HRT Side Effects: What the FDA Labels Actually Say

Common side effects

Rates below belong to specific brand-name products in specific trials, and they cannot be compared across products. They show the kinds of effects to expect, not a number that applies to you.

• Estradiol patch (Climara label): the most common adverse reactions, each reported by 10 percent or more of women in trials, were breast pain, upper respiratory tract infection, headache, abdominal pain, pain, and edema. The postmarketing list also includes application site reaction, changes in bleeding pattern, nausea, mood changes, and dizziness.
• Oral estradiol (estradiol tablets USP label): reported reactions include changes in vaginal bleeding pattern, breakthrough bleeding and spotting, breast tenderness or enlargement, nausea, vomiting, abdominal cramps, bloating, and an increase in blood pressure.
• Oral micronized progesterone (Prometrium label): in a 3-year placebo-controlled trial of postmenopausal women also taking conjugated estrogens, headache was reported by 31 percent versus 27 percent on placebo, breast tenderness 27 versus 6, dizziness 15 versus 9, abdominal bloating 12 versus 5, and depression 19 versus 12. Hot flashes were lower with the combination (11 versus 35 percent). The label also says progesterone may cause transient dizziness and drowsiness.

Several of these, such as breast tenderness and bleeding changes, are common when starting or changing a dose. The labels recommend the lowest effective dose and periodic reevaluation, so tell your provider if an effect does not settle. See the estradiol and progesterone pages for how each is prescribed at Gala.

What the boxed warnings say

A boxed warning is a label's most prominent warning. The current estrogen labels we reviewed include one with up to four parts:

• Endometrial cancer: estrogen used alone raises the risk of endometrial cancer in a woman with a uterus. Adding a progestogen has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Unexplained, persistent or recurring abnormal vaginal bleeding needs evaluation.
• Cardiovascular disorders: the WHI reported increased risks of stroke and deep vein thrombosis with estrogen alone, and of stroke, DVT, pulmonary embolism, and heart attack with estrogen plus progestin. The label says not to use estrogen for the prevention of cardiovascular disease.
• Breast cancer: the WHI estrogen plus progestin study reported an increased risk of invasive breast cancer.
• Probable dementia: the WHI Memory Study reported an increased risk of probable dementia in women aged 65 and older. The labels say it is unknown whether this applies to younger postmenopausal women, and not to use estrogen to prevent dementia.

The older-format estradiol tablets label we reviewed has a shorter boxed warning covering endometrial cancer and cardiovascular and other risks, including the WHI findings for heart attack, stroke, invasive breast cancer, pulmonary emboli, and DVT. All of these labels end with the same instruction: prescribe at the lowest effective dose for the shortest duration consistent with treatment goals and the individual woman's risks.

FDA's 2025 and 2026 labeling changes

On November 10, 2025, FDA announced that it was initiating the removal of the broad boxed warnings from menopausal hormone therapy products. According to that announcement, labeling will be updated to remove references to cardiovascular disease, breast cancer, and probable dementia. FDA said it was not seeking to remove the boxed warning for endometrial cancer for systemic estrogen-alone products.

On February 12, 2026, FDA announced that it had approved labeling changes for six menopausal hormone therapy products covering all four categories of HRT (combination, estrogen-alone, progestogen-alone, and vaginal estrogen), and that the risk statements related to cardiovascular disease, breast cancer, and probable dementia were removed from the boxed warning. FDA said 29 drug companies had submitted proposed changes at its request.

What this means in practice: label changes are rolling out product by product, so the wording on a specific product may be the old version or the new one. The label text we reviewed for this guide, including Climara as listed on DailyMed, still showed the older four-part boxed warning. Check the current label for your own product, and ask your provider what applies to you.

Where the WHI fits in

Most of the warning language comes from the Women's Health Initiative. According to the Prometrium label, the estrogen plus progestin trial gave daily oral conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) to postmenopausal women aged 50 to 79 (average age 63.4) and was stopped early, after an average of 5.6 years, because the increase in invasive breast cancer crossed a predefined threshold.

Two limits matter. The WHI studied one oral product and one dose, and the labels say the relevance to other doses, routes, and products is not known. It also enrolled older women, many years past menopause. The Menopause Society's 2022 position statement adds that, for most healthy symptomatic women younger than 60 and within 10 years of menopause onset, benefits outweigh risks, and that breast cancer risk does not increase appreciably with short-term use of estrogen-progestogen therapy and may be decreased with estrogen alone. Whether it fits you is an individual decision. For route differences, see our guide to estradiol patch vs pill.

When to call a doctor

Stop the medicine and get urgent care or call 911 for symptoms of a blood clot, stroke, or heart attack: sudden chest pain, shortness of breath, sudden weakness or numbness on one side, trouble speaking, sudden vision loss, or severe leg pain and swelling. The Prometrium label says to discontinue immediately if a pulmonary embolism, DVT, stroke, or heart attack occurs or is suspected, and the Climara label says to discontinue immediately if a venous clot occurs or is suspected.

Contact your provider promptly for any of the following:

• Vaginal bleeding that is unexplained, heavy, persistent, or comes back, especially after menopause
• A new breast lump or nipple discharge
• Severe headache, vision changes, or yellowing of the skin or eyes
• A skin reaction or rash where the patch is applied that does not settle
• Dizziness or drowsiness from progesterone that affects driving, or any reaction that worries you

Prometrium capsules contain peanut oil and are contraindicated for people with a peanut allergy, and the label also lists known liver disease, a history of breast cancer, and active or past clots among contraindications. Make sure your provider has your full history. See also our guide to perimenopause vs menopause.

How it works at Gala

A licensed provider reviews your online intake and prescribes only if treatment is appropriate for you. Options include estradiol as a pill or patch, progesterone, vaginal estradiol, and non-hormonal options. No insurance is required, your care team is available by message for dose adjustments, and medication ships to your home. Browse the hormone health hub or start your online menopause assessment.

Sources

1. Bayer HealthCare. Climara (estradiol transdermal system) prescribing information. NLM DailyMed.
2. ANI Pharmaceuticals. Estradiol Tablets, USP prescribing information (Northwind Health listing). NLM DailyMed.
3. Acertis Pharmaceuticals. Prometrium (progesterone) capsules prescribing information. NLM DailyMed.
4. FDA. HHS Advances Women's Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. November 10, 2025.
5. FDA. FDA Approves Labeling Changes to Menopausal Hormone Therapy Products. February 12, 2026.
6. The North American Menopause Society. The 2022 hormone therapy position statement: press release with highlights. 2022.

This article is for general information and is not medical advice. Talk to a licensed provider about your own health.