HRT Side Effects: What to Expect

Key Takeaways:

• HRT side effects can affect some people, but they’re usually temporary. 

• Common HRT side effects include breast tenderness, digestive issues, mood changes, and spotting.

• Side effects can depend on the type of HRT you use and the method of delivery (like a patch vs. a cream).

• Serious HRT risks are rare but can include blood clots, stroke, or certain cancers.

Hormone replacement therapy typically contains estrogen and progesterone, hormones that naturally decline during perimenopause and menopause. It works to relieve symptoms like night sweats, mood swings, and vaginal discomfort.

Like all medications, hormone replacement therapy comes with a risk of side effects. HRT side effects can vary depending on the type of therapy you use, the dose you’re taking, and how your body responds. Fortunately, you have a lot of options when it comes to HRT. Working closely with a knowledgeable provider, you should be able to find a treatment plan that works for you. 

In this guide, we’ll cover the possible side effects of estrogen and progesterone therapy so you can make an informed, confident choice.

Your HRT plan might include systemic or vaginal estrogen therapy. Systemic therapy, delivered in a pill, patch, or topical gel, enters the bloodstream, which means it can affect your whole body. 

Vaginal estrogen, on the other hand, delivers a low dose of estrogen directly to the vaginal tissues. It’s only minimally absorbed into the bloodstream, making whole-body side effects much less likely.

Not everyone experiences side effects from estrogen therapy. But for those who do, side effects are usually mild and temporary. 

Side Effects of Systemic Estrogen

Common side effects of systemic estrogen can include:

• Breast and body changes. For instance, breast tenderness, muscle tightness, or leg cramps.

• Digestive issues. This could show up as nausea, vomiting, acid reflux, constipation, diarrhea, or bloating.

• Mood or energy shifts. Some may experience nervousness, low mood, dizziness, or fatigue.

• Skin and hair changes. This can include hair loss, increased hair growth in some areas, or dark patches on the face (melasma).

• Vaginal symptoms. Some HRT patients report vaginal irritation, discharge, swelling, or changes in libido (sex drive).

• General symptoms. Other symptoms might include weight changes, cold-like symptoms, and difficulty wearing contact lenses.

Healthcare providers typically recommend waiting some time to see if side effects resolve as your body adjusts to the medication. If you continue to experience HRT side effects, your provider may recommend adjusting your dose or switching to a different form of estrogen.

Rare but more serious side effects can occur during hormone replacement therapy. Contact your healthcare provider right away if you experience:

• Signs of infection (like sore throat, fever, chills, etc.)

• Severe stomach pain, swelling, or loss of appetite

• Yellowing of the skin or eyes (jaundice)

• Bulging eyes

• Joint pain

• Severe weakness or fatigue

• Signs of an allergic reaction (rash, itching, or swelling)

Side Effects of Low-Dose Vaginal Estrogen

Vaginal estrogen therapy is designed to target vaginal and urinary symptoms — like dryness, itching, or recurrent UTIs (urinary tract infections) — without affecting the rest of the body. This means that side effects are typically localized to the vagina. 

Potential side effects include:

• Vaginal irritation

• Burning

• Itching

• Vaginal discharge or spotting 

Whole-body HRT typically combines estrogen with progesterone or progestin — unless you’ve had a hysterectomy, in which case estrogen-only therapy might be recommended.

If you’re taking systemic estrogen as part of your HRT treatment plan and you still have a uterus, your provider will prescribe progesterone as well. Progesterone works to protect the uterus from the effects of supplemental estrogen.

Like estrogen, progesterone can cause side effects. These effects are typically mild and manageable, and your provider can often adjust the dose or delivery method to improve your tolerance.

Potential side effects of progesterone include:

• Fatigue

• Mood changes, like irritability, anxiety, or depression

• Vaginal bleeding, spotting, or discharge  

• Breast tenderness

• Headaches

• Digestive issues, like nausea, diarrhea, or constipation

• Cold or flu-like symptoms, such as runny nose, sneezing, or coughing

Less common but more serious side effects can also occur. These include:

• Breast lumps

• Migraines

• Severe depression

• Dizziness, loss of coordination, or difficulty speaking

• Weakness, numbness, or swelling in the arms or legs

• Rapid heartbeat or chest pain (angina)

• Vision changes

• Seizures

• Signs of an allergic reaction (such as rash, hives, swelling, or difficulty breathing)

If you experience any of these serious side effects, contact a healthcare professional immediately.

Synthetic vs. Bioidentical Progesterone  

The form of estrogen typically used in hormone replacement therapy (estradiol) is what’s known as a bioidentical hormone. This means it’s chemically identical to the form your body naturally produces during your reproductive years. Progesterone, on the other hand, often comes in a synthetic form known as progestin.

