen-progestin therapy increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Watch for:

• Sudden pain, swelling, warmth, or redness in one leg
• Sudden shortness of breath or difficulty breathing
• Sharp chest pain, especially when breathing deeply

Stroke

Seek emergency care if you notice:

• Sudden severe headache with no known cause
• Sudden numbness or weakness on one side of the body
• Sudden trouble speaking or understanding speech
• Sudden vision changes

Heart Attack

The WHI study found increased heart attack risk with estrogen-progestin therapy. Warning signs include:

• Chest pain or pressure
• Pain spreading to your arm, jaw, or back
• Shortness of breath, cold sweats, nausea

Breast Cancer

Long-term use of estrogen plus progestin has been linked to increased breast cancer risk. Report any of these to your doctor promptly:

• A new lump in your breast or underarm
• Changes in breast size or shape
• Nipple discharge

Other Serious Effects

• Gallbladder disease: Pain in the upper right abdomen, nausea, or vomiting
• Liver problems: Yellowing of skin or eyes, dark urine, severe fatigue
• Severe allergic reaction: Rash, hives, swelling of face or throat, difficulty breathing
• Vision changes: Sudden partial or complete loss of vision (may indicate retinal vascular thrombosis)

Specific Populations at Higher Risk

Certain groups face elevated risks when taking Prempro:

• Women 65 and older: The WHI Memory Study (WHIMS) found increased risk of probable dementia in this age group.
• Women with a history of blood clots: Prempro is contraindicated if you've had DVT, PE, stroke, or heart attack.
• Women with liver disease: Active liver problems are a contraindication.
• Pregnant women: Prempro is Category X — it should never be taken during pregnancy.
• Breastfeeding women: Estrogen may reduce milk production and is not recommended.

Your doctor should review your complete medical history before prescribing Prempro. For a full list of drug interactions to be aware of, see our dedicated guide.

How to Manage Common Side Effects

Here are some practical tips for dealing with the most frequent Prempro side effects:

• For headaches: Stay hydrated, manage stress, and use acetaminophen or ibuprofen as needed.
• For breast tenderness: Wear a supportive bra, apply a warm compress, and reduce caffeine intake.
• For nausea: Take Prempro with food or at bedtime.
• For bloating: Reduce sodium intake, stay active, and drink plenty of water.
• For mood changes: Regular exercise, adequate sleep, and stress management can help. If depression is significant, talk to your doctor about adjusting your treatment.
• For irregular bleeding: Track your bleeding pattern. Spotting in the first 3-6 months is normal. Bleeding that starts after this period or becomes heavy should be reported to your doctor.

Keep a side effect journal during your first few months on Prempro. This gives your doctor useful information at follow-up appointments and helps determine if a dose adjustment or medication change is needed.

Final Thoughts

Prempro 0.625/2.5 28 Day is an effective treatment for menopause symptoms, but it's not without risks. Understanding what to expect — both the common annoyances and the serious warning signs — helps you use this medication safely.

The key takeaway: mild side effects like headaches, breast tenderness, and spotting are normal and usually improve. But sudden symptoms like chest pain, leg swelling, vision changes, or severe headaches need immediate medical attention.

Always take Prempro at the lowest dose for the shortest time needed. Work closely with your doctor, attend your follow-up appointments, and don't hesitate to speak up if something doesn't feel right.

For more about this medication, visit: What Is Prempro 0.625/2.5 28 Day?