Hormone Replacement Therapy Side Effects and Risks

When people ask about hormone replacement therapy side effects, they may mean two different things: the serious risks named in the product label, and the milder day-to-day effects.

Our research for this page — FDA labeling documents, the Women's Health Initiative publications and the abstract (not the full text) of the Menopause Society's 2022 position statement — captured the serious risks in detail, but did not capture a rate for any of those milder day-to-day effects, so this page does not quote numbers for them.

A licensed provider can go through the full side-effect list in the specific product's label with you.

The serious risks the labels carry include blood clots in a vein (deep vein thrombosis), pulmonary embolism, stroke, heart attack, endometrial cancer and invasive breast cancer — and the FDA's 2025 labeling action left those warnings in the labels, as explained below.

Systemic estrogen-alone products keep a boxed warning for endometrial cancer: that is the warning class FDA did not remove.

How much risk applies to one person depends on specifics.

The Menopause Society's 2022 position statement says the risks of hormone therapy depend on its type, dose and duration, the route, the timing of when therapy starts, and whether a progestogen is taken alongside estrogen.

One scope note: this page is about menopausal hormone therapy — the estrogen and progestogen products prescribed to women.

Testosterone therapy for men has its own testosterone therapy guide.

Start where the labels start: the Women's Health Initiative.

The WHI randomized 27,347 postmenopausal women aged 50 to 79 (mean age 63) between 1993 and 1998 to estrogen plus progestin, estrogen alone, or a placebo.

FDA says the estrogen-plus-progestin trial was stopped in 2002 after an increased risk of breast cancer was reported, and the estrogen-alone trial in 2004 because of increased stroke risk and no heart-disease prevention.

FDA also notes that the participants averaged 63 years old — older than the women who typically start HRT, since the average age of menopause in the United States is 51.

The Premarin label still states what the substudies reported: increased risks of stroke, DVT (deep vein thrombosis), pulmonary embolism, heart attack and invasive breast cancer in the estrogen-plus-progestin substudy, and increased stroke and DVT in the estrogen-alone substudy.

There is a longer view too: an 18-year follow-up published in JAMA in 2017 found no association between the assigned hormone therapy and all-cause, cardiovascular or cancer mortality.

Then came the 2025 label change.

On November 10, 2025, FDA announced it was initiating removal of the boxed-warning language on cardiovascular disease, breast cancer and probable dementia from menopausal HRT labels, while keeping the boxed warning about endometrial cancer on systemic estrogen-alone products.

The same request removed the "lowest effective dose for the shortest time" recommendation from the boxed warning and added, for systemic products, consideration of starting hormone therapy for moderate-to-severe hot flashes in women under 60 or within 10 years of menopause.

Cardiovascular and breast cancer warnings remain elsewhere in the labels.

The updates roll out product by product.

Premarin's DailyMed label, effective June 4, 2026, still carried a boxed warning for endometrial cancer, cardiovascular disorders, breast cancer and probable dementia.

Claims also run in the opposite direction.

HHS's November 2025 press release said women starting HRT within 10 years of menopause may reduce cardiovascular disease risk "by as much as 50%", Alzheimer's disease by 35% and fractures by 50 to 60%.

Those are HHS statements, not label claims: HRT is not FDA-approved to prevent heart disease or dementia.

The approved uses are different — Premarin tablets, for example, are indicated for moderate-to-severe hot flashes, moderate-to-severe vulvar and vaginal atrophy due to menopause, and prevention of postmenopausal osteoporosis, among other uses.

The professional-society view: the Menopause Society's 2022 position statement says that for women younger than 60 or within 10 years of menopause who have no contraindications, the benefit-risk ratio is favorable for treating bothersome hot flashes and preventing bone loss, while starting more than 10 years after menopause or after age 60 is less favorable because absolute risks of heart disease, stroke, blood clots and dementia are higher.

Estrogen labels such as Premarin's list the situations in which the product should not be used.

The label's contraindication list includes:

• Undiagnosed abnormal genital bleeding
• Current or past breast cancer — the label names selected metastatic cases as the exception
• Estrogen-dependent cancers
• Current or past blood clots (deep vein thrombosis or pulmonary embolism)
• Stroke
• Heart attack
• Liver disease
• Inherited clotting disorders

This is the label's list for estrogen products such as Premarin tablets, not a do-it-yourself screening test.

A licensed prescriber weighs it against your medical history and against the specific product, dose and route being considered, and the label's exception language — selected metastatic breast cancer cases — describes a prescribing decision, not a self-assessment.

Clearing the list also does not settle the question.

The labels carry additional warnings beyond the contraindications — the breast cancer and cardiovascular ones among them — and the age-and-timing framework from the Menopause Society above still applies on top of it.

In the sources this research read — the FDA labeling documents, the Women's Health Initiative publications and the abstract (not the full text) of the Menopause Society's 2022 position statement — we did not find a requirement for routine hormone blood levels to diagnose menopause or to dose menopausal hormone therapy.

We also found no source establishing that saliva testing guides dosing, so treat any claim that a particular panel is mandatory with caution and ask what each test is for.

Beyond that, our research did not find a required monitoring schedule, and we will not invent one.

Which follow-up makes sense — which visits, which checks, how often — is a question for the licensed prescriber who knows your history and your exact product.

One concrete point: the FDA's 2025 labeling changes are rolling out product by product, so two products on the same shelf can carry different warnings right now.

Ask for the exact product name and its label revision date, and read the warnings section yourself before starting.

Hormone therapy decisions belong with a licensed prescriber who can see your full medical history, because every contraindication in the list above is history-dependent.

An evaluation that never asks about blood clots, cancer or abnormal bleeding has not covered the history behind the contraindication list above.

Questions worth bringing to a consultation:

• Which exact product, dose and route — and what does its current label warn about?
• How do my age and the timing since menopause change the benefit-risk balance the Menopause Society describes?
• Which of the label's contraindications or warnings apply to my history?
• What follow-up is planned, and what would prompt reassessing the therapy?

Our hormone replacement therapy guide covers what HRT is, who can prescribe at med spas and wellness clinics, bioidentical versus compounded products and how programs are priced, and the how to choose a med spa checklist covers the medical director, provider training and the consultation itself.

Read both before committing to a hormone program.