Dangers of hormone replacement therapy: The latest research

The North American Menopause Society (NAMS) considers hormone replacement therapy (HRT) to be the most effective treatment for hot flashes, night sweats, and the vaginal and urinary symptoms of menopause. But for decades, the benefits of HRT came packaged with warnings about heart disease, strokes, and breast cancer that left women wondering whether the potential relief was worth it.

Many people’s fears of the dangers of HRT trace back to early 2000s research from a Women’s Health Initiative study. On average, participants were 63 years old, which is well past the average age women start menopause. Modern recommendations suggest people don’t start HRT after age 60. And the study reviewed an HRT formulation that’s no longer in use today. With all that in mind, in November 2025, the FDA stripped the strongest warnings from HRT labels. They said the initial risk was overstated and had kept women from a safe, effective treatment.

But many women are still understandably cautious about undergoing treatment. To help ease their concerns and make an informed decision about their care, we’ve gathered the latest research on HRT and its potential risks.

HRT for women: What to know about possible health concerns

Whether HRT is safe for you depends on a range of factors, including your personal and family medical history, how long you stay on treatment, and which hormones you take. However, there are four broad concerns to be aware of that researchers have identified in clinical studies:

• Breast cancer: After five years of use, combination HRT (treatment that delivers both estrogen and progesterone) results in two extra cases of breast cancer per 100 women per year. This risk rises the longer the treatment continues. Estrogen-only therapy behaves entirely differently: Data from the Women’s Health Initiative showed estrogen alone lowered breast cancer rates.
• Uterine cancer: In women who still have a uterus, taking estrogen alone can thicken the uterine lining and at least double the chance of uterine cancer. This risk rises even further after five years of use. That’s why many HRT medications also include progesterone. This hormone limits cell growth, so tumors are less likely to develop.
• Heart disease and stroke: Pills carry about a 60% higher rate of blood clots than patches or gels. This happens because estrogen taken orally passes through the liver, and the body responds by producing more proteins responsible for blood clots.

Which women should take care when starting HRT?

For some women, HRT carries more risks than benefits. A healthcare provider may suggest nonhormonal options if you have:

• A history of blood clots, strokes, or heart attacks
• Active liver or gallbladder disease
• A history of breast, uterine, or ovarian cancer
• Unexplained vaginal bleeding

NAMS states that several other relevant medical factors could increase risks, including:

• A history of smoking
• Untreated high blood pressure
• A strong family history of breast cancer 
• Certain migraine patterns 

Be honest with your provider. The more they know about your personal and family history, the better they can tailor your treatment plan.

Common side effects of HRT

The risks above are rare and slow-building. Physical side effects, on the other hand, are usually mild but more common. The most frequent ones include:

• Breast tenderness or swelling: Among the earliest physical adjustments to appear, and usually resolves within a few months
• Bloating or nausea: More common with oral estrogen and combination therapy
• Mood shifts or headaches: Frequently linked to the progesterone half of combination therapy
• Spotting or breakout of bleeding between periods: Expected in the first three to six months, especially when women take estrogen and progesterone together every day
• Weight changes: Some women also notice changes in weight or body composition as hormones rebalance. Track what you notice in a notes app or a journal. If a weight change lingers longer than six months, gets worse, or worries you, bring your notes to your provider. Often, your care team can adjust your dose or formulation to ease the issue. 

Ways to lower your risk and stay safe

A thoughtful treatment plan can lower most of the risks tied to HRT. Here are a few strategies backed up by current research:

• Start the conversation early: According to NAMS, starting HRT before turning 60 and within 10 years of your last period gives you the most favorable balance of benefits and risks. Long-term studies show no overall rise in heart disease or stroke for people who start HRT during this time.
• Choose patches or gels when clots are a concern: If blood clots run in your family, patches or gels can be a better option than pills since the medication doesn’t pass through the liver.
• Use the smallest dose to control your symptoms: Using higher than necessary doses of HRT won’t relieve symptoms any better; they’ll just increase your chance of side effects.
• Plan a yearly check-in: Weighing the pros and cons of HRT is an ongoing conversation. Schedule a review with your provider every year to confirm your plan still suits your needs. You can plan your check-in to coincide with other routine annual screenings like mammograms and blood pressure monitoring. 

Getting personalized support with Maven Clinic

Treatments have come a long way in the last few years, and many of the dangers associated with HRT are no longer something you need to worry about. But many factors influence whether HRT is the right choice for you, such as potential side effects or juggling the other challenges of menopause, like work struggles and managing self-care.

Maven Clinic's Hormone Care program is designed to close that gap. Members get virtual access to 30+ specialties, from OB-GYNs to mental health providers, with continuous support between visits, and a care plan built around your full health picture.

FAQ

Can hormone replacement cause cancer? 

Research has indicated that long-term use (typically over five years) of combined HRT leads to two extra cases of breast cancer per 100 women per year. These numbers typically return to baseline after stopping the therapy. 

For women who have had a hysterectomy and take estrogen-only HRT, studies show little to no increased risk, with some even suggesting a slight decrease. 

What are the risks of blood clots and stroke with HRT? 

HRT taken as an oral pill increases the risk of blood clots and stroke. This is because the liver processes the hormones, triggering the proteins that control clotting. To mitigate this risk, many doctors now prescribe transdermal HRT (patches, gels, or sprays) since these bypass the liver.

Is there an age at which HRT becomes too dangerous to start? 

Yes, researchers call this the "Timing Hypothesis." Starting HRT over 10 years after the onset of menopause or after age 60 significantly increases the risk of heart disease, stroke, and dementia.

Can HRT cause dementia?

According to the Alzheimer’s Society, there are many conflicting studies on whether HRT increases or decreases dementia risk. For instance, early studies found that women who began combination HRT after 65 suffered from roughly double the rate of dementia. But recent studies find no overall increase in dementia risk in women who start therapy near the time of menopause. The FDA removed mentions of dementia from boxed warnings on HRT medications in November 2025.

Are "bioidentical" hormones safer than standard HRT?

It depends on what kind. "Bioidentical" just means a hormone has the same structure as the ones your body makes. Some bioidentical hormones are FDA-approved, like estradiol patches and micronized progesterone pills. These are a common, well-studied option. Research suggests body-identical progesterone may even carry a lower breast cancer risk than older synthetic versions.

However, custom-compounded bioidenticals are hormones mixed at a pharmacy, not tested or approved by the FDA. Their doses can be off—sometimes by more than 25% in either direction—which can mean too little hormone to protect your uterine lining or too much circulating in your body. Major medical groups, including the American College of Obstetricians and Gynecologists (ACOG) and The Menopause Society, recommend FDA-approved hormones over compounded versions whenever possible.