Progestin works the same way as progesterone, but it’s not chemically identical. Some small research studies indicate that synthetic progestins may be more likely to cause side effects like headaches and mood changes than bioidentical hormones. But more research is needed on this topic. 

There is an FDA-approved bioidentical progesterone, known as micronized progesterone, that may offer a more favorable side effect profile. 

Combined HRT includes both estrogen and progesterone. This treatment is usually prescribed to those who still have a uterus. It’s typically available in the form of a pill, skin patch, or topical gel.  

Because this treatment contains both hormones, the side effects overlap with those of estrogen and progesterone alone. The intensity and combination can vary from person to person, and in many cases, side effects improve as the body adjusts.

Common side effects of combined HRT treatments include:

• Mood changes (anxiety, depression, or mood swings)

• Digestive issues (nausea, vomiting, diarrhea, bloating, changes in appetite)

• Sleep issues (insomnia, fatigue, or drowsiness)

• Headaches

• Weight fluctuations or fluid retention

• Breast tenderness

• Vaginal bleeding or spotting 

• Back pain or pelvic pain

For people with sensitive stomachs, a transdermal patch may be recommended instead of oral tablets to help minimize gastrointestinal side effects.

But, keep in mind, topical treatments like patches, gels, and sprays can come with an increased risk of skin irritation. 

Now that we’ve covered common side effects of HRT, you might be wondering about other health risks. Serious complications from HRT are rare, but your personal risk depends on your age, medical history, and the type of HRT you use.

In some research, HRT is associated with a slightly increased risk of:

• Blood clots

• Gallbladder disease

• Stroke

• Breast cancer

• Heart disease

• Endometrial cancer (if you take estrogen alone and still have a uterus)

Starting HRT within 10 years of menopause or before age 60 tends to give the most benefits while keeping risks lower. To keep risks low, providers usually start you on the smallest dose that eases your symptoms. 

If you have a higher risk of blood clots, your healthcare provider might recommend a transdermal patch instead of oral HRT.

It’s also important to keep up with your yearly mammograms to ensure any changes are caught early. 

Light spotting or irregular vaginal bleeding is fairly common in the first few months of HRT. In most cases, it’s harmless and goes away in about 6 months as your body adjusts to the medication.

Bleeding patterns often depend on the type of HRT:

• Cyclic HRT. Often used for those still menstruating, this is when you take daily estrogen plus progestogen for part of the month. Cyclic (sequential) HRT mimics a natural period, so withdrawal bleeding after each progestogen phase is normal.

• Continuous HRT. This is when daily estrogen and progestogen are taken together. It’s usually prescribed to women who are past menopause and want to avoid monthly bleeding. Light or irregular spotting can happen during the first 4 to 6 months.

If bleeding is persistent, heavy, or unusual, check in with your healthcare provider. They can go over your symptoms, help you rule out other possible causes, and adjust your treatment if needed.

Many people worry about weight changes on HRT, but most don’t experience significant weight gain from the hormones alone. Natural shifts during perimenopause and menopause — like changes in metabolism, sleep, and appetite — often play a bigger role.

Research suggests lifestyle factors such as diet, activity, daily stressors, and sleep have more impact on weight than HRT itself. In fact, some studies indicate HRT may even help prevent certain changes in body fat distribution after menopause.

You can support weight management during perimenopause with:

• Balanced meals

• Regular movement

• Stress management

• Good sleep habits

• Weight loss medications

HRT may not be a good fit for you if you:

• Currently have or previously had breast, uterine, or ovarian cancer

• Have a history of stroke or blood clots

• Have active or past liver disease

• Have uncontrolled high blood pressure (hypertension)

• Are currently pregnant (which can still occur during perimenopause)

Working closely with a healthcare provider is key. Make sure to share information about any allergies and a list of medications or supplements you’re currently taking — this helps your provider spot potential interactions and adjust your plan if needed.

HRT can bring major relief from many of the symptoms of menopause. But it’s important to be aware of potential side effects and risks.

Here’s what to keep in mind about HRT side effects:

• Side effects vary by type of hormone therapy. Estrogen and progesterone can cause headaches, breast tenderness, mood changes, digestive issues, and vaginal spotting. 

• Most side effects are mild and temporary. Many symptoms ease as the body adjusts to treatment. If you experience more serious side effects, contact your healthcare provider right away.

• Serious health risks are uncommon but worth noting. Depending on the type of HRT you’re using, these could include blood clots, stroke, gallbladder disease, and certain cancers.

Finding the right HRT approach is a personal process that involves weighing the benefits of HRT against the possible risks and drawbacks. Working with a healthcare provider who listens to your concerns can help you choose a treatment that eases symptoms while minimizing side effects.

If you’re ready to explore your options, reach out to a healthcare provider to discuss your medical history, preferences, and any questions you have. HRT can be an effective tool — but the best results come from a plan tailored to you